Journal of ISSN: 2581-7388 Inno Biomedical Research and Reviews Volume 2: 1 J Biomed Res Rev 2019

Polymeric Nanoencapsulation of Indocyanine Green for Photodynamic Therapy Technique

1 Mohammadreza Saboktakin* Nanostructured Materials Synthesis Lab., NanoBMat Company, GmbH, Hamburg, Germany

Abstract Article Information

Indocyanine green(ICG) has been exploited as a photosensitizer for Article Type: Review use in cancerous phototherapy including breast, brain, and skin tumors. Article Number: JBRR123 Although ICG is of particular advantage for use in cancer phototherapy, it Received Date: 01 May, 2019 adversely tends to disintegrate in aqueous medium and such degradation Accepted Date: 10 May, 2019 can be markedly accelerated by light irradiation (photodegradation) and/ Published Date: 17 May, 2019 or heating (thermal degradation). Furthermore, ICG after administered intravenously will be readily bound with blood proteins and hence leads *Corresponding author: Mohammadreza Saboktakin, to only 2±4 min of plasmatic half-life. Among various pharmaceutical Nanostructured Materials Synthesis Lab., NanoBMat Com- polymers, poly (lactic-co-glycolic acid) (PLGA), PEG, Chitosan are the best pany, GmbH, Hamburg, Germany. Tel: + 16502689744; Email: saboktakin123(at)gmail.com biocompatibility, biodegradability, and controllability for drug release. Thisdefined review biomaterials shows that with novel FDA approvalapplications for drug of biodegradable encapsulation polymers due to its Citation: Saboktakin M (2019) Polymeric Nanoencapsu- as nanocarrier for ICG to improve of physicochemical properties of ICG lation of Indocyanine Green for Photodynamic Therapy such as Half-life. Technique. J Biomed Res Rev Vol: 2, Issu: 1 (62-76). Keywords: Biodegradable polymers, Indocyanine green (ICG), Copyright: © 2019 Saboktakin M. This is an open-access article distributed under the terms of the Creative Commons Introduction Attribution License, which permits unrestricted use, distri- Photodynamic therapy (PDT), Cancer treatment. bution, and reproduction in any medium, provided the orig- As mentioned earlier, the encapsulation of ICG in the polymeric inal author and source are credited. construct enhances its physicochemical attributes such as half-life, bioavailability, stability and pharmacokinetic characteristics, and reduces the ease of degradation. Moreover, these versatile ICG- encapsulated NIR theranostic nanoparticles also offer numerous other imaging, which facilitate them in exploring other innovative therapeutic applications.advantages such Herein, as significant we elaborate targeting on the discussionability and ofsensitivity ICG encapsulation in tumor and its delivery using various ground-breaking polymer nanocomposites with a set of examples. Among various approaches of breast cancer treatment, near-infrared (NIR)-mediated phototherapy is one of the most promising strategies for serving as a supplement to traditional cancer therapies since it can provide 1) enhanced tissue penetration toxicity to normal cells/tissues through use of targeted photosensitive agentsefficacy asand/or compared spatially with thatcontrolled operated light by visible irradiation light and [1]. 2) moderateGenerally speaking, phototherapy is carried out by hyperthermia and/or reactive oxygen species (ROS) generated from the photosensitizers under light illumination in the presence of oxygen that the former may cause thermal ablation of cancer cells (i.e., photothermal therapy; PTT), while the latter may seriously interfere cellular metabolism and thus trigger programed mechanism is utilized, the photosensitizer plays a key role in the effectivenesscell death (i.e., of phototherapy. photodynamic Indocyanine therapy; PDT) green [2,3]. (ICG) No is matter an U.S. which Food and Drug Administration (FDA)-approved tricarbocyanine dye which www.innovationinfo.org calcium phosphosilicate nanoparticles (CPNPs) and forenables use in to diagnostic absorb and purposes fluoresce such in the as regionNIR image-guided of 650±850 nm. Currently, in addition to serving as a fluorophoric agent demonstrated that small size (16 nm) ICG-encapsulating OtherCPNPs inorganic have significantly delivery systems better using contrast silica agentnanoparticles optical oncologic surgery [4], fluorescence angiography [5], and properties than free fluorophores for tumor imaging [21]. as a photosensitizer for use in cancerous phototherapy have been developed to encapsulate ICG, and the ICG–SiO2 includinglymph node breast, detection brain, of and cancer skin tumors [6], ICG [7-9] has sincebeen itexploited enables nanoparticles have the potential to be used as contrast to produce heat and ROS (i.e., singlet oxygen) upon NIR agents for optical NIR imaging as well [22]. Among these irradiation. Although ICG is of particular advantage for use in nanocarriers, micelles are one of the successful types of drug cancer phototherapy, it adversely tends to disintegrate in delivery systems for in vivo applications due to their small aqueous medium and such degradation can be markedly accelerated by light irradiation (photodegradation) and/or the reticuloendothelial system (RES) and allow for an size (approximately 10-100 nm), which reduce clearance by administered intravenously will be readily bound with blood and stabilization of ICG dye as a contrast agent in micellar proteinsheating (thermal and hence degradation) leads to only [10]. 2±4 Furthermore, min of plasmatic ICG afterhalf- systemsenhanced is EPRof particular effect [23,24]. interest. Therefore, For example, the Pluronic encapsulation F-127 life [11,12]. These circumstances seriously hinder the applicability of ICG in the clinic and thus a strategy that have been successfully demonstrated to encapsulate and stabilize(PF-127) ICGpolymeric as an NIRmicelles contrast are approvedagent for byoptical the FDAimaging and of ICG is certainly needed for ICG-mediated therapy. Nanomedicineenables to enhance may the offer aqueous a feasible stability means and for target usage efficiency of ICG systems was also investigated by Kirchherr and co-workers, without aforementioned defects since it may provide merits and[25,26]. they found Encapsulation many micellar of ICG systems within improved various the micellar optical of enhanced bioavailability, improved stability, and security properties and stability of the ICG [27]. More interestingly, Zheng et al. have recently reported a dual-functional ICG-PL- making drug carrier, polymer is often considered as the PEG agent with several unique features for optical imaging preferredfor the payload candidate [13]. since In it terms can be of manipulated the materials to tailor used the for properties and/or functionalities required by the product for combining tumor treatment and diagnosis together, [14]. Among various pharmaceutical polymers, poly (lactic- usingand photo-therapy nanovectors [28].with This ICG. may In emergesummary, as athis new editorialstrategy co-glycolic acid) (PLGA) is the copolymer of poly(lactic acid) discussed recent developments in nanocarrier ICG contrast agents for NIR optical imaging. Here just some of the areas are collected in terms of subjects and interests but it is hoped toand its poly(glycolicbiocompatibility, acid) biodegradability, and is one of and the controllability best defined biomaterials with FDA approval for drug encapsulation due Manchanda et al. [29] have recently reported the fabrication ofthat a everynovel readerpolymer will nanoparticle find something delivery of interest system to them.with andfor drugless releaseimmunogenicity, [15]. Polyethylene is frequently glycol used (PEG), for anothersurface simultaneously entrapped indocyanine green (ICG) and FDA-approved polymer with characteristics of nontoxicity PEG-coated particle in the blood circulation can be markedly for combined chemotherapy and hyperthermia. Research in modification of drug carrier since the retention time of the doxorubicin (DOX). This system has potential applications anti-HER2 ICG-encapsulated PEG- coated PLGA nanoparticles with localized hyperthermia can produce the same effect as (HIPPNPs)increased [16].for targeted Taken all phototherapy together, we of aim HER2-expressing to develop an thatour groupachieved showed by larger that doses simultaneous of chemotherapy use of ICG alone. and In DOX this breast cancer cells. The use of ICG by implantation of study, we explored the potential of dual-agent PLGA HIPPNPs instead of naked molecules is advantageous because the polymeric carrier (i.e., HIPPNP) may 1) potentially protect the entrapped ICG from degradation intracellularnanoparticles drug (ICG-DOXPLGANPs) concentrations via to overcomenanoparticle multidrug uptake. caused by external stimuli such as light, heat, and/or extreme resistance (MDR) mechanisms in cancer cells by increasing pH [17]; 2) preciously localize the therapeutic region to solvent evaporation method. The dominant processing parametersICG-DOX- PLGANPs that control were particle prepared size byand the drug O/W entrapment emulsion manyreduce of off-target reports that toxicity, ICG encapsulators, and 3) provide such accurate as (poly estimation (lactic- for the efficacy of ICG-mediated phototherapy. There are previousefficiencies formulationof ICG and DOX based were PLGAon those concentration, parameters. PVA concentration and initial drug content. We optimized our co-glycolic acid) (PLGA) nanoparticles (diameter~360 nm) and silica-polymer composite microcapsules (diameter ~0.6 Entrapment efficiency of the optimized ICG- DOX-PLGANPs nanoparticlesto 2 μm) improve are the limited molecular in size instability for in vivo of ICG tumor and imagingprolong was measured by fluorescence measurements using the dependingits plasma on half-lifetheir EPR [18,19].effects. Recently, However, several both publications of these DMSO burst release procedure. The internalization of ICG– have reported promising results using smaller nanoparticles CytotoxicityDOX– PLGANPs was by threeassessed cancer using cell linesthe wasSRB visualizedassay. The by to encapsulate ICG for in vivo imaging. For example, Zheng et nanoparticlesconfocal laser produced microscopy by optimal and fluorescence formulation microscopy.had sizes of conjugated with folic acid (FA) and demonsstrated their use asal. [20]NIR developedcontrast agents ICG encapsulated for tumor PLGA-lipid diagnosis nanoparticlesand targeted 135±2 nm, (n=3) with a low poly-dispersity index imaging. Altinoglu et al. also synthesized biodegradable (0.149±0.014, n=3) and a zeta potential of -11.67±1.8 mV. Drug loading was approximately 3% w/w for ICG and 4% w/w for DOX (n=3). Cellular uptake of ICG and DOX from ISSN: 2581-7388 63 www.innovationinfo.org containing PLGA microspheres in a hyaluronic acid (HA) gel

formulation was prepared [30]. Figure 1 multifunctional biodegradable and biocompatible poly lactic-co-glycolicRonak et al. [31] acid have (PLGA) been developednanoparticles and characterizedloaded with indocyanine green (ICG) as an optical-imaging contrast agent for cancer imaging and as a photothermal therapy agent for cancer treatment. PLGA-ICG nanoparticles (PIN)

ofwere synthesized with a particle diameter of 246±11 nm, a polydispersity index of 0.10±0.03, and ICG loading efficiency

48.75±5.48%. PIN were optically characterized with peak excitation and emission at 765 and 810±5 nm, a Figure 1: Observation of PGLA microspheres by SEM. fluorescence lifetime of 0.30±0.01 ns, and peak absorbance at 780 nm. The cytocompatibility study of PIN showed 85% cellSuccessful viability till cellular 1-mg∕ml uptake concentration of ligand of conjugated PIN. PIN by based and in vitro cell culture results demonstrated that PIN (1)prostate have cancer the great cells potential (PC3) was to also induce obtained. local Both hyperthermia phantom-

optical(i.e., temperature stability, excellent increase ofbiocompatibility 8 to 10°C) in tissuewith healthy within 5 mm both in radius and in depth; (2) result in improved serve as an image contrast agent for deep-tissue imaging in diffusecells, and optical a great tomography. targeting capability; Figure 2 (3) have the ability to Nowadays, a new technique such as photodynamic

disinfection and eliminate Enterococcus faecalis as the most prevalenttherapy (PDT) species is associated used to achievewith secondary effective endodontic root canal infections and treatment failures. Employment of an optimized nontoxic photosensitizer (PS) such as indocyanine green (ICG) is a crucial part of this technique; the current study aimed at improving ICG photodynamic properties through conjugation of ICG into nano-graphene oxide (nGO) as a new PS, to evaluate the antimicrobial effects of nGO/ICG against E. faecalis Figure 2: TEM image of presenting of morphology of PIN. of E. faecalis at a .lower The PDT concentration based on ICG, of at ICG. the Inconcentration conclusion, theloaded application in nGO, showed of nGO a assignificant a new drug reduction delivery in the system, number in treatment.ICG–DOX–PLGANPs However, in the DOX-resistant same phenomenon MESSA/Dx5 was cancer not cells was higher compared to free ICG and free DOX concentrationaddition to the (lessanti-bacterial toxicity), property,and less offerstooth otherdiscoloration. benefits such as cost beneficial outcomes due to using the lower dye observed in MES-SA and SKOV-3 cancer cell lines. The SRB cytotoxicity results show that ICG–DOX–PLGANPs are more treat endodontic infections, alone or in combination with development of drugs for intra-articular administration, The nGO/ICG-PDT could be proposed as a new approach to sustained-releasetoxic than free DOXformulations in DOX-resistant are desirable cell lines.because In it the is conventional root canal treatments [32].Figure 3 to immediate drug leakage from the joint cavity. In this study,difficult ato maintainsustained-release the effect ofpoly(lactic- conventionalco-glycolic injections acid) due Zheng et al. [33] had successfully constructed the (PLGA) microsphere formulation for intra-articular tofluorescence improve theirimage tumorguided targeting,photothermal the therapymacrophages reagents as administration containing indocyanine green (ICG) as a cell-basedbased on (WO+ICG)@PLGA)biocarriers were nanoparticles.employed for Indelivery our design, the model drug was prepared to follow its fate after intra- articular administration in rats with a real-time in-vivo carried these nanoparticles still had phagocytosis to imaging system. ICG administered as an aqueous solution tumor(WO+ICG)@PLGA cells and could nanoparticles. also secret plenty The of macrophages anti-tumor leaked from the joint cavity in a short time and was excreted cytokines for immunotherapy of carcinoma. They also further elucidated the superior solid tumor suppression release formulation was retained in the joint cavity and releasedoutside the for body 2 weeks. within Next, 1–3 d.a sustained-releaseHowever, ICG in the formulation sustained- macrophages targeting biocarriers delivery system in efficiency of the (WO+ICG)@PLGA nanoparticles loaded ISSN: 2581-7388 64 www.innovationinfo.org

Figure 3: The SEM image of the nGO.

Figure 4: The TEM images of (A) Nanorod-Bundled WO, (B) Granulated. vivo liposomes with very high spatial and temporal precision. The activating immunotherapy and photothermal therapy in results indicate that fractional photothermal leakage from vivo. The system achieved a significant antitumor effect by nanoparticles doped with Croc dye is a promising method loaded macrophages delivery system has great potential applications. Hence, suchas targeting kind of (WO+ICG)@PLGAbiocarriers loading nanoparticles drugs and imaging agents for visual-guided synergistic therapy in vivo. for a range of controlled release applications [34]. Figure 5 Figure 4 The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near- infrared dyes ICG and IR780. Separate formulations of generatedlipid−polymer clean hybrid laser-induced nanoparticles heating and (no liposomes, production each of containing1 Croc dye, absorbed strongly at 808 nm and O2 and no photobleaching of the dye). In contrast, laser-

1 produced reactive O2, leading to bleaching of the dye andinduced also heatingdecomposition of nanoparticles of coencapsulated containing payload ICG or IR780 such as the drug doxorubicin. Croc dye was especially useful as a photothermal agent for laser-controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional of thermosensitive liposomes. Additional experiments used arelease focused of laser water-soluble beam to control fluorescent leakage dye from from immobilized the interior Figure 5: TEM image of Croc/LP-hybrid-NP.

ISSN: 2581-7388 65 www.innovationinfo.org Near-infrared (NIR) laser-induced photothermal therapy imaging paradigm that uses photothermal optical coherence (PTT) uses a photothermal agent to convert optical energy tomography (PT-OCT) to detect indocyanine green (ICG)- into thermal energy and has great potential as an effective encapsulated biocompatible poly(lactic-co-glycolic) acid local, minimally invasive treatment modality for killing (PLGA) nanoparticles embedded in highly scattering tissue phantoms with high resolution and sensitivity. The ICG-loaded PLGA nanoparticles were fabricated using a nanoparticlescancer cells. To(NPs) improve encapsulating the efficacy ofsuperparamagnetic PTT, Chengcheng ironNiu et oxideal. [35] (FedevelopedO ), indocyanine poly(lactide co-glycolide)green (ICG), (PLGA) and 4 modified emulsification solvent diffusion method. With a 3 induced PTT. They fabricated a novel type of phase-shifting 20 kHz axial scan rate, PT-OCT based on spectral-domain perfluoropentane (PFP) as synergistic agents for NIR laser- ofinterferometric ICG-encapsulated configuration PLGA nanoparticles.at 1310 nm was Anused algorithm to detect effectively produce heat in response to NIR laser irradiation basedphase changeson Fourier induced transform by a 808 analysis nm photothermal of differential excitation phase forfluorescent an enhanced magnetic thermal NPs, Fe3O4/ICG@PLGA/PFPablation effect and a phase-shift NPs, that of the spectral interferogram was developed for detecting thermoelastic expansion effect, and thus, can be used as a the depth resolved localized photothermal signal. Excellent contrast difference was observed with PT-OCT between phantoms containing different concentrations of ICG- photothermalAfter in vitro agent. treatment Figure 6 of MCF-7 breast cancer cells encapsulated PLGA nanoparticles. This technique has the with Fe O4 potential to provide simultaneous structural and molecular-

3 targeted imaging with excellent signal-to-noise for various to the cells/ICG@PLGA/PFP and the formation NPs of andmany NIR microbubbles laser irradiation, with clinical applications. Photoacoustic imaging (PAI) is an ironhistology particles and electronat the edge microscopy or outside confirmed of the microbubbles. severe damage In emerging biomedical imaging technique that is now coming vivo experiments in mice with MCF-7 tumors demonstrated to the clinic. It has a penetration depth of a few centimeters that Fe O4 and generates useful endogenous contrast, particularly from ablation upon NIR laser irradiation with minimal toxicity 3 melanin and oxy-/deoxyhemoglobin. Indocyanine green to non-irradiated/ICG@PLGA/PFP tissues. Together, NPs could their results achieve indicate tumor that Fe O4 agents for human applications, which can be also used in PAI. nanotheranostic agents for tumor ablation. Hrebesh M. 3 It(ICG) is a smallis a Food molecule and Drug dye withAdministration-approved limited applications due contrast to its /ICG@PLGA/PFP NPs can be used as effective fast clearance, rapid protein binding, and bleaching effect. Subhash, et al. [36] have been described a functional

1.6

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20 1.2 1.0 15 0.8

10 0.6

Absrobance

intensity (percent) intensity 5 0.4

0.2 0 1 10 100 1000 10000 0.0 400 500 600 700 800 900 Size (d.nm) Wavelength (nm)

Figure 6: (a,b) SEM images of Fe3O4/ICG@PLGA/PFP NPs (a) 10000×; scale bar, 2 μm; (b) 70000×; scale bar, 200 nm); (c) TEM image of Fe3O4/

ICG@PLGA/PFP NPs with a large amount of black Fe3O4 NPs embedded in the spherical shell (70000×; scale bar, 200 nm); (d)size distribution of

Fe3O4/ICG@PLGA/PFP NPs with the average diameter of 289.6±67.4 nm; (e) UV-Vis-NIR absorption spectra of Fe3O4/ICG@PLGA/PFP NPs, free

ICG and Fe3O4 NPs.

ISSN: 2581-7388 66 www.innovationinfo.org

Figure 7: (a) Schematic illustration of the preparation of PLGA-RB nanoparticles. (b) Firetly luciferase catalyzing the oxidation reaction of the native substrate D-luciferin for photon emission

because of the minimally invasive delivery of enzymes and human dendritic cells with the nanoparticles and image substrates. Bioluminescence is a natural phenomenon that themEdyta in Swider vitro and et al. in [37]vivo ,showed in a multimodal that they manner. can label This primary work occurs in various organisms, such as marine organisms demonstrates the potential of combining PAI and 19F MRI for and some insects, in which visible light is produced via cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use. has been widely used in biological detection and optical chemical reactions in vivo [57,58]. Bioluminescence therapeutic potential of bioluminescence. Bioluminescence Photodynamic therapy (PDT) is emerging as a noninvasive imaging [59-61]. Recently, researchers have recognized the lightmodality to produce for a varietyreactive of oxygen cancer species treatments (ROS), [38,39].which can In photosensitizer inside the tumors. This process is not affected typical PDT, a photosensitizer is activated by external is endogenous fluorescence that can be used to activate the that luminol has anticancer and antifungal activities through depthdamage of cancer external cells light [40- in 42]. biological For deep-seated tissue. This tumors, problem the by the light penetration depth of tissue. Wang et al. reported efficiency of PDT is decreased due to the limited penetration Moreover, quantum dots have also been combined with the clinical applications. In addition, skin photosensitivity and bioluminescence resonance energy transfer (BRET) [62]. photothermalhas hindered furtherinjury are development also common of PDTconcerns in widespread from the BRET system for in vivo imaging and PDT in recent reports penetration issue to be overcome, considerable research haspatients focused receiving on the PDTdevelopment treatment of photosensitizers [43-45]. For the in light the combined with photosensitizers have been explored becausenear infrared they (NIR)can absorb range NIR [46]. photons Up-conversion and emit nanoparticles visible light have explored new approaches, for example, using Cerenkov to activate the photosensitizer for PDT [47,48]. Researchers radiation to activate a photosensitizer for effective PDT therapy[49,50]. is Alternatively, another way X-ray to overcome is currently the light widely penetration used in clinical treatment, and X-ray-activated photodynamic internal light source is an intriguing solution for the light- limitation in deep-seated tumors [51-53]. The use of an optic light sources and emitting diodes could be a viable penetration problem. For example, implanting fiber- Alternatively, bioluminescence offers an attractive strategy Figure 8: Chemical structure of Chitin and Chitosan. approach, but it still requires invasive operation [54-56].

ISSN: 2581-7388 67 www.innovationinfo.org formic and lactic acids and in hydrochloric acid solutions generation and photodynamic effect is largely unexplored. [72]. In a pH of 7 or higher, as the pH is higher than the pKa They[63-65]. show Despite effective these photodynamic progresses, therapythe BRET-activated mediated by ROS the of amine groups, chitosan becomes insoluble, rendering its biologically applications are scarce or non-existent. As poly(lactic-co-glycolic acid) (PLGA) nanoparticles were mentioned earlier, chitosan presents adequate dopedfirefly with luciferase the photosensitizer bioluminescence Rose system.Bengal (RB). Biodegradable The PLGA- RB nanoparticles were then conjugated with luciferase, including biocompatibility, biodegradability and low toxicity. Itscharacteristics biodegradability regarding is due to a biological metabolism applications by lysozyme [74]. [73], luciferin substrate. The endogenous bioluminescence served Moreover, due to its protonation in acidic media, it presents aswhich a light produced source a tofluorescent activate thesignal photosensitizer in the presence for of ROS the particularly relevant in the intestine, where there is a high imaging, and therapeutic effect in cellular assays, which amounta favourable of mucus. interaction This is actually with one mucus of the reasons [75], whichjustifying is indicatedgeneration. that They cancer evaluated cells cellwere toxicity, destroyed cellular effectively. fluorescence The tumor-bearing ICR mice, which showed that tumor growth applicationsits application in in literature specific disease is endless, conditions, including such pulmonary as colonic antitumor effect of BRET-PDT was further investigated in andinflammation. oral insulin Nevertheless,delivery as well the as the description delivery of of antibiotics chitosan approach for phototherapy of deep-seated tumors in the absencewas significantly of external inhibited. excitation. This Figure study 7 provides a promising examples. Finally, chitosan can also be found in a variety of Nanoparticles present great potential in drug delivery dietaryand small supplements genetic fragments (Lipoforte® [76-78], and just EasySlim® to mention Blocker, some applications, yet there are some issues regarding their just to name a few) for weight loss. However, the European Food Safety Authority (EFSA) considers that there is not conditions to stabilize polysaccharide (chitosan/dextran enough evidence that supports this indication. There are stability. In this study was conducted to define the assessing the cryoprotectant capacity of two sugars (sucrose sulfate, CS/DS) nanoparticles by a process of freeze-drying, evidenceother studies that that supports report it.its However,beneficial someuse on problems lowering LDL-have the solubilisation of chitosan in different acids affected alsocholesterol been described[79,80], a claimfor supplements, that EFSA found reporting to have chitosan enough nanoparticleand glucose). preparation Additionally, and it wascharacteristics. also intended Chitosan to find is if interference with certain treatments, for example, obtained by the N-deacetylation of chitin, a polymer that can be extracted from various sources (crustacean’s shells, exoskeletons of certain invertebrates – ladybugs – and the polymeranticoagulation used in therapy this experimental with warfarin work. [81] It and is also anti-epilepsy a natural cell walls of fungi, for example). It is considered the second polymer,therapy with obtained valproate from bacteria[82]. Dextran of the sulfate Leuconostoc was the genus. other It is comprised of a branched anhydroglucose backbone with However, chitin is not very versatile due to its structure and poormost solubilityabundant inpolymer many solvents.on Earth Chitin[66], after plays cellulose a role in [67]. the protection of certain animals in nature, being organized in groupsattached are sulphur present groups, for theeach latter glucosyl believed residue, to be 17% thus of the polymertotal mass being of the expected polymer. to This be meansnegatively that, charged. 2.3 sulphur Its semi-crystalline microfibrils to provide the said protection [68]. The deacetylated form of chitin is chitosan, which chemical structure can be seen in Figure 2. Dextran sulfate structure can be seen on Figure 8. mandatory(MW ~5-500 requisites kDa [83-85] for isbiomedical also reported applications. as biocompatible Studies and biodegradable [86], thus theoretically complying with Chitosan (MW ~30-190 kDa) isN the polymer obtained monomerswhen deacetylation that are surpassesdistributed 50% randomly and is throughout comprised ofthe β are scarce, even though it was widely studied in the eighties regarding the use of dextran sulfate as a component of DDS chain.(1-4)-links This is of the D-glucosamine only natural polymer and -acetyl-D-glucosamine exhibiting a cationic action, in this context, involves inhibiting the reverse for its anti-HIV activity, against HIV-1. Its mechanism of present throughout the structure of chitosan, the more transcriptase, a viral enzyme responsible for turning the deacetylatedcharacter [69]. the Due polymer to the is, fact the that more the susceptible amine groups it is are to protonation because nitrogen has an unused pair of electrons viral RNA in viral DNA that will, ultimately, be part of the host cell DNA resulting in the production of viral particles chitosan undergoes protonation, which occurs at low pH activate macrophages by establishing an interaction with [87]. Additionally, dextran sulfate has also been shown to levels,that can it easilyacquires interact a positive with charge, electrophilic thus groups.providing When the possibility to interact with negatively charged groups. This regarding the immune system, it is believed that dextran the scavenger receptor present in these cells [88]. Moreover, ability has been widely explored in drug delivery, with the sulfate induces activation of B lymphocytes even though that preparation of nanoparticles by electrostatic interaction, as aspect that is widely mentioned in studies is an anticoagulant mechanism is mediated by macrophages [89]. Another dextran sulfate [71] as counterions. Chitosan is not soluble capacity similar to heparin, even though it wasn’t studied inreported water. usingInstead, carrageenan and because [70], thetripolyphosphate amine groups (TPP) have ora induce colitis in mouse models [91,92]. Approved further [90]. Finally, dextran sulfate is used, nowadays, to easily in acidic media. The most usual solvent for its formulations containing this polymer include two EMA- logarithmic acidity constant (pKa) of ~6.5, chitosan dissolves approved orphan medicines: i) a medicine for the prevention polymer is easily protonated, it can also be dissolved in of graft rejection and its further damage on pancreatic dissolution is 1% (v/v) acetic acid. Due to the fact that the ISSN: 2581-7388 68 www.innovationinfo.org transplantation by inhibiting the activation of complement mobilisation of progenitor cells, prior to stem cell with increasing the concentration of DS. In conclusion, NPs transplantation,system and clotting through [93] anda cytokine ii) a medicine released to by promote bone formulatedwere sufficiently buccal stable mucoadhesive when kept nanoparticles at 4∘C and able (NPs) to usingcarry marrow that can guide these important cells through blood theand protectnatural protein.mucoadhesive Ji Woon Suhpolymers. and et al.The [101] natural have mucoadhesive polymers chitosan (CS) and dextran sulfate with many characteristics that can be used in drug delivery. However,stream [94]. there Dextran is still sulfate much is a work very interestingto do and, polymer more using the ionic gelation method. As the molecular weight of importantly, study possible associations with other polymers sodium salt (DS) were used to prepare mucoadhesive NPs to produce nanocarriers with a potential use in therapeutics DS decreased, the amount of mucin and the number of buccal cells adsorbed on DS increased. The CS/DS NPs ranged from the[95-97]. characteristic Chitosan extractedfunctional fromgroups Metacarcinus of CS. The magisterCS-CMC those100 to of200 CS/sodium nm in diameter. triphosphate The adhesive pentabasic interactions (TPP) of NPs; CS/ shells using demineralization with 1.5M and 2M HCl showed DS NPs with mucin were not significantly different from of TPP and BaCl2 activity to buccal cells compared to control CS/TPP NPs in ex nanoparticleembodied with were CUR. chelated The SEM with analysis five different indicated concentrations the size of vivohowever, adhesion CS/DS tests. NPs exhibitedThese results 5 times indicate greater that mucoadhesive the buccal (0.1%, 0.2%, 0.3%, 0.4% and 0.5%) and mucoadhesive properties of NPs can be improved using natural mucoadhesive polymers. A novel nanoparticle dependent.the nanoparticles The drug to below release 500 nmwas which found was to also be confirmedbest with delivery system has been developed by employing the higherby AFM. concentration The encapsulation of chelating efficiency agents was used absolutely and the drug time oppositely charged polymers chitosan (CS) and dextran vitro drug release showed antibacterial activity when conditions investigated, the weight ratio of the two polymers release was prolonging to 80th minute for all the samples. In sulfate (DS), and a simple coacervation process. Under the new granule hydrogel composites of natural biocompatible polymericethanol and chitosan acetic acid and was gelatin used (C-G) as solvent have systemprepared. [98]. The A characteristicsis identified as aof determining the nanoparticles factor controlling produced. particleParticles size, of gelatin side groups (hydroxyl and carboxyl) can attach with surface charge, entrapment efficiency and release amine groups of chitosan, which improve the interlink 223 nm mean diameter were produced under optimal conditions with a zeta potential of approximately -32.6 mV. tocrosslinking reinforce the in themechanical final nanocomposites. properties of granules, The diameter for the of TheA maximum same nanoparticle of 75% anti- formulation angiogenesis also peptide showed entrapment slow and the granuls is around 3mm to 6 mm. Furthermore, in order efficiency was achieved with a CS:DS weight ratio of 0.59:1. - first time, octa(ammonium chloride) substituted Polyhedral sustained peptide release over a period of 6 days. In contrast, Oligomeric Silsesquioxane C-G/POSS-(NH3+Cl- )8 has been peptidethe formulation release containing characteristics. a lower The ratio results of CS:DS suggest (0.5:1) thatwas andused swelling as a nanofiller behavior in ofthe hydrogels structure has of thisbeen nanocomposite. investigated in found to have reduced entrapment efficiency and more rapid The effect of C-G/POSS-(NH3+Cl )8 on mechanical stability nanoparticles can be modulated by changing ratios of two - physicochemical and release characteristics of the CS–DS three pH of 1.2, 7.4 and 9.5, respectively. Results demonstrate the coacervation process have potential as a carrier for small that the C-G/POSS-(NH3+Cl )8 granules in acidic pH has the ionic polymers. The novel CS–DS nanoparticles prepared by maximum swelling percent. The encapsulation efficiency based nanoparticles containing indocyanine green (ICG) for (EE) values- for C-G granules in three pH of 1.2, 7.4 and 9.5 hyperthermiapeptides [102]. therapy Fwu-Long and Mi imaging. [40] have ICG prepared was incorporated chitosan- whichare obtained conform 65%,with the 58% swelling and behavior 53% and of these for C-G/POSS-hydrogels. into chitosan and poly-gamma- glutamic acid self assembled According(NH3+Cl )8 to sample the obtained are 59%, results 52% from and Metronidazole 48%, respectively, (MTZ) nanoparticles using the polyelectrolyte complex method. release, the as-synthesized hydrogels may have intrinsic ability in the controlled release of drugs. The as-prepared effectiveThe ICG encapsulationtemperature elevation efficiency upon of the NIR nanoparticles laser irradiation were analysis [99]. Chitosan nanoparticles (CS NPs) exhibit good higher than 95% and the ICG-loaded nanoparticles showed physicochemicalhydrogels are characterized properties as via drug FT-IR, delivery SEM, systems. TGA and Haliza XRD laser-induced hyperthermia effect showed an enhanced (808 nm, 1.5 W/cm2). The cytotoxicity results from NIR preparative parameters on the physical characteristics and colloidalKatas and stability et al. [100] of CS NPs. have CS determined NPs were fabricated the modulation by ionic of toxicity in overcoming doxorubicin (Dox) resistance of MCF- 7/ADR cells. Pei-Ru Wei et al. [103] have designed a study for photodynamic therapy (PDT) using chitosan coated Mg– interaction with dextran sulphate (DS) prior to determination Al layered double hydroxide (LDH) nanoparticles as the of their storage stability. The smallest CS NPs of 353±23nm greendelivery (ICG) system. with Aphotoactive Food and properties Drug Administration was intercalated (FDA) with a surface charge of +56.2±1.5mV were produced when approved near-infrared (NIR) fluorescent dye, indocyanine whenCS and BSA/siRNA DS were mixed was atloaded pH 4 andinto with the ananoparticles. DS : CS mass ratioThe resultsof 0.5 : also 1. An showed entrapment that particle efficiency size ofand 98% surface was charge achieved of wasinto amineachieved modified by the LDH cross interlayers linkage byusing ion- surfaceexchange. amine The CS NPs were slightly changed up to 2 weeks when stored at efficient positively charged polymer (chitosan (CS)) coating glutaraldehyde as a spacer. The unique hybridization of groups modified on the LDH nanoparticle surface with 4∘C. Greater particle size and surface charge were obtained ISSN: 2581-7388 69 www.innovationinfo.org organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the nondiseased areas. Concerns about NP toxicity often arise becausemarrow, ofand this nonspecific RES accumulation. binding of Aggregation NPs to nontargeted can lead orto prevents the leaching and metabolization of the NP entrapment in the liver, lungs or elsewhere due to photosensitizer stabilizationin the physiological in the interlayer conditions. of LDH,The results which capillary occlusion [119]. The addition of PEG to the NP indicated that the polymer coating and the number of surface (PEGylation) can reduce many of these challenges (Figure 1B). PEG is a coiled polymer of repeating ethylene ether units with dynamic conformations (Figure 1C). In both polymer coats have a significant impact on the photo-toxicity 2–ICG nanoparticles exhibited drug-delivery and imaging applications, the addition of PEG enhancedof the nano- photo composites therapeutic [104-106].effect compared The with double uncoated layer to NPs reduces RES uptake and increases circulation time chitosan coated LDH–NH 2 2– ICG due to the enhanced protection to photosensitizers owing to passivated surfaces, and association with LDH–NHagainst photo–ICG and and thermal single layer degradations. chitosan-coated This new LDH–NH class of nontargetedversus uncoated serum counterparts and tissue [120]. proteins Aggregation is diminished, decreases organic-inorganic hybrid nanocomposites can potentially resulting in so-called ‘stealth’ behavior. The PEG chains serve as a platform for future non-invasive cancer diagnosis reduce the charge-based contact typical of proteins and and therapy. Nanoparticles (NPs) are synthetic materials small-molecule interactions. Solubility in buffer and serum with dimensions from one to hundreds of nanometers, and increases due to the hydrophilic ethylene glycol repeats and remarkable applications in biomedicine due to the unique the EPR effect is modulated due to NP size changes via

PEGylated NPs generally accumulate in the liver a half to a incorporatingway in which they polyethylene interact with glycol matter (PEG), [107,108]. with Therea larger are thirdaddition of the of amount a PEG coat of non-PEGylated [121,122]. Due NPs to and these demonstrate attributes, numbercurrently in morepreclinical than studies 35 US for FDA-approved both imaging and NPs therapy often avidity, signal enhancement and the capacity for multiple, applicationshigher tumor [124]. accumulation All NPs contain versus backgroundat least two fundamental[123]. PEG is simultaneous(Figure 9A) [109–115]. applications NPs owing have to large their payloads, unique stability,size and spatialinexpensive, components: versatile the andcore and FDA the approved corona that for interact many than molecules and many proteins, yet smaller than cells, multishell systems add further complexity, for example theyhigh surfacebehave area:volumedifferently toratio other [116]. therapies While they and are imaging bigger with the environment or solvent. While core/shell, core/ agents, affecting their in vivo applications. For example, in the solvent (Figure 9B). PEG chains modify this interface cancer tissue, NPs not only extravasate from the leaky tumor layer[125], andall stillincrease possess circulation an area intime. which Circulation NP interfaces half-time with vasculature to a higher degree than healthy tissue, but also (t½) describes blood pool residence and is the period over remain in the area by the enhanced permeability and which the concentration of circulating NPs remains above retention (EPR) effect [117]. NPs lodged in the tumor can advantages, some fundamental challenges hamper NP target,50% of but the also injected remain dose,in the analogousaffected area to (at a drug’sconcentrations half-life deploymentthen perform to signaling the clinic. and/or These therapy include [118]. uptake Despite by these the [126]. NP efficacy requires sufficient t½ to not only reach the reticuloendothelial system (RES), in which NPs are rapidly capture or drug delivery. The RES system prevents site- shuttled out of circulation to the liver, spleen or bone sufficiently above background tissue) long enough for image

specific accumulation because it removes the NPs from

Figure 9: Nanoparticle applications of Polyethylene glycol.

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Figure 10: Polyethylene glycol prevents uptake by the reticuloedothelial system. circulation, acting as a competitor to the intended target site and hydrophilic PEG reduces these complications. In addition [127]. In addition, the NPs must clear from the nontargeted to NP–RES interactions, poor t½ can also result from NP– NP interactions (i.e., aggregation). NPs aggregate primarily because the attraction between particles is stronger than optimalarea to producefor injection, imaging accumulation contrast ator targeteddosing efficiency. site, clearance The fromideal t½nontargeted is dependent areas on application.and data collection. In imaging, The 2–6 ideal h is energy have a greater tendency to aggregate as described circulation time for therapeutic NPs is longer (days) to allow the attraction for solvent [130]. NPs with a high surface repeated exposure to affected area. Unfortunately, this can also expose healthy organ systems to the drug and is the relatedby the Derjaguin-Landau- to the electrostatic Verwey-Overbeek repulsive potential (DLVO) and the theory van motivation for targeted NPs, as such systems preferentially [131,132]. For spherical NPs, the interaction potential is accumulate in the diseased area. Approaches to measuring der Waals attraction potential [133]. PEG decreases the surface energy of NPs and minimizes van der Waals attraction determinest½ vary with NP NP circulation type. When time. labeled One limitation with radionuclides, is dissociation g highly[134–135]. concentrated Aggregation solutions can be of induced NPs (less by distance solvents between of high ofcounting radionuclide of either specificfrom organNPs; systemshowever, or bloodradioactivity aliquots the(>100 NPs), mM) time ionic from strength synthesis, (shielding or NP ofpreparations solvent from with NP), a measurements may always be carried out noninvasively the amount of attraction between NPs by increasing the stericveryneutral distance (~±5 between mV) zeta them potential and increasing [136]. PEGhydrophilicity decreases [128]. Figure 9 via ether repeats forming hydrogen bonds with solvent. coupled plasma or chromatography/mass spectrometry is Measurement of t½ via fluorescence, Raman, inductively the blood pool. The RES is an immune system component, Other benefits to PEGylation include modifying the size of very specific to the NP, but requires sequential sampling of utilizing circulating macrophages and monocytes, liver nm),the particle. liver uptake The reduced increases renal and filtration EPR extravasation of particles larger may Kupffer cells and spleen and other lymphatic vessels to than 10 nm increases t½; however, at too large a size (>100 remove foreign material, such as bacteria and viruses, from can become ‘softer’ after PEGylation than the underlying decrease [137]. PEG modifies the NP flexibility and the NP Prior to NP applications, PEG was used as a nontoxic, bacteriathe body and [127]. viruses Figure have 10 theillustrates same negative how opsonin surface proteins charge material, influencing extravasation. asassociate phagocytic with foreigncells, opsonins bodies andare coatcritical its surfaceto reducing [128]. the As water-soluble dispersant/stabilizer. Also known as charge repulsion between the two systems. Next, phagocytic Carboxwax®, it is present in health and beauty aids, including cells engulf the material and transport it to the liver or spleen laxatives, toothpastes and eye drops, and is an excipient blood donations. Early work with PEGylated NPs stemmed phagocytic macrophages are permanently located in the in tablet formulations [138]. PEG stabilizes organ and liver.for degradation Known as and Kupffer excretion cells, (Figure these cells 10 A3–A4). serve asAdditional a major mostly from drug delivery [139]. One of the first reports with long t½ [129]. The PEG polymer on a NP surface on PEGylation was described by Davis and Abuchowski increasesfilter for manyt½ by typesreducing of NPs this andopsonization are a major process interference (Figure albumin[140,141], and where to liver they catalase. covalently Later, acrylic attached microspheres methoxy- PEGs (mPEGs) of 1900 and 5000 Da to bovine serum macrophages, allowing the NPs to remain in the blood pool. 10B2), thus preventing recognition by monocytes and increased t½ in vivo [142]. Li and colleagues found that Hydrophobic particles are also more vulnerable to the RES functionalized with PEG-modified human serum albumin

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75-nm latex particles remained in rat circulation 40-times therapeutic efficacy, limited side-effects, selective localized foundlonger (half-lifethat incorporation 20 min vs 13 of h) dioleoyl when coated N- (monomethoxy than uncoated treatment and reproducible properties [150,151], and hence polyethyleneglycolwith PEG larger than succinyl)5000 kDa [143].phosphotidylethanolamine Klibanov and Huang agentshave received due to theirmuch high attention absorption in recent in the years tissue-transparent [152,153]. Until (PEG-PE) into posphatidylcholine:cholesterol liposomes now, a variety of materials has been explored as PTT or PDT

NIR wavelength range, including organic fluorescent (liposomal(1:1) increased delivery t½ fromvehicle 30 formin doxorubicin) to 5 h without and increasing oncospar dyes [154], gold nanorods [155], CuS nanoparticles (NPs) leakage of the liposome interior. In the mid-1990s, Doxil® [156], polymer NPs [157], carbon nanomaterials [158], aetc. tumor, [159,160]. and inorganic However, photothermal fluorescent dyes agents may have be potentialremoved (PEG-l-asparaginase) became the first FDA-approved rapidly from the systemic circulation and lack specificity to PEGylatedNP therapeutics liposomes [143]. versus Doxilfree drug increases [144]. The doxorubicin use of PEG onbioavailability the doxorubicin nearly carrier 90-fold yields at a 1 drug week half-life from of injection 72 h with of therapeuticlong-term toxicity nanoagents due to thewith difficulty enhanced of degrading photothermal in the conversionbody [161]. Therefore,capability andexploiting ROS generation biocompatible ability and to targeted amplify introduced as an albumin-functionalized NP for delivery circulation half-life of 36 h [145,146]. Later, Abraxane® was green (ICG) is a clinical infrared imaging agent approved Thadakapally, et al. developed a novel serum stable long PTT and PDT treatments remains challenging. Indocyanine circulatingof taxane withoutpolymeric cremphor nanoparticles to enhance for curcumin drug efficiency. with a been applied in optical imaging of human vasculature, tissue andby the cells U.S. due Food to andits biocompatibility Drug Administration and (FDA),unique andoptical has albumin bound technology. polyethylene glycolalbumin- curcuminmodification nanoparticles to the well were known prepared and using novel serum nanoparticle albumin can effectively convert absorbed NIR optical energy into and poly ethylene glycol using desolvation technique. properties [162]. Due to strong absorption at 780 nm, ICG Nanoparticles were characterized for encapsulation ofheat ICG for in PTT tumor [163] phototherapy and produce is limitedROS for by PDT its [164]tendency under to excipient compatibility was determined using fourier NIR laser irradiation [165]. Nevertheless, the application transformefficiency, infrared particle spectroscopy. size and surface Physical morphology. state of the Drugdrug in the formulations was known by differential scanning Toaggregate, overcome rapid those degradation limitations, in various aqueous nanoparticle solution [64], delivery poor colorimetry. In vitro release and solubility of the drug photo-stability and non-specific binding to proteins [166]. from nanoparticles were determined. In vivo Lvet al. used a mesoporous silica (mSiO2) matrix to load ICG tissue uptake and kupffer cell uptake was determined molecules,systems have and beendemonstrated developed that to encapsulateloaded ICG displayed ICG [167]. a with optimized nano formulation in rats afterDrug intravenous release, administration. Cell viability assay was determined using ICG-loaded mesoporous silica NPs also could not only limit themore degradation enhanced of photothermal ICG, but reach effect and thanstay pureat a tumor ICG [168]. for a long period of time due to an enhanced permeability and glycol-albumin-curcuminbreast cancer cell line MD-MB-231. nanoparticles Entrapment exhibited efficiency an for prepared nanoparticle was above 95%. The polyethylene by slower and controlled release. Solubility of the drug effectiveretention way (EPR) to promote effect [169]. the application Hence, loading of ICG of in ICG PTT within and frominteresting the formulation release profile was increased.with small A initial sustained burst release followed of targeting nanocarriers with high efficiency is shown to be an in vitro and in vivo studies with the optimized formulation. PDTConclusion treatment. drugPolyethylene from nanoparticles glycol-albumin-curcumin was observed for 35nanoparticles days in both Multifunctional biodegradable and biocompatible showed lesser liver and kupffer cell uptake as compared polymeric nanoparticles loaded with indocyanine green to that of curcumin-albumin nanoparticles suggesting the (ICG) as an optical-imaging contrast agent for cancer imaging bestowment of stealthness to nanoparticles with pegylation. and as a photothermal therapy agent for cancer treatment. Also, the antiproliferative activity of polyethylene glycol- albumin-curcumin nanoparticle formulation was more (NPs) encapsulating superparamagnetic iron oxide (Fe O4), as compared to native curcumin. Polyethylene glycol- To improve the efficacy of PTT, polymeric nanoparticles 3 albumin-curcumin nanoparticles thus developed can be synergistic agents for NIR laser-induced PTT. indocyanine green (ICG), and perfluoropentane (PFP) as compared to conventional therapies and as an alternate to References nanoparticleconveniently albuminused in breast bound cancer technology with improvedwhich is usedefficacy in 1. producing Abraxane, albumin based breast cancer targeting Cheng L, Wang C, Feng LZ, Yang K, Liu Z (2014) Functional nanomaterials nanoparticles of paclitaxel [147]. Photothermal therapy 2. for phototherapies of cancer. Chem Rev 114: 10869-10939. Dolmans DE, Fukumura D, Jain RK (2003) Photodynamic therapy for physical tumor treatments utilizing near infrared (NIR) cancer. Nat Rev Cancer 3: 380-387. light-absorbing(PTT) and photodynamic agents which therapy lead to (PDT) thermal are ablation emerging of 3. Circu ML, AW TY (2010) Reactive oxygen species, cellular redox systems, cancer cells or generate highly reactive oxygen species (ROS) 4. and apoptosis. Free Radic Biol Med 48: 749-762. Schaafsma BE, Mieog JS, Hutteman M, van der Vorst JR, Kuppen PJ, et possess several advantages, such as minimal invasion, high al. (2011) The clinical use of indocyanine green as a near-infrared via photosensitizer to ablate tumors [148,149]. PTT and PDT fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol 104: 323-332. ISSN: 2581-7388 72 www.innovationinfo.org 491.

5. Mastropasqua R, Di Antonio L, Di Staso S, Agnifili L, Di Gregorio A, et al. 27. (2015) Optical Coherence Tomography Angiography in Retinal Vascular Zheng XH, Xing D, Zhou FF, Wu BY, Chen, et al. (2011) Indocyanine Diseases and Choroidal Neovascularization. J Ophthalmol 2015: 343- Targeting Probes for Optical Imaging and Photothermal Therapy. Mol Green- Containing Nanostructure as Near Infrared Dual-Functional 515. Indocyanine Green Usage in Surgery and Oncology: An Update. Ann Surg 6. Zelken JA, Tufaro AP (2015) Current Trends and Emerging Future of Pharmaceutics 8: 447-456. Tumor Treatment Using Biofunctional Indocyanine Green-Containing 28. Zheng XH, Zhou FF, Wu BY, Chen WR, Xing D (2012) Enhanced 7. Oncol Suppl 3 :1271-1283. Nanostructure by Intratumoral or Intravenous Injection. Mol formulated indocyanine green for near-infrared triggered photodynamic therapy:Shemesh in CS, vivo Moshkelani evaluation D, for Zhang triple-negative H (2015) Thermosensitive breast cancer. Pharm liposome Res 29. Pharmaceutics 9: 514-522. Romila M, Tingjun L, Yuan T, Alicia, Anthony J (2010) Cellular Uptake and 32: 1604-1614. Cytotoxicity of a Novel ICG-DOX-PLGA Dual Agent Polymer Nanoparticle 8. medulloblastomaBernardi RJ, Lowery and glioma: AR, Thompsonan in vitro evaluation PA, Blaney using SM, human West cell JL Delivery System SBEC 2010. IFMBE Proceedings 32: 228-231. (2008) Immunonanoshells for targeted photothermal ablation in Step Sustained-Release PLGA/Hyaluronic Acid Gel Formulation for 30. Intra-articularTakehiro N, Tomoyuki Administration. O, Ryota Biol M, TetsuyaPharm Bull O, Hirokazu O (2018) Two- 9. lines. J Neurooncol 86: 165-172. formulation of indocyanine green for phototherapy of melanoma. J 41: 937-943. Mundra V, Peng Y, Rana S, Natarajan A, Mahato RI (2015) Micellar Multifunctionality of indocyanine green-loaded biodegradable 31. nanoparticlesRonak H, Aniket for S,enhanced Nimit L, optical Venkaiah imaging C, Kytai and T, ethyperthermia al. (2012) Control Release 220: 130-140. 10. Saxena V, Sadoqi M, Shao J (2003) Degradation kinetics of indocyanine intervention of cancer. Journal of Biomedical Optics 17: 046003. 11. green in aqueous solution. J Pharm Sci 92: 2090-2097. Improve ICG Based Photodynamic Properties Through Conjugation of 32. ICG Tayebeh Into Nano-Graphene A, Maryam P, Oxide Nasim Against C, Sima Enterococcus S, Farzaneh faecalis H, et ”, al. Avicenna (2018) Mordon S, Devoisselle JM, Soulie-Begu S, Desmettre T (1998) Indocyanine green: physicochemical factors affecting its fluorescence in 12. vivo. Microvasc Res 55:146-152. J Clin Microb Infec 5: e64624. and metabolic features of indocyanine green (ICG) as related to Desmettre T, Devoisselle JM, Mordon S (2000) Fluorescence properties 33. multifunctionalBin Zheng, Yang anti-tumor Bai, Hongbin therapy Chen, via Huizhuo macrophages. Pan, Wanying Electronic Ji, et Supplementaryal. ((2018) Targeted Material delivery (ESI) for ofBiomaterials tungsten oxideScience,. nanoparticles for angiography. Surv Ophthalmol 45: 15-27. 13. Jain KK (2008) Nanomedicine: application of nanobiotechnology in 14. medical practice. Med Princ Pract 17: 89-101. 34. Samit Guha, Scott, Graeme T, Felicia M, Bradley D (2015) Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Doped Nanoparticles without Oxygen Photosensitization. Langmuir 31: Prog Polym Sci 32: 762-798. 7826-7834. O loaded PLGA 15. Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as 4 35. Chengchengnanoparticles Niu,for photothermal Yan Xu, Senbo An, Ming Zhang, Yihe Hu, et al. biodegradable controlled drug delivery carrier. Polymers 3: 1377-1397. (2017) Near-infrared induced phaseshifted ICG/Fe3 16. Fishburn CS (2008) The pharmacology of PEGylation: Balancing PD with tumor ablation. Scientific Reports 7: 17. PK to generate novel therapeutics. J Pharm Sci 97:4167-4183. 5490. Physiochemical studies on indocyanine green: molar lineic absorbance, green encapsulated biocompatible poly (lactic-co-glycolic) acid pH BjoÈrnssontolerance, activation OG, Murphy energy R, and Chadwick rate of decay VS, BjoÈrnsson in various solvents. S (1983) J 36. nanoparticles Hrebesh, Hui withXie, Jeffrey, photothermal Owen (2012) optical Optical coherence detection tomography. of indocyanine Optics

Clin Chem Clin Biochem 21: 453-458. Letters 37. stability and aqueous-stability of indocyanine green in polymeric 19 In 18. Saxena V, Sadoqi M, Shao J (2004) Enhanced photo-stability, thermal- 37. vivoEdyta Photoacoustic, Swider, KhalidF Daoudi,Magnetic Alexander, Resonance Olga And Koshkina Fluorescent et al. Imaging. (2018) NanotheranosticsClinically- Applicable Perfluorocarbon-Loaded Nanoparticles For 19. nanoparticulate systems. J Photochem Photobiol B 74: 29-38. indocyanine green within dextran-coated mesocapsules by absorbance 2: 258-268. Yaseen MA, Yu J, Wong MS, Anvari Bn (2007) Stability assessment of 38. Dolmans, Fukumura, Jain (2003) Photodynamic therapy for cancer. Nat spectroscopy. J Biomed Opt 12: 064031. Rev Cancer 3: 380-387. green-loaded biodegradable tumor targeting nanoprobes for in vitro and cancer review of current status and future promise. Nat Clin Pract Urol 20. Zhengin vivo CF, Zheng MB, Gong P, Jia AG, Zhang PF, et al. (2012) Indocyanine 39. Moore, Pendse, Emberton (2009) Photodynamic therapy for prostate

21. imaging. Biomaterials 33: 5603-5609 6: 18-30.

forAltinoglu In Vivo EI, Russin TJ, Kaiser JM, Barth BM, Eklund PC, et al. (2008) Near- 40. Lucky, Soo, Zhang (2015) Nanoparticles in photodynamic therapy. Chem Infrared Emitting Fluorophore-Doped Calcium Phosphate Nanoparticles 41. Rev 115: 1990-2042. 22. Imaging of Human Breast Cancer. ACS Nano 2: 2075-2084. Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and Liu H, Farrell S, Uhrich K (2000) Drug release characteristics of 42. anti-tumour immunity. Nat Rev Cancer 6: 535-545. unimolecular polymeric micelles. J Controlled Release 68: 167-174. dot photodynamic therapy agent with high singlet oxygen generation. Ge JC, Lan MH, Zhou BJ, Liu WM, Guo L, et al. (2014) A graphene quantum 23. Lavasanifar A, Samuel J, Kwon GS (2002) Poly (ethylene oxide)-block- poly (L-amino acid) micelles for drug delivery. Adv Drug Delivery Rev Nat Commun 5: 4596. 24. 54: 169-190. Reversible Response to Thermal/pH Modulation for Optical Imaging. 43. Macdonald IJ, Dougherty TJ (2001) Basic principles of photodynamic Chen YP, Li XD (2011) Near-Infrared Fluorescent Nanocapsules with 44. therapy. J. Porphyrins Phthalocyanines 5: 105-129. interaction with skin A photothermal effect analysis. Opt. Laser Technol Guan KW, Jiang YQ, Sun CS, Yu H (2011) A two-layer model of laser Biomacromolecules 12: 4367-4372. of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles 25. Kim TH, Chen Y, Mount CW, Gombotz WR, Li XD, et al. (2010) Evaluation 43: 425−429. 45. Brown S (2008) Photodynamic Therapy-Two photons are better than for Noninvasive Near- Infrared Tumor Imaging. Pharm Res 27: 1900- one.Mitsunaga Nat Photonics M, Ogawa 2: 394-395. M, Kosaka N, Rosenblum LT, Choyke PL, et al. 1913. 46. 26. Kirchherr AK, Briel A, Mader K (2009) Stabilization of indocyanine green (2011) Cancer cell-selective in vivo near infrared photoimmunotherapy by encapsulation within micellar systems. Mol Pharmaceutics 6: 480- targeting specific membrane molecules. Nat Med 17: 1685-1691. ISSN: 2581-7388 73 www.innovationinfo.org 47.

Chen GY, Qiu HL, Prasad PN, Chen XY (2014) Upconversion Nanoparticles: Chemistry, solubility and fiber formation. Prog Polym Sci 34: 641-78. Design, Nanochemistry, and Applications in Theranostics. Chem Rev characterization of amphotericin B- chitosan-dextran sulfate 69. Tiyaboonchai W, Limpeanchob N (2007) Formulation and 114:: 5161-5214. of Functional Upconversion Nanoparticles for Targeted Cancer Imaging 48. Liang LE, Care A, Zhang R, Lu YQ, Packer NH, et al. (2016) Facile Assembly nanoparticles. Int J Pharm 329: 142-149. 70. Sonaje K, Chen YJ, Chen HL, Wey SP, Juang JH, et al. (2010) Enteric- 49. and Photodynamic Therapy. ACS Appl Mater Interfaces 8: 11945-11953. Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin coated capsules filled with freeze-dried chitosan/poly(γ-glutamic acid) Kamkaew A, Cheng L, Goel S, Valdovinos HF, Barnhart TE, et al. (2016) 71. nanoparticles for oral insulin delivery. Biomaterials 31: 3384-3394. drug delivery: Chitosan coating improves stability, controlled delivery, Luo Y, Teng Z, Li Y, Wang Q (2015) Solid lipid nanoparticles for oral e6-Loaded Hollow Mesoporous Silica Nanoparticles. ACS Appl. Mater. mucoadhesion and cellular uptake. Carbohydr Polym 122: 221-229. Interfaces 8: 26630-26637. 72. 50. Tang YG, Hu J, Elmenoufy AH, Yang XL (2015) Highly Efficient FRET Duttagupta DS, Jadhav VM, Kadam VJ (2015) Chitosan: A propitious System Capable of Deep Photodynamic Therapy Established on X-ray biopolymer for drug delivery. Curr Drug Deliv 12: 369-381. Excited Mesoporous LaF3:Tb Scintillating Nanoparticles. ACS Appl. nanoparticles: Effect of cross-linking with tripolyphosphate and charge Mater. Interfaces 7: 12261-12269. 73. Rodrigues S, Costa AMR Da, Grenha (2012) A Chitosan/carrageenan radiation and photodynamic therapies for cancer treatment. J. Nanosci. 51. Chen W, Zhang J (2006) Using nanoparticles to enable simultaneous 74. ratios. Carbohydr Polym 89: 282-289. nanoparticles for delivery of an anti-angiogenesis peptide. Lett Pept Sci Nanotechnol 6: 1159-1166. Chen Y, Mohanraj VJ, Parkin JE (2003) Chitosan-dextran sulfate 52. Hu J, Tang YA, Elmenoufy AH, Xu HB, Cheng Z, et al. (2015) 10: 621-629. Nanocomposite- Based Photodynamic Therapy Strategies for Deep Tumor Treatment. Small 11: 5860-5887. 75. Rinaudo M, Pavlov G, Desbrières J (1999) Influence of acetic acid deep photodynamic therapy modality combined with CT imaging concentration on the solubilization of chitosan. Polymer (Guildf) 40: 53. Elmenoufy AH, Tang YA, Hu J, Xu HB, Yang XL (2015) A novel 7029-32. Synthesis and characterization of pH-dependent glycol chitosan and established via X-ray stimulated silica-modified lanthanide scintillating 76. dextranSaboktakin sulfate MR, nanoparticlesTabatabaie RM, for Maharramov effective brain A, Ramazanovcancer treatment. MA (2011) Int J nanoparticles. Chem. Commun 51: 12247-12250. hydrogels for cell-based sensing and optogenetic synthesis in vivo. Nat. 54. Choi M, Choi J, Kim S, Nizamoglu S, Hahn SK, et al. (2013) Light-guiding 77. Biol Macromol 49: 747-751. degradation rates of partially N- acetylated chitosans in human serum. Photonics 7: 987-994. Vårum KM, Myhr MM, Hjerde RJN, Smidsrød O (1997) In vitro 55. Kim TI, McCall JG, Jung YH, Huang X, Siuda, et al. (2013) Cellular-Scale Carbohydr Res 299: 99-101. Optoelectronics with Applications for Wireless Optogenetics. Science properties of chitosan microspheres prepared by different methods. 340: 211-216. 78. Dhawan S, Singla AK, Sinha VR (2004) Evaluation of mucoadhesive Heating of Intraperitoneal Tumors through the Use of an Implanted 56. Bagley AF, Hill S, Rogers GS, Bhatia SN (2013) Plasmonic Photothermal 79. AAPS PharmSciTech 5. Near-Infrared Source. ACS Nano 7: 8089-8097. Janes KA, Fresneau MP, Marazuela A, Fabra A, Alonso MJ (2001) Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release 73: 57. Widder EA (2010) Bioluminescence in the ocean: origins of biological, 255-267. chemical, and ecological diversity. Science 328: 704-708. 80. Xiao B, Laroui H, Viennois E, Ayyadurai S, Charania MA, et al (2014) 58. Herring PJ (1977) Bioluminescence of marine organisms. Nature 267: Nanoparticles with surface antibody against CD98 and carrying CD98 788-793. small interfering RNA reduce colitis in mice. Gastroenterology 146: 59. Li J, Chen L, Du L, Li M (2013) Cage the firefly luciferin!−a strategy for 1289-300. developing bioluminescent probes. Chem Soc Rev 42: 662-676. spectrometer determining quantum yields: Reexamination of the 81. Tekie FSM, Atyabi F, Soleimani M, Arefian E, Atashi A, et al. (2015) 60. aqueousAndo Y (2007)luminol Development chemiluminescence of a quantitative standard. bio/chemiluminescence Photochem Photobiol Chitosan polyplex nanoparticle vector for miR-145 expression in MCF-7: Optimization by design of experiment. Int J Biol Macromol 81: 828-837. substantiation of health claims related to chitosan. EFSA J 9: 1-21. 82. European Food Safety Authority (2011) Scientific opinion on the 83: 1205-1210. 61. El-Dakdouki MH, Xia JG, Zhu DC, Kavunja H, Grieshaber J, et al. (2014) 83. Shields KM, Smock N, McQueen CE, Bryant PJ (2003) Chitosan for weight Assessing the in Vivo Efficacy of Doxorubicin Loaded Hyaluronan loss and cholesterol management. Am J Heal Pharm 60:1310-1313. Nanoparticles. ACS Appl Mater Interfaces 6: 697-705. in lipid-lowering treatment: A narrative review on the role of chitosan. induced light-activated system for anticancer and antifungal activities. J 84. Patti AM, Katsiki N, Nikolic D, Al-Rasadi K, Rizzo M (2015) Nutraceuticals 62. Yuan H, Chong H, Wang B, Zhu C, Liu L, et al. (2012) Chemical molecule- Angiology 66: 416-421. Am Chem Soc 134: 13184-13187. effect. AnnPharmacother 41: 1912-1914. infrared dots for in vivo lymph-node mapping and tumour imaging. Nat. 85. Huang SS, Sung SH, Chiang CE (2007) Chitosan potentiation of warfarin 63. Xiong L, Shuhendler AJ, Rao J (2012) Self-luminescing BRETFRET near- serum valproate and increase the risk of seizure reappearance. BMJ. Commun 3: 1193. 86. Striano P, Zara F, Minetti C, Striano S (2009) Chitosan may decrease resonance energy transfer using luciferase-immobilized quantum dots 64. Hsu CY, Chen CW, Yu HP, Lin YF, Lai PS (2013) Bioluminescence prepared by complexation with polysaccharides: Carrageenan versus 87. Cheow WS, Kiew TY, Hadinoto K (2015) Amorphous nanodrugs for self-illuminated photodynamic therapy. Biomaterials 34: 1204-1212. dextran sulfate. Carbohydr Polym 117:549-558. 65. Kim YR, Kim S, Choi JW, Choi SY, Lee SH, et al. (2015) Bioluminescence- Activated Deep-Tissue Photodynamic Therapy of Cancer. Theranostics 88. Hiebert LM, Wice SM, Jaques LB, Williams KE, John M (1999) Orally 5: 805-817. administered dextran sulfate is absorbed in HIV-positive individuals. J Lab Clin Med 161-170. 66. Cui Z, Nair LS (2010) Chitosan: A Versatile Biomedical Polymer. Recent Pat Biomed Eng 3: 129-137. 89. 974.McCarthy RE, Arnold LW, Babcock GF (1977) Dextran sulphate: an of micro/nanoparticles based on natural polysaccharides. Carbohydr adjuvant for cell-mediated immune responses. Immunology 32: 963- 67. Yang J, Han S, Zheng H, Dong H, Liu J (2015) Preparation and application containing polyethylenimine-dextran sulfate nanoparticles. Int J Pharm Polym 123: 53-66. 90. Tiyaboonchai W, Woiszwillo J, Sims RC, Middaugh CR (2003) Insulin 68. Pillai CKS, Paul W, Sharma CP (2009) Chitin and chitosan polymers: 255: 139-151. ISSN: 2581-7388 74 www.innovationinfo.org 91.

Smith KM, Chang RS, Tabba HD, Yongsheng He (1988) Dextran sulfate as Reduced cardiotoxicity and comparable efficacy in a Phase III trial an inhibitor against the human immunodeficiency virus (42811). Proc of pegylated liposomal doxorubicin HCl (CAELYX/doxil) versus 92. Soc Exp Biol Med 189: 304-309. conventional doxorubicin for first-line treatment of metastatic breast Mechanism of inhibitory effect of dextran sulfate and heparin on 111. cancer. Ann Oncol 15: 440-449. Baba M, Pauwels R, Balzarini J, Arnout J, Desmyter J, et al. (1988) Evidence of RNAi in humans from systemically administered siRNA Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, et al. (2010) replication of human immunodeficiency virus in vitro. Proc Natl Acad Sci USA 85:6132-6136. 112. via targeted nanoparticles. Nature 464: 1067-1070. Recognition of dextran-superparamagnetic iron oxide nanoparticle a dopamine agonist for the treatment of Type 2 diabetes. Expert Opin. 93. conjugatesChao Y, Makale (feridex) M, Karmali via macrophage PP, Sharikov scavenger Y, Tsigelny receptor I, et al. charged (2012) Scranton R, Cincotta A (2010) Bromocriptine - unique formulation of

Pharmacother. 11: 269-279. 94. domains.Persson UC, Bioconjug Hammarström Chem 23:1003-1009. LTG, Smith CIE. (1977) Macrophages are pharmacokinetic study of a weekly liposomal paclitaxel formulation required for the dextran sulfate induced activation of B lymphocytes. J 113. Lim WT, Tan EH, Toh CK, Hee SW, Leong SS, et al. (2009) Phase I

114. (Genexol-PM) in patients with solid tumors. Ann Oncol 21: 382-388. Immunol.;119:1138-1144. associated platelet aggregation by heparin and dextran sulfate, and its Winter PM, Morawski AM, Caruthers SD et al. (2003) Molecular 95. Suzuki K, Nishioka J, Hashimoto S (1979) Inhibition of factor VIII- imaging of angiogenesis in early-stage atherosclerosis with avb3- integrin-targeted nanoparticles. Circulation 108: 2270-2274. mechanism. Biochim Biophys Acta 585: 416-426. imaging of small living subjects using Raman spectroscopy. Proc Natl of G-CSF in dextran sulfate sodium-induced acute colitis through 115. Keren S, Zavaleta C, Cheng Z et al. (2008) Noninvasive molecular 96. Meshkibaf S, Martins AJ, Henry GT, Kim SO (2016) Protective role Acad Sci 105: 5844-5849. 97. generating gut-homing macrophages. Cytokine 78: 69-78. nanoscale: optical and photothermal properties and some applications 116. Jain PK, Huang X, El-Sayed IH, El-Sayed MA (2008) Noble metals on the Munyaka PM, Rabbi MF, Khafipour E, Ghia JE (2016) Acute dextran sulfate sodium (DSS)- induced colitis promotes gut microbial dysbiosis in imaging, sensing, biology, and medicine. Acc Chem Res 41: 1578- in mice. J Basic Microbiol 1-13. 117. 1586. sulfate for the prevention of graft rejection during pancreatic islet permeability and the EPR effect in macromolecular therapeutics: a 98. transplantation.European Medicines Agency. (2011) Low molecular weight dextran Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular

99. European Medicines Agency. Low molecular weight dextran sulfate review. J Control Release 65: 271-284. as treatment for mobilisation of progenitor cells prior to stem cell glycol) in drug delivery: pros and cons as well as potential alternatives. transplantation. 118. Knop K, Hoogenboom R, Fischer D, Schubert US (2006) Poly(ethylene

119. Angew Chem Int Ed Engl 49: 6288-6308. 100. polymericAntony V. nanoparticles Samrot, Ujjala from Burman, crab Sherylshell derived Ann Philip, chitosan Shobana for drug Na, van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)- Kumar Chandrasekaran (2018) Synthesis of curcumin loaded modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res 24: 1405-1414. delivery. Informatics in Medicine Unlocked 10: 159-182. Thioalkylated tetraethylene glycol: a new ligand for water soluble Synthesis of Chitosan/Gelatin granule containing amine derivated 120. Kanaras AG, Kamounah FS, Schaumburg K, Kiely CJ, Brust M (2002) 101. octa(ammoniumHamideh Moshkbar, chloride) Nasser Arsalani,substituted Laleh Polyhedral Saleh Ghadimi Oligomeric (2018) 121. Silsesquioxane and investigating its application as a drug carrier. monolayer protected gold clusters. Chem Commun 20: 2294-2295. International Journal of Polymeric Materials and Polymeric Kwon GS (2003) Polymeric micelles for delivery of poorly water- 122. soluble compounds. Crit Rev Ther Drug Carrier Syst. 20: 357-403. Biomaterials 1-8. Gref R, Minamitake Y, Peracchia MT, et al. (1994) Biodegradable long- circulating polymeric nanospheres. Science 263: 1600-1603. 102. SystemHaliza Katas,for Protein/siRNA. Maria Abdul International Ghafoor Raja, Journal Kai of Leong Biomaterials Lam (2013) 9. Development of Chitosan Nanoparticles as a Stable Drug Delivery 123. Roberts MJ, Bentley MD, Harris JM (2002) Chemistry for peptide and 124. protein PEGylation. Adv Drug Deliv Rev 54: 459-476. Preparation and Characterization of Mucoadhesive Buccal 103. Ji Woon Suh, Ji-Soo Lee, Sanghoon Ko, Hyeon Gyu Lee (2016) Li D, He Q, Li J (2009) Smart core/shell nanocomposites: intelligent polymers modified gold nanoparticles. Adv Colloid Interface Sci 149: Nanoparticles Using Chitosan and Dextran Sulfate. J Agric Food Chem 28-38. 64: 5384-5388. polymer for functionalization of nanomaterials with ultralong blood sulfate nanoparticles for delivery of an anti-angiogenesis Peptide. 125. Prencipe G, Tabakman SM, Welsher K, et al. (2009) PEG branched 104. Yan Chen, Vellore J. Mohanraj, John E. Parkin (2003) Chitosan-dextran circulation. J. Am. Chem. Soc. 131: 4783-4787. Letters in Peptide Science 10: 621-629. of Indocyanine Green to Cancer Cells by Chitosan-Based Nanocarriers. 126. Saba TM (1970) Physiology and physiopathology of the 105. Fwu-Long Mi, Yu-Ru Su, Shu-Huei Yu, An-Chong Chao (2003) Delivery 127. reticuloendothelial system. Arch Intern Med 126: 1031-1052. polycyanoacrylate nanoparticles for intravenous administration and Peracchia MT, Fattal E, Desmaële D, et al. (1999) Stealth PEGylated J Pharm Sci 92: 2090-2097. Synthesis and Characterization of Chitosan-Coated Near-Infrared 106. Pei-Ru Wei, Yaswanth Kuthati, Ranjith Kumar K, Chia-Hung Lee (2015) splenic targeting. J Control Release 60: 121-128. for Potential Applications in Photodynamic Therapy. International 128. Owens D 3rd, Peppas N (2006) Opsonization, biodistribution, and (NIR) Layered Double Hydroxide- Indocyanine Green Nanocomposites pharmacokinetics of polymeric nanoparticles. Int. J. Pharmaceut. 307: 129. 93-102. Journal of Molecular Sciences, Int J Mol Sci 16: 20943-20968. Decker K (1990) Biologically active products of stimulated liver 107. Wagner V, Dullaart A, Bock A, Zweck A (2006) The emerging macrophages (Kupffer cells). Eur J Biochem 192: 245-261. nanomedicine landscape. Nat. Biotechnol. 24: 1211-1218. 130. Zolnik BS, Sadrieh N (2009) Regulatory perspective on the importance 108. Kim BY, Rutka JT, Chan WC (2010) Nanomedicine. N Eng J Med 363: of ADME assessment of nanoscale material containing drugs. Adv Drug 2434-2443. Deliv Rev 61: 422-427. 109. Jacobson GB, Gonzalez-Gonzalez E, Spitler R, Shinde R, Leake D, et on aggregation and transport of titania nanoparticles. Environ Sci 131. Guzman K, Finnegan M, Banfield J (2006) Influence of surface potential al. (2010) Biodegradable nanoparticles with sustained release of functional siRNA in skin. J Pharm Sci 99: 4261-4266. Technol 40: 7688-7693. 110. O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, et al. (2004) 132. Yang P, Ando M, Murase N (2010) Various Au nanoparticle ISSN: 2581-7388 75 www.innovationinfo.org organizations fabricated through SiO2 monomer induced self- ultrasound imaging guided tumor photodynamic therapy. Biomaterials

assembly. Langmuir 27: 895-901. 112: 324-335. of a high energy facet as a means of controlling the shapes of TiO2 activated photodynamic therapy mediated by indocyanine green with 133. Jun Y, Casula M, Sim J, et al. (2003) Surfactant-assisted elimination 153. Luo T, Zhang Q, Lu QB (2017) Combination of near infrared light-

nanocrystals. J Am Chem Soc 125: 15981-15985. etoposide to treat non-small-cell lung cancer. Cancers 9: 63. based intrinsic theranostic nanomedicines with high photothermal 134. Forster S, Antonietti M (1998) Amphiphilic block copolymers in 154. Zhang S, Guo W, Wei J, Li C, Liang XJ, Yin M (2017) Terrylenediimide- structure-controlled nanomaterial hybrids. Adv Mat 10: 195-217. conversion efficiency for photoacoustic imaging-guided cancer 135. Zhao W, Brook M, Li Y (2008) Design of gold nanoparticle based therapy. ACS Nano 11: 3797-3805. colorimetric biosensing assays. Chem Bio Chem 9: 2363-2371. nanoparticles as a versatile molecular loading platform to enable using the Smoluchowski equation and the slope of the current–time 155. Dong Z, Gong H, Gao M, Zhu W, Sun X, et al. (2016) Polydopamine 136. Sze A, Erickson D, Ren L, Li D (2003) Zeta-potential measurement imaging-guided cancer combination therapy. Theranostics 6: 1031- relationship in electroosmotic flow. J Colloid Interface Sci 261: 402- 1042. 410. the clearance and biodistribution of polymeric nanoparticles. Mol 156. Song S, He S, Tao Y, Wang L, Han F, et al. (2017) Indocyanine green 137. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting magnetic resonance dual-modal imaging and photothermal therapy of loaded magnetic carbon nanoparticles for near infrared fluorescence/ Pharm 5: 505-515. tumor. ACS Appl. Mater. Interfaces 9: 9484-9495. 138. Strickley RG (2004) Solubilizing excipients in oral and injectable 157. Li X, Xing L, Hu Y, Xiong Z, Wang R, et al. (2017) An RGD- modified formulations. Pharm Res 21: 201-230. hollow silica@Au core/shell nanoplatform for tumor combination 139. minimizeTan JS, Butterfield interactions DE, Voycheckwith blood CL, Caldwellcomponents KD, Liand JT (1993)prolong Surface blood therapy. Acta Biomater. 62: 273-283. modification of nanoparticles by PEO/PPO block copolymers to photothermal and photodynamic inactivation of cancer cells through 158. surfaceChu CK, plasmonTu YC, Hsiao resonance JH, Yu ofJH, a Yugold CK, nanoring. et al. (2016) Nanotechnology Combination 27: of circulation in rats. Biomaterials 14: 823-833. 140. Mueller BG, Kissel T (1993) Camouflage nanospheres: a new approach 115102. to bypassing phagocytic blood clearance by surface modified 159. Jia Q, Ge J, Liu W, Liu S, Niu G, et al. (2016) Gold nanorod@silica- 141. particulate carriers. Pharmaceut Pharmacol Lett 3: 67-70. and photoacoustic imaging-guided synergistic photodynamic/ polyethyleneglycols effectively prolong the circulation time of carbon dots as multifunctional phototheranostics for fluorescence Klibanov AL, Maruyama K, Torchilin VP, Huang L (1990) Amphipathic photothermal therapy. Nanoscale 8: 13067-13077. 142. liposomes. FEBS Lett 268: 235-237. 160. Peng S, He Y, Er M, Sheng Y, Gu Y, et al. (2017) Biocompatible CuS-based Kataoka K, Harada A, Nagasaki Y (2001) Block copolymer micelles for nanoplatforms for efficient photothermal therapy and chemotherapy drug delivery: design, characterization and biological significance. Adv in vivo. Biomater Sci 5: 475-484. Drug Deliv Rev 47: 113-131. polymer composites containing cyanines for near-infrared of covalent attachment of polyethylene-glycol on immunogenicity and 161. Wang W, Wang L, Liu S, Xie Z (2017) Metal-organic frameworks@ 143. Abuchowski A, McCoy JR, Palczuk NC, Vanes T, Davis FF (1977) Effect fluorescence imaging and photothermal tumor therapy. Bioconjugate 144. circulating life of bovine liver catalase. J Biol Chem 252: 3582-3586. Chem 28 2784-2793. immunological properties of bovine serum-albumin by covalent Carbon nanotubes introduced into the abdominal cavity of mice show Abuchowski A, Vanes T, Palczuk NC, Davis FF (1977) Alteration of 162. Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, et al. (2008)

attachment of polyethylene-glycol. J Biol Chem 252: 3578-3581. asbestos-like pathogenicity in a pilot study. Nat Nanotechnol 3: 423- Blood elimination kinetics and organ distribution of microparticles 428. 145. Arturson P, Laakso T, Edman P (1983) Acrylic microspheres in vivo. 163. Liu H, Liu T, Wu X, Li L, Tan L, et al. (2012) Targeting gold nanoshells with different surface characteristics. J Pharm Sci 72: 1415-1420. on silica nanorattles: A drug cocktail to fight breast tumors via a single irradiation with near- infrared laser light. Adv Mater 24: 755-761. 146. Petros RA, DeSimone JM (1999) Strategies in the design of nanostar- coated hollow mesoporous silica for tumor multimodality nanoparticles for therapeutic applications. Nat Rev Drug Discov 9: 164. imagingLi X, Xing and L, Zhengphotothermal K, Wei P,therapy. Du L, et ACS al. (2017)Appl Mater Formation Interfaces of gold 9: 147. 615-627. of doxorubicin levels in whole tumor and tumor nuclei in murine Laginha KM, Verwoert S, Charrois GJ, Allen TM (2005) Determination 5817-5827. Supramolecular stacking of doxorubicin on carbon nanotubes for in breast cancer tumors. Clin Cancer Res 11: 6944-6949. 165. Liu Z, Fan AC, Rakhra K, Sherlock S, Goodwin A, et al. (2009) radiofrequency ablation and adjuvant liposomal chemotherapy: effect 148. Ahmed M, Lukyanov AN, Torchilin V, et al. (2005) Combined of chemotherapeutic agent, nanoparticle size, and circulation time. J vivo cancer therapy. Angew Chem Int Ed 48: 7668-7672. Indocyanine green-encapsulated hybrid polymeric nanomicelles for 166. Jian WH, Yu TW, Chen CJ, HuangWC, Chiu HC, Chiang WH (2015) 149. Vasc Interv Radiol 16: 1365-1371. photothermal cancer therapy. Langmuir 31: 6202-6210. Gabizon A, Shmeeda H, Barenholz Y (2003) Pharmacokinetics of PEGylated liposomal Doxorubicin: review of animal and human 167. Wu M, Wang Q, Zhang D, Liao N, Wu L, et al. (2016) Magnetite studies. Clin Pharmacokinet 42: 419-436. nanocluster@poly(dopamine)- PEG@ indocyanine green nanobead with magnetic field-targeting enhanced MR imaging and photothermal 150. Moreno-Aspitia A, Perez EA (2005) Nanoparticle albumin-bound therapy in vivo. Colloids Surf B 141: 467-475. paclitaxel (ABI-007): a newer taxane alternative in breast cancer. layered supramolecular nanovehicle for combined dual-modal FutureThadakapally Oncol. 1:R, 755-762. Aafreen A, Aukunuru J, Habibuddin M, Jogala S 168. Guan S, Weng Y, Li M, Liang R, Sun C, et al. (2017) An NIR-sensitive 151. imaging and synergistic therapy. Nanoscale 9: 10367-10374. (2016) Preparation and Characterization ofPEG-albumin-curcumin drug release from calcium carbonate-encapsulated gold nanostars for Nanoparticles Intended to Treat Breast Cancer. Indian J Pharm Sci 78: 169. near-infraredLiu Y, Zhi X, Yangphotodynamic/photothermal M, Zhang J, Lin L, et al. (2017)combination Tumor-triggered antitumor 65‑72. 152. Gao S, Wang G, Qin Z, Wang X, Zhao G, et al. (2017) Oxygen-generating therapy. Theranostics 7: 1650-1662. hybrid nanoparticles to enhance fluorescent/photoacoustic/ Citation: Saboktakin M (2019) Polymeric Nanoencapsu-lation of Indocyanine Green for Photodynamic Therapy Technique. J Biomed Res Rev Vol: 2, Issu: 1 (62- 76).

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