Chemical Society Reviews Near Infrared light responsive nanomaterials in cancer therapeutics Journal: Chemical Society Reviews Manuscript ID: CS-REV-01-2014-000011.R1 Article Type: Review Article Date Submitted by the Author: 07-Mar-2014 Complete List of Authors: Shanmugam, Vijayakumar; National Cheng Kung University, Department of Chemistry Selvakumar, Subramanian; National Cheng Kung University, Department of Chemistry Yeh, Chen-Sheng; National Cheng Kung University, Department of Chemistry Page 1 of 36 Chemical Society Reviews Journal Name ARTICLE Near-infrared light-responsive nanomaterials in cancer therapeutics Vijayakumar Shanmugam ‡ S. Selvakumar ‡ and Chen-Sheng Yeh* Noninvasive techniques, such as breath tests (urea breath test), blood pressure measurements using a sphygmomanometer, and electrocardiography, were employed by a physician to perform classical diagnosis. The use of state-of-the-art noninvasive therapies at the organ level in modern medicine has gradually become possible. However, cancer treatment demands for spatially and temporally controlled noninvasive therapy at the cell level because nonspecific toxicity often causes complicated side effects. To increase survival in cancer patients further, combination therapy and combination drugs are explored which demand for high specificity to avoid combined drug side effects. We believe that high specificity could be obtained by implementing near-infrared (NIR) light-assisted nanoparticles in photothermal therapy, chemotherapy-, and photodynamic therapy. To refine this therapy and subsequently achieve high efficiency, novel nanomaterials have been designed and modified either to enhance the uptake and drug delivery to the cancer site, or control treatment to administer therapy efficiently. These modifications and developments have been demonstrated to achieve special and temporal control when conducting an in vivo xenograft, because the NIR light effectively penetrated the biological tissue. The nanoplatforms discussed in this review are grouped under the following subheadings: Au nanorods (NRs), Au nanoshells, other Au-related nanomaterials, graphene oxide, upconversion nanoparticles, and other related materials (including materials such as CuS, Fe 3O4-related systems, and carbon nanotubes (CNTs)). A. Introduction the direct effect of these particles on heat delivery to the site, when illuminated using an NIR laser for PTT, these heat-transducing Cancer is a serious disease that challenges the survival of nanoparticles can also demonstrate controlled drug release through people in all age groups, especially those living in developed the transduction of heat to the thermoresponsive drug reservoirs, countries. Cancer is the uncontrolled growth of cells that can occur such as polymers and supramolecules, coated on heat-transducing in any type of tissue, and at the later stage begins to migrate and nanoparticles. Furthermore, these nanoparticles can transport the relocate to noncancerous tissue. This spread of cancer is called photodynamic agent, so that the NIR can be additively used for metastasis. Therefore, treating cancer at the early stage is optimal. photodynamic therapy (PDT). PDT involves using the reactive However, the only treatment option is to kill the cancer cells, which oxygen species (ROS) to kill the cancer cells, which is produced could result in detrimental consequences. If the cancer cells are not from the photodynamic agent. 2,3 The light is nontoxic when not killed, then the cancer spreads, but if the cancer cells are killed, combined with the photodynamic agent; similarly, the photodynamic healthy cells are likely to be damaged as well. Consequently, agent is nontoxic when not combined with the excitation energy of selectively killing the cancer cells without damaging healthy light. Thus, phototoxicity can be performed and controlled externally noncancerous cells is challenging, but can be accomplished by using using these nanoplatforms to avoid collateral damage, which is a nanotechnology. In classical terms, nanotechnology can be used to serious side effect of cancer chemotherapy. For example, the transport drugs to a specific site using specific markers. However, indocyanine green (ICG) photodynamic agent requires low these markers are not unique to the cancer cells; they are excitation energy and, thus, can be excited using an NIR laser. overexpressed, which also happens in pluripotent or young healthy Consequently, ICG can be loaded into a transducer, such as nanorod cells as well. Hence this marker-assisted deliver has a chance to get (NR), to implement the NIR laser in performing PTT using the NR misdirected. Therefore, using external stimulation to control the and PDT from ICG. This combination therapy enhances the release of drugs systemically is the goal in developing next- therapeutic effects of the treatment. However, not all photodynamic generation treatment. This can be accomplished by using optical agents exhibit a similar low excitation-energy requirement because nanoparticles exhibiting near-infrared (NIR) absorbance. As water most efficient ROS producers require the presence of high-energy and blood cells absorb NIR hardly, NIR can penetrate the tissue to photons in the visible wavelength, which cannot penetrate the tissue reach the deeply placed optically sensitive nanoparticles. The effectively. In this context, recently developed upconversion penetrating NIR radiation can be transduced into local heat by the nanoparticles (UCNPs) are a promising candidate for overcoming nanoparticles; consequently, this heat can be envisaged for the this limitation by providing high energy from the incident NIR photothermal therapy (PTT). Otherwise, potentially harsh traditional energy through upconversion. Thus, these UCNPs have given hyperthermia methods such as using a hot-water bath, heated blood clinical hope for PDT. perfusion, or an electromagnetic approach were used. 1 In addition to However, this NIR-assisted therapy may still be challenged in the clinical setting by the technique of stimulating the tumors located deep in the tissues. Numerous studies have Department of Chemistry and Department of Materials Science and emphasized the strategy of reaching deep-seated tumors using Engineering,National Cheng Kung University Tainan 701, Taiwan optical fibers. Recently, Batia et al . implanted an NIR source to E-mail: [email protected] irradiate deep-seated tumors for performing PTT using NRs as ‡ These authors contributed equally photothermal antenna. 4 Therefore, the use of this class of nanomaterials will change cancer therapy radically in the near future. In this review, we identified the potential NIR-absorbing This journal is © The Royal Society of Chemistry 2012 J. Name ., 2012, 00 , 1-3 | 1 Chemical Society Reviews Page 2 of 36 ARTICLE Journal Name nanomaterials used for PTT, drug delivery, and PDT, from the biocompatibility and conjugation of the targeting proteins or literatures and discussed the ability of these nanomaterials to treat peptides for enhancing uptake and increasing PTT efficiency; (2) the various cancers using modified nanoplatforms according to tumor mechanism of Au NRs-assisted PTT involving membrane targeting specificity to improve the efficiency of the treatment. The permeability, the influx of the cation, and actin damage; and (3) Au nanoplatforms discussed are grouped under the following NRs in conjugation with other functional nanoparticles were subheadings: Au NRs, Au nanoshells, other Au-related nanomaterials, designed to produce multifunctionalities. graphene oxide, UCNPs, and other related materials (including 10 materials such as CuS, Fe 3O4-related systems, and carbon nanotubes Huang et al. studied the applications of Au NRs in (CNT)). The aim of this review is to provide a summary of imaging and PTT. In this trial, Au NRs were synthesized using seed- nanoplatforms, their modifications, and their efficiency in producing mediated method with the assistance of CTAB. Au NRs coated with a photo-induced therapeutic effect. a CTAB bilayer were masked using poly(styrenesulfonate) (PSS) polymer through electrostatic attraction. To conduct in vitro imaging B. Au nanorod and therapy, both human oral squamous cell carcinomas (HOC 313 clone 8 and HSC 3) and the human keratinocyte nonmalignant oral B.1. Properties and synthesis epithelial cell line (HaCat) were used. Because the malignant cells overexpress the epidermal growth factor receptor (EGFR), the PSS- Au NR is an attractive nanostructure that demonstrates coated Au NRs were coated with targeting antiEGFR antibodies to unique optical behaviour. This optical behaviour is caused by the form antiEGFR-Au NRs. In the light-scattering image, the anisotropic structure that comprises the plasmon cloud located on antiEGFR-Au NRs showed greater uptake on the malignant cell line two axes, one on the transverse axis and the other on the longitudinal than on the nonmalignant cells. This is due to the difference in axis. The transverse band oscillates in resonance with high-energy EGFR targeting to the malignant cells and passive uptake in the visible electromagnetic waves at 500 nm and the longitudinal band nonmalignant cells. This was also confirmed by the increase in the oscillates in resonance toward the low-energy NIR range. This extinction intensity measured by comparing the malignant cells with longitudinal range can be tuned by changing the aspect ratio. the nonmalignant cells. In PTT, the malignant cells incubated with Generally, Au NRs synthesized