DOCSLIB.ORG

Polymer–Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Polymer–Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer molecules Article Polymer–Colloid Complexes Based on Cationic Imidazolium Amphiphile, Polyacrylic Acid and DNA Decamer Darya A. Kuznetsova 1 , Dinar R. Gabdrakhmanov 1, Denis M. Kuznetsov 1, Svetlana S. Lukashenko 1, Valery M. Zakharov 2, Anastasiia S. Sapunova 1, Syumbelya K. Amerhanova 1, Anna P. Lyubina 1, Alexandra D. Voloshina 1 , Diana V. Salakhieva 3 and Lucia Ya. Zakharova 1,* 1 FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Institute of Organic and Physical Chemistry, Arbuzov str. 8, 420088 Kazan, Russia; [email protected] (D.A.K.); [email protected] (D.R.G.); [email protected] (D.M.K.); [email protected] (S.S.L.); [email protected] (A.S.S.); [email protected] (S.K.A.); [email protected] (A.P.L.); [email protected] (A.D.V.) 2 Kazan National Research Technological University, Karl Marx str., 68, 420015 Kazan, Russia; [email protected] 3 Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kremlyovskaya St. 18, 420008 Kazan, Russia; [email protected] * Correspondence: [email protected]; Tel.: +7-(843)-273-22-93 Abstract: The solution behavior and physicochemical characteristics of polymer–colloid complexes based on cationic imidazolium amphiphile with a dodecyl tail (IA-12) and polyacrylic acid (PAA) or Citation: Kuznetsova, D.A.; Gabdrakhmanov, D.R.; Kuznetsov, DNA decamer (oligonucleotide) were evaluated using tensiometry, conductometry, dynamic and D.M.; Lukashenko, S.S.; Zakharov, electrophoretic light scattering and fluorescent spectroscopy and microscopy. It has been established V.M.; Sapunova, A.S.; Amerhanova, that PAA addition to the surfactant system resulted in a ca. 200-fold decrease in the aggregation S.K.; Lyubina, A.P.; Voloshina, A.D.; threshold of IA-12, with the hydrodynamic diameter of complexes ranging within 100–150 nm. Salakhieva, D.V.; et al. Electrostatic forces are assumed to be the main driving force in the formation of IA-12/PAA complexes. Polymer–Colloid Complexes Based Factors influencing the efficacy of the complexation of IA-12 with oligonucleotide were determined. on Cationic Imidazolium Amphiphile, The nonconventional mode of binding with the involvement of hydrophobic interactions and the Polyacrylic Acid and DNA Decamer. intercalation mechanism is probably responsible for the IA-12/oligonucleotide complexation, and Molecules 2021, 26, 2363. https:// a minor contribution of electrostatic forces occurred. The latter was supported by zeta potential doi.org/10.3390/molecules26082363 measurements and the gel electrophoresis technique, which demonstrated the low degree of charge neutralization of the complexes. Importantly, cellular uptake of the IA-12/oligonucleotide complex Academic Editors: Ramón G. Rubio and Tamar Greaves was confirmed by fluorescence microscopy and flow cytometry data on the example of M-HeLa cells. While single IA-12 samples exhibit roughly similar cytotoxicity, IA-12–oligonucleotide complexes Received: 2 February 2021 show a selective effect toward M-HeLa cells (IC50 1.1 µM) compared to Chang liver cells (IC50 Accepted: 15 April 2021 23.1 µM). Published: 19 April 2021 Keywords: imidazolium; amphiphile; polyacrylic acid; oligonucleotide; complexation Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Interactions between oppositely charged surfactants and synthetic polyelectrolytes are currently the focus of modern research [1–6]. This is mainly due to the possibility of the control of the properties of these systems by the variation of the chemical struc- Copyright: © 2021 by the authors. ture, ratio and concentration of components, molecular weight of the polymer, pH of the Licensee MDPI, Basel, Switzerland. medium, temperature and ionic strength [7–9]. In addition, the fabrication of complexes This article is an open access article can be mediated by different mechanisms, including the hydrophobic effect, van der Waals distributed under the terms and interactions and hydrogen bonding, with the contribution of dominating electrostatic in- conditions of the Creative Commons teractions [10–13]. For these reasons, mixtures of polyelectrolytes and oppositely charged Attribution (CC BY) license (https:// surfactants are characterized by the complicated behavior of solutions [14–16]. The addi- creativecommons.org/licenses/by/ tion of a high-molecular-weight component can change the aggregation thresholds of the 4.0/). Molecules 2021, 26, 2363. https://doi.org/10.3390/molecules26082363 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x 2 of 17 surfactants are characterized by the complicated behavior of solutions [14–16]. The addi- tion of a high-molecular-weight component can change the aggregation thresholds of the system [17–20]. Moreover, the investigation of polymer–colloid systems allows simulating the interaction of cationic amphiphiles with natural polymers such as DNA, proteins and so on [7,21–23]. This is of importance in gene therapy [24,25] because the application of naked DNA molecules is complicated due to their huge size, the electrostatic repulsion between nucleotides and negatively charged cell membranes and the immune response Molecules 2021, 26, 2363 2 of 17 observed [26]. Therefore, efficient transfection can be achieved using optimized carriers of polynucleotides, which allow compacting large DNA molecules and recharging them. systemThis allows [17–20]. Moreover,genetic material the investigation to be ofrecognized polymer–colloid by the systems cell allows[27,28], simulating pass through the cell themembrane interaction by of cationicthe endocytosis amphiphiles mechanism with natural polymers[29] and such receive as DNA, protection proteins and from biodegrada- sotion. on [ 7From,21–23 this]. This point is of of importance view, cationic in gene surfactants therapy [24,25 are] because among the the application most prospective of carriers naked[30–34 DNA], including molecules isthose complicated bearing due an to theirimidazolium huge size, the moiety electrostatic [35– repulsion38]. Imidazolium am- between nucleotides and negatively charged cell membranes and the immune response phiphiles and DNA were documented to form sustainable nontoxic complexes that pro- observed [26]. Therefore, efficient transfection can be achieved using optimized carriers of polynucleotides,tect from enzymatic which allow degradation compacting large and DNA provide molecules a andcharge recharging density them. sufficient This for DNA allowstransport genetic through material the to be cell recognized membrane by the [35]. cell [27 Nonviral,28], pass throughvectors the based cell membrane on the mixture of lipids byand the imidazolium endocytosis mechanism amphiphiles [29] and were receive reported protection and from were biodegradation. less effective From than this commercially pointavailable of view, lipofectamine cationic surfactants 2000 are; however among the, they most prospectivehad lower carriers toxicity [30 [36].–34], includ- ing those bearing an imidazolium moiety [35–38]. Imidazolium amphiphiles and DNA were documentedA brief literature to form sustainableoverview nontoxicmakes it complexes obvious thatthat protect the fabrication from enzymatic of complexes based degradationon amphiphiles and provide and polyelectrolytes a charge density sufficient of various for DNA types transport is urgent. through Nevertheless, the cell despite the membranelong-term [35 study]. Nonviral of these vectors systems, based onthere the mixtureis little of understanding lipids and imidazolium of the factors am- influencing phiphilestheir functional were reported activity. and were Much less effectiveattention than is commercially paid to the available interaction lipofectamine of cationic surfactants 2000; however, they had lower toxicity [36]. with anionic synthetic polyelectrolytes because they could simulate complexation be- A brief literature overview makes it obvious that the fabrication of complexes based ontween amphiphiles DNA and and polyelectrolytesamphiphilic compounds. of various types Unlike is urgent. strong Nevertheless, polyelectrolytes, despite the weak polyelec- long-termtrolytes studydemonstrate of these systems, complicated there is and little tunable understanding solution of the behavior, factors influencing which is controlled by theirthe charge functional density activity. of Much a polymer attention chain, is paid which to the, interactionin turn, is of determined cationic surfactants by the nature of mac- withromolecules, anionic synthetic concentration polyelectrolytes of charged because theyadditives, could simulate solution complexation pH, etc. For between cationic surfactant– DNA and amphiphilic compounds. Unlike strong polyelectrolytes, weak polyelectrolytes demonstratepolyacrylic complicated acid (PAA) and binary tunable solutionsystems behavior,, the critical which isionization controlled bydegree the charge αc should be taken densityinto account. of a polymer The chain, theoretical which, invalue turn, of is determinedαc = 0.35 can by thebe naturecalculated of macromolecules, based on Manning’s coun- concentrationterion condensation of charged additives,theory [39]. solution Typically, pH, etc. For electrostatic cationic surfactant–polyacrylic interactions prevail above αc, acidwhile (PAA) the binary hydrophobic systems, the effect critical in ionizationcombination degree withαc should hydrogen be taken binding into account. contributes to com- The theoretical value
Load more

Recommended publications
  • Partition Coefficients in Mixed Surfactant Systems
    Partition coefficients in mixed surfactant systems Application of multicomponent surfactant solutions in separation processes Vom Promotionsausschuss der Technischen Universität Hamburg-Harburg zur Erlangung des akademischen Grades Doktor-Ingenieur genehmigte Dissertation von Tanja Mehling aus Lohr am Main 2013 Gutachter 1. Gutachterin: Prof. Dr.-Ing. Irina Smirnova 2. Gutachterin: Prof. Dr. Gabriele Sadowski Prüfungsausschussvorsitzender Prof. Dr. Raimund Horn Tag der mündlichen Prüfung 20. Dezember 2013 ISBN 978-3-86247-433-2 URN urn:nbn:de:gbv:830-tubdok-12592 Danksagung Diese Arbeit entstand im Rahmen meiner Tätigkeit als wissenschaftliche Mitarbeiterin am Institut für Thermische Verfahrenstechnik an der TU Hamburg-Harburg. Diese Zeit wird mir immer in guter Erinnerung bleiben. Deshalb möchte ich ganz besonders Frau Professor Dr. Irina Smirnova für die unermüdliche Unterstützung danken. Vielen Dank für das entgegengebrachte Vertrauen, die stets offene Tür, die gute Atmosphäre und die angenehme Zusammenarbeit in Erlangen und in Hamburg. Frau Professor Dr. Gabriele Sadowski danke ich für das Interesse an der Arbeit und die Begutachtung der Dissertation, Herrn Professor Horn für die freundliche Übernahme des Prüfungsvorsitzes. Weiterhin geht mein Dank an das Nestlé Research Center, Lausanne, im Besonderen an Herrn Dr. Ulrich Bobe für die ausgezeichnete Zusammenarbeit und der Bereitstellung von LPC. Den Studenten, die im Rahmen ihrer Abschlussarbeit einen wertvollen Beitrag zu dieser Arbeit geleistet haben, möchte ich herzlichst danken. Für den außergewöhnlichen Einsatz und die angenehme Zusammenarbeit bedanke ich mich besonders bei Linda Kloß, Annette Zewuhn, Dierk Claus, Pierre Bräuer, Heike Mushardt, Zaineb Doggaz und Vanya Omaynikova. Für die freundliche Arbeitsatmosphäre, erfrischenden Kaffeepausen und hilfreichen Gespräche am Institut danke ich meinen Kollegen Carlos, Carsten, Christian, Mohammad, Krishan, Pavel, Raman, René und Sucre.
    [Show full text]
  • Simple, Self-Assembling, Single-Site Model Amphiphile for Water-Free Simulation of Lyotropic Phases
    Simple, self-assembling, single-site model amphiphile for water-free simulation of lyotropic phases Somajit Dey and Jayashree Saha Department of Physics, University of Calcutta, 92, A.P.C Road, Kolkata-700009, India, Email: [email protected] Computationally, low-resolution coarse-grained models provide the most viable means for simulating the large length and time scales associated with mesoscopic phenomena. Moreover, since lyotropic phases in solution may contain high solvent to amphiphile ratio, implicit solvent models are appropriate for many purposes. By modifying the well-known Gay-Berne potential with an imposed uni-directionality and a longer range, we have come to a simple single-site model amphiphile that can rapidly self-assemble to give diverse lyotropic phases without the explicit incorporation of solvent particles. The model represents a tuneable packing parameter that manifests in the spontaneous curvature of amphiphile aggregates. Apart from large scale simulations (e.g. the study of self-assembly, amphiphile mixing, domain formation etc.) this novel, non-specific model may be useful for suggestive pilot projects with modest computational resources. No such self-assembling, single-site amphiphile model has been reported previously in the literature to the best of our knowledge. 1 Introduction by allowing larger time steps [10]. It also reduces the number of Surfactants or “surface active agents” are so called because of their site-site interactions for a given number of macromolecules ability to reduce the surface tension of liquids. Macromolecules implying a larger length scale. However, the small size of CG water that act as surfactants in water generally consist of a hydrophilic molecules compared to the amphiphiles, combined with their (water-loving) head linked to one or more hydrophobic (water- number, limit the scales of a simulation.
    [Show full text]
  • Self-Assembling Peptides and Their Application in the Treatment of Diseases
    International Journal of Molecular Sciences Review Self-Assembling Peptides and Their Application in the Treatment of Diseases Sungeun Lee 1, Trang H.T. Trinh 1, Miryeong Yoo 1, Junwu Shin 1, Hakmin Lee 1, Jaehyeon Kim 1, Euimin Hwang 2, Yong-beom Lim 2 and Chongsuk Ryou 1,* 1 Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Gyeonggi-do 15588, Korea; [email protected] (S.L.); [email protected] (T.H.T.T.); [email protected] (M.Y.); [email protected] (J.S.); [email protected] (H.L.); [email protected] (J.K.) 2 Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Korea; [email protected] (E.H.); [email protected] (Y.-b.L.) * Correspondence: [email protected]; Tel.: +82-31-400-5811; Fax: +82-31-400-5958 Received: 30 September 2019; Accepted: 20 November 2019; Published: 21 November 2019 Abstract: Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures.
    [Show full text]
  • Review Article Amphiphiles Self-Assembly: Basic Concepts and Future Perspectives of Supramolecular Approaches
    Hindawi Publishing Corporation Advances in Condensed Matter Physics Volume 2015, Article ID 151683, 22 pages http://dx.doi.org/10.1155/2015/151683 Review Article Amphiphiles Self-Assembly: Basic Concepts and Future Perspectives of Supramolecular Approaches Domenico Lombardo,1 Mikhail A. Kiselev,2 Salvatore Magazù,3 and Pietro Calandra4 1 Consiglio Nazionale delle Ricerche (CNR), Istituto per i Processi Chimico-Fisici (IPCF), Viale F.S. D’Alcontres, No. 37, 98158 Messina, Italy 2Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Ulica Joliot-Curie 6, Dubna, Moscow 141980, Russia 3Dipartimento di Fisica e Scienze della Terra, Universita` di Messina, Viale F.S. D’Alcontres, No. 31, 98158 Messina, Italy 4Consiglio Nazionale delle Ricerche (CNR), Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), Via Salaria km 29.300, Monterotondo Stazione, 00015 Roma, Italy Correspondence should be addressed to Domenico Lombardo; [email protected] Received 5 May 2015; Accepted 27 September 2015 Academic Editor: Ram N. P. Choudhary Copyright © 2015 Domenico Lombardo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Amphiphiles are synthetic or natural molecules with the ability to self-assemble into a wide variety of structures including micelles, vesicles, nanotubes, nanofibers, and lamellae. Self-assembly processes of amphiphiles have been widely used to mimic biological systems, such as assembly of lipids and proteins, while their integrated actions allow the performance of highly specific cellular functions which has paved a way for bottom-up bionanotechnology.
    [Show full text]
  • Amphiphile Regulation of Ion Channel Function by Changes in the Bilayer Spring Constant
    Amphiphile regulation of ion channel function by changes in the bilayer spring constant Jens A. Lundbæka,b,1, Roger E. Koeppe IIc, and Olaf S. Andersena aDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065; bQuantum Protein Center, Department of Physics, Technical University of Denmark, Kongens Lyngby, DK-2800, Denmark; and cDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701 Edited* by Christopher Miller, Brandeis University, Waltham, MA, and approved July 16, 2010 (received for review June 1, 2010) Many drugs are amphiphiles that, in addition to binding to a A B particular target protein, adsorb to cell membrane lipid bilayers and alter intrinsic bilayer physical properties (e.g., bilayer thick- ness, monolayer curvature, and elastic moduli). Such changes can modulate membrane protein function by altering the energetic F ΔG dis cost ( bilayer) of bilayer deformations associated with protein conformational changes that involve the protein-bilayer interface. d l d l But amphiphiles have complex effects on the physical properties of 0 0 ΔG lipid bilayers, meaning that the net change in bilayer cannot be F predicted from measurements of isolated changes in such proper- dis ties. Thus, the bilayer contribution to the promiscuous regulation Fig. 1. Hydrophobic coupling between a bilayer-embedded protein and its of membrane proteins by drugs and other amphiphiles remains host lipid bilayer. (A) A protein conformational change causes a local bilayer unknown. To overcome this problem, we use gramicidin A (gA) deformation. (B) Formation of a gA channel involves local bilayer thinning. channels as molecular force probes to measure the net effect of Modified from ref.
    [Show full text]
  • Solubility Limits and Phase Diagrams for Fatty Acids in Anionic (SLES) and Zwitterionic (CAPB) Micellar Surfactant Solutions ⇑ Sylvia S
    Journal of Colloid and Interface Science 369 (2012) 274–286 Contents lists available at SciVerse ScienceDirect Journal of Colloid and Interface Science www.elsevier.com/locate/jcis Solubility limits and phase diagrams for fatty acids in anionic (SLES) and zwitterionic (CAPB) micellar surfactant solutions ⇑ Sylvia S. Tzocheva a, Peter A. Kralchevsky a, , Krassimir D. Danov a, Gergana S. Georgieva a, Albert J. Post b, Kavssery P. Ananthapadmanabhan b a Department of Chemical Engineering, Faculty of Chemistry, Sofia University, 1164 Sofia, Bulgaria b Unilever Research and Development, Trumbull, CT 06611, USA article info abstract Article history: The limiting solubility of fatty acids in micellar solutions of the anionic surfactant sodium laurylethersul- Received 17 October 2011 fate (SLES) and the zwitterionic surfactant cocamidopropyl betaine (CAPB) is experimentally determined. Accepted 12 December 2011 Saturated straight-chain fatty acids with n = 10, 12, 14, 16, and 18 carbon atoms were investigated at Available online 22 December 2011 working temperatures of 25, 30, 35, and 40 °C. The rise of the fatty acid molar fraction in the micelles is accompanied by an increase in the equilibrium concentration of acid monomers in the aqueous phase. Keywords: Theoretically, the solubility limit is explained with the precipitation of fatty acid crystallites when the Solubility limit of fatty acids monomer concentration reaches the solubility limit of the acid in pure water. In agreement with theory, Fatty acids in surfactant micelles the experiment shows that the solubility limit is proportional to the surfactant concentration. For ideal Solubilization energy CMC for mixed micelles mixtures, the plot of the log of solubility limit vs.
    [Show full text]
  • Influence of Phase Properties and Amphiphile Head Group
    BBRC Biochemical and Biophysical Research Communications 296 (2002) 596–603 www.academicpress.com Solubility of amphiphiles in membranes: influence of phase properties and amphiphile head groupq Luııs M.B.B. Estronca,a Maria Joaao~ Moreno,a Magda S.C. Abreu,a Eurico Melo,b,c and Winchil L.C. Vaza,* a Departamento de Quıımica, Universidade de Coimbra, Coimbra 3004-535, Portugal b Institute de Tecnologia Quıımica e Biologica, Universidade Nova de Lisboa, Oeiras 2784-505, Portugal c Institute Superior Tecnico, Lisboa 1049-001, Portugal Received 17 July 2002 Abstract The solubilities of two fluorescent lipid amphiphiles with comparable apolar structures and different polar head groups, NBD- hexadecylamine and RG-tetradecylamine (or -octadecylamine), were compared in lipid bilayers at a molar ratio of 1/50 at 23 °C. Bilayers examined were in the solid, liquid-disordered, or liquid-ordered phases. While NBD-hexadecylamine was soluble in all the examined bilayer membrane phases, RG-tetradecylamine was stably soluble only in the liquid-disordered phase. RG-tetradecyl- amine insolubility in solid and liquid-ordered phases manifests itself as an aggregation of the amphiphile over a period of several days and the kinetics of aggregation were studied. Solubility of these amphiphiles in the different phases examined seems to be related to the dipole moment of the amphiphile (in particular, of the polar fluorophore) and its orientation relative to the dipolar potential of the membrane. We propose that amphiphilic molecules inserted into membranes (including lipid-attached proteins) partition into different coexisting membrane phases based upon: (1) nature of the apolar structure (chain length, degree of satu- ration, and chain branching as has been proposed in the literature); (2) magnitude and orientation of the dipole moment of the polar portion of the molecules relative to the membrane dipolar potential; and (3) hydration forces that are a consequence of ordering of water dipoles at the membrane surface.
    [Show full text]
  • Solubilization of Itraconazole by Surfactants and Phospholipid-Surfactant Mixtures: Interplay of Amphiphile Structure, Ph and Electrostatic T Interactions
    Journal of Drug Delivery Science and Technology 57 (2020) 101688 Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst Solubilization of itraconazole by surfactants and phospholipid-surfactant mixtures: interplay of amphiphile structure, pH and electrostatic T interactions ∗ Zahari Vinarova, , Gabriela Ganchevaa, Nikola Burdzhievb, Slavka Tcholakovaa a Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, 1164, Sofia, Bulgaria b Department of Organic Chemistry and Pharmacognosy, Faculty of Chemistry and Pharmacy, Sofia University, 1164, Sofia, Bulgaria ARTICLE INFO ABSTRACT Keywords: Although surfactants are frequently used in enabling formulations of poorly water-soluble drugs, the link be- Itraconazole tween their structure and drug solubilization capacity is still unclear. We studied the solubilization of the “brick- Poorly water-soluble drugs dust” molecule itraconazole by 16 surfactants and 3 phospholipid:surfactant mixtures. NMR spectroscopy was Solubilization used to study in more details the drug-surfactant interactions. Very high solubility of itraconazole (up to 3.6 g/L) Surfactants was measured in anionic surfactant micelles at pH = 3, due to electrostatic attraction between the oppositely Phospholipids charged (at this pH) drug and surfactant molecules. 1H NMR spectroscopy showed that itraconazole is ionized at Electrostatic interactions two sites (2+ charge) at these conditions: in the phenoxy-linked piperazine nitrogen and in the dioxolane-linked triazole ring. The increase of amphiphile hydrophobic chain length had a markedly different effect, depending on the amphiphile type: the solubilization capacity of single-chain surfactants increased, whereas a decrease was observed for double-chained surfactants (phosphatidylglycerols). The excellent correlation between the chain melting temperatures of phosphatidylglycerols and itraconazole solubilization illustrated the importance of hydrophobic chain mobility.
    [Show full text]
  • Novel Cationic Amphiphiles As Delivery Agents for Antisense Oligonucleotides R
    3334–3341 Nucleic Acids Research, 1999, Vol. 27, No. 16 © 1999 Oxford University Press Novel cationic amphiphiles as delivery agents for antisense oligonucleotides R. K. DeLong1, Hoon Yoo1,S.K.Alahari1,M.Fisher1,S.M.Short1,S.H.Kang2,R.Kole1,2, V. Janout3,S.L.Regan3 and R. L. Juliano1,* 1Department of Pharmacology and 2Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA and 3Department of Chemistry, Lehigh University, Bethlehem, PA 18015, USA Received as resubmission April 19, 1999; Revised and Accepted May 7, 1999 ABSTRACT INTRODUCTION There has been great interest recently in therapeutic Currently there is substantial interest in the use of antisense use of nucleic acids including genes, ribozymes and oligonucleotides, ribozymes, high molecular weight DNA and antisense oligonucleotides. Despite recent improve- other types of nucleic acids to modify gene expression for ments in delivering antisense oligonucleotides to therapeutic purposes (1–5). Antisense oligonucleotides are cells in culture, nucleic acid-based therapy is still usually administered in vitro or in vivo either in free form or often limited by the poor penetration of the nucleic complexed with various cationic lipid-based formulations (6–9). acid into the cytoplasm and nucleus of cells. In this Gene therapy has primarily relied on viral vectors (1), but there report we describe nucleic acid delivery to cells is increasing interest in use of non-viral gene delivery systems based on lipids, polymers or combinations of both (10–14). using a series of novel cationic amphiphiles containing The ability of a nucleic acid to achieve a desired function cholic acid moieties linked via alkylamino side within cells is influenced by several critical factors in addition chains.
    [Show full text]
  • Terminal Aspartic Acids Promote the Self-Assembly of Collagen Mimic
    RSC Advances View Article Online PAPER View Journal | View Issue Terminal aspartic acids promote the self-assembly of collagen mimic peptides into nanospheres† Cite this: RSC Adv.,2018,8,2404 Linyan Yao,a Manman He,a Dongfang Li,a Jing Tian,a Huanxiang Liu b and Jianxi Xiao *a The development of novel strategies to construct collagen mimetic peptides capable of self-assembling into higher-order structures plays a critical role in the discovery of functional biomaterials. We herein report the construction of a novel type of amphiphile-like peptide conjugating the repetitive triple helical (GPO)m sequences characteristic of collagen with terminal hydrophilic aspartic acids. The amphiphile- like collagen mimic peptides containing a variable length of (Gly-Pro-Hyp)m sequences consistently generate well-ordered nanospherical supramolecular structures. The C-terminal aspartic acids have been revealed to play a determinant role in the appropriate self-assembly of amphiphile-like collagen mimic peptides. Their presence is a prerequisite for self-assembly, and their lengths could modulate the morphology of final assemblies. We have demonstrated for the first time that amphiphile-like collagen Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Received 27th October 2017 mimic peptides with terminal aspartic acids may provide a general and convenient strategy to create Accepted 3rd January 2018 well-defined nanostructures in addition to amphiphile-like peptides utilizing b-sheet or a-helical coiled- DOI: 10.1039/c7ra11855d coil motifs. The newly developed assembly strategy together with the ubiquitous natural function of rsc.li/rsc-advances collagen may lead to the generation of novel improved biomaterials.
    [Show full text]
  • The Binary Mixtures
    UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC T H E S E pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Chimie et Physicochimie des Matériaux (CNU 31) Ecole Doctorale : Sciences Chimiques (ED 459) Soutenue Le 10 juin 2011 par Caroline Bauer Metal ion extractant in microemulsions: where solvent extraction and surfactant science meet Composition du jury Prof. Jean-Francois Dufrêche Président du jury Prof. Gérard Cote ENSCP, France Rapporteur Prof. Kenneth Nash Washington State University, USA Rapporteur Dr. Julian Oberdisse CNRS/UM2, France Examinateur Dr. Jean-Claude Maurel Medesis Pharma, France Examinateur Prof. Jean-Francois Dufrêche ICSM/UM2, France Examinateur Prof. Thomas Zemb ICSM, France Directeur de thèse Dr. Olivier Diat CEA, France Invité Dr. Marie-Christine Charbonnel CEA, France Invité Acknowledgements This thesis would not have been possible unless the support and participation of many people. I am heartily thankful to my advisor, Pr. Thomas Zemb, whose encouragement, guidance and invaluable support from the initial to the final level enabled me to develop an understanding of the subject. I owe my deepest gratitude to Dr. Olivier Diat, for his perpetual advice, supervision and crucial contribution which made him a backbone of this research and so to this thesis. Pr. Kenneth Nash and Pr. Gérard Cote for their interest in that work and accepting to read and critically evaluate the manuscript as it is the role of the “rapporteurs”, I would like to thank heartfully. I am furthermore grateful to the other members of the jury, the “examinateurs”, Dr. Jean-Claude Maurel, Dr. Julian Oberdisse, Prof.
    [Show full text]
  • Formation and Stability of Prebiotically Relevant Vesicular Systems in Terrestrial Geothermal Environments
    Article Formation and Stability of Prebiotically Relevant Vesicular Systems in Terrestrial Geothermal Environments Manesh Prakash Joshi 1, Anupam Samanta 2, Gyana Ranjan Tripathy 2 and Sudha Rajamani 1,* 1 Department of Biology, Indian Institute of Science Education and Research, Pune 411008, India; [email protected] 2 Department of Earth and Climate Science, Indian Institute of Science Education and Research, Pune 411008, India; [email protected] (A.S.); [email protected] (G.R.T.) * Correspondence: [email protected]; Tel.: +91-20-2590-8061 Received: 21 October 2017; Accepted: 28 November 2017; Published: 30 November 2017 Abstract: Terrestrial geothermal fields and oceanic hydrothermal vents are considered as candidate environments for the emergence of life on Earth. Nevertheless, the ionic strength and salinity of oceans present serious limitations for the self-assembly of amphiphiles, a process that is fundamental for the formation of first protocells. Consequently, we systematically characterized the efficiency of amphiphile assembly, and vesicular stability, in terrestrial geothermal environments, both, under simulated laboratory conditions and in hot spring water samples (collected from Ladakh, India, an Astrobiologically relevant site). Combinations of prebiotically pertinent fatty acids and their derivatives were evaluated for the formation of vesicles in aforesaid scenarios. Additionally, the stability of these vesicles was characterized over multiple dehydration-rehydration cycles, at elevated temperatures. Among the combinations that were tested, mixtures of fatty acid and its glycerol derivatives were found to be the most robust, also resulting in vesicles in all of the hot spring waters that were tested. Importantly, these vesicles were stable at high temperatures, and this fatty acid system retained its vesicle forming propensity, even after multiple cycles of dehydration-rehydration.
    [Show full text]