- PEGylated gold nanoparticles functionalized with β-cyclodextrin inclusion complexes: Towards metal nanoparticle-polymer-carbohydrate cluster biohybrid materials
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A cholesterol-functional trithiocarbonate reversible additionfragmentation chain transfer (RAFT) agent was synthesized and employed to generate well-defined poly(polyethylene glycol) acrylate with cholesterol chain termini using RAFT polymerization. Subsequently, the polymers were grafted onto the surface of gold nanoparticles using the trithiocarbonate functionality to bind to the gold surface. The cholesterol moieties were then modified via complexation with β-cyclodextrin. The step-by-step modification of gold nanoparticles was characterized by dynamic light scattering, attenuated total reflection infrared spectroscopy and surface plasmon resonance analysis. CSIRO 2010.
- Liu, Jingquan,Setijadi, Eki,Liu, Yingkai,Whittaker, Michael R.,Boyer, Cyrille,Davis, Thomas P.
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- Matrix metalloproteinase responsive, proximity-activated polymeric nanoparticles for siRNA delivery
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Small interfering RNA (siRNA) has significant potential to evolve into a new class of pharmaceutical inhibitors, but technologies that enable robust, tissue-specific intracellular delivery must be developed before effective clinical translation can be achieved. A pH-responsive, smart polymeric nanoparticle (SPN) with matrix metalloproteinase (MMP)-7-dependent proximity-activated targeting (PAT) is described here. The PAT-SPN is designed to trigger cellular uptake and cytosolic delivery of siRNA once activated by MMP-7, an enzyme whose overexpression is a hallmark of cancer initiation and progression. The PAT-SPN is composed of a corona-forming polyethylene glycol (PEG) block, an MMP-7-cleavable peptide, a cationic siRNA-condensing block, and a pH-responsive, endosomolytic terpolymer block that drives self-assembly and forms the PAT-SPN core. With this novel design, the PEG corona shields cellular interactions until it is cleaved in MMP-7-rich environments, shifting the SPN ζ-potential from +5.8 to +14.4 mV and triggering a 2.5 fold increase in carrier internalization. The PAT-SPN exhibits pH-dependent membrane disruptive behavior that enables siRNA escape from endo-lysosomal pathways. Intracellular siRNA delivery and knockdown of the model enzyme luciferase in R221A-Luc mammary tumor cells is significantly increased by MMP-7 pre-activation (p 0.05). These combined data indicate that the PAT-SPN provides a promising new platform for tissue-specific, proximity-activated siRNA delivery to MMP-rich pathological environments. Copyright
- Li, Hongmei,Yu, Shann S.,Miteva, Martina,Nelson, Christopher E.,Werfel, Thomas,Giorgio, Todd D.,Duvall, Craig L.
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- Temperature responsive polymer-supported TEMPO: An efficient and recoverable catalyst for the selective oxidation of alcohols
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This study aimed to combine the advantages of homogeneous catalysis and heterogeneous catalysis by immobilizing TEMPO into a water-soluble temperature responsive polymer. The supported TEMPO was water soluble and displayed excellent activity in the selective oxidation of alcohols below the LCST and can be easily recovered.
- Chen, Tao,Xu, Zhenkai,Zhou, Lei,Hua, Laiyu,Zhang, Shuo,Wang, Jiping
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- Precision Epitaxy for Aqueous 1D and 2D Poly(? -caprolactone) Assemblies
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The fabrication of monodisperse nanostructures of highly controlled size and morphology with spatially distinct functional regions is a current area of high interest in materials science. Achieving this control directly in a biologically relevant solvent, without affecting cell viability, opens the door to a wide range of biomedical applications, yet this remains a significant challenge. Herein, we report the preparation of biocompatible and biodegradable poly(? -caprolactone) 1D (cylindrical) and 2D (platelet) micelles in water and alcoholic solvents via crystallization-driven self-assembly. Using epitaxial growth in an alcoholic solvent, we show exquisite control over the dimensions and dispersity of these nanostructures, allowing access to uniform morphologies and predictable dimensions based on the unimer-to-seed ratio. Furthermore, for the first time, we report epitaxial growth in aqueous solvent, achieving precise control over 1D nanostructures in water, an essential feature for any relevant biological application. Exploiting this further, a strong, biocompatible and fluorescent hydrogel was obtained as a result of living epitaxial growth in aqueous solvent and cell culture medium. MC3T3 and A549 cells were successfully encapsulated, demonstrating high viability (>95% after 4 days) in these novel hydrogel materials.
- Arno, Maria C.,Inam, Maria,Coe, Zachary,Cambridge, Graeme,Macdougall, Laura J.,Keogh, Robert,Dove, Andrew P.,O'Reilly, Rachel K.
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- Biomimetic functionalization of carbon nanotubes with poly(ionic liquids) for highly efficient adsorption of organic dyes
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The removal of environmental pollutants from wastewater through adsorption has regarded as one of the most efficient methods. A number of adsorbents based on nanomaterials and their composites have been examined for this purpose. Among them, carbon nanotubes (CNT) should be one of the promising candidates owing to their small size, large π conjugation system and high specific surface areas, however, the performance of CNT for adsorption is largely impeded by their poor dispersibility and lack of functional groups. Therefore, the development of simple and effective surface modification strategies to overcome the above drawbacks should be of great importance for their practical utilization in the environmental fields. In this study, a novel and simple biomimetic method was reported for the first time for surface modification of CNT with poly(ionic liquids) through the combination of mussel-inspired chemistry and subsequent surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization. An ionic liquid ([C16VIm+] [Br?]) was used as the monomer in this work because it is capable of introducing charged functional groups on the surface of CNT and thus boosts their adsorption performance towards environmental pollutants. As a model organic dye, Congo red (CR) was selected as the environmental pollutant and its adsorption behaviors of CR by CNT?IL composites were examined and analyzed in details. The results demonstrated that the adsorption capacity of CNT?IL intake CR (50 mg L?1) was obvious higher than that of unmodified CNT and the adsorption capacity reaches 178 mg g?1 with pH = 7 at 56 min. In addition, adsorption kinetic models and isotherm models were investigated to identify the adsorption kinetic rates and adsorption behavior, respectively. The adsorption principle that including electrostatic interaction, π-π interaction between imidazole rings on the surface of CNT?IL and CR, was proposed. This novel biomimetic surface modification could also be utilized for fabrication of many other functional materials with designable properties and improved performance. Therefore, this work will open up a new research avenue for the fabrication of multifunctional CNT based polymer composites.
- Yang, Guang,Huang, Qiang,Gan, Defu,Huang, Hongye,Chen, Junyu,Deng, Fengjie,Liu, Meiying,Wen, Yuanqing,Zhang, Xiaoyong,Wei, Yen
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- Synthesis of statistical copolymers containing multiple functional peptides for nucleic acid delivery
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Our report describes RAFT copolymerization of multiple species of active peptide monomers with N-(2-hydroxypropyl(methacrylamide) (HPMA) under aqueous conditions. Resulting statistical copolymers are narrowly disperse with highly controlled molecular weight and composition. Side-chain peptide copolymers were synthesized using a DNA condensing peptide (K12), and an endosomal escape peptide (K6H5) that had been modified with an aminohexanoic linker and capped with methacrylamide vinyl on the NH 2-terminus. Copolymers of HMPA-co-K12 and HPMA-co-K 12-co-K6H5 efficiently condensed DNA into small particles that maintain size stability even in 150 mM salt solutions. With increasing peptide content, the peptide-based polymers demonstrated gene delivery efficiencies to HeLa cells that were comparable to branched polyethylenimine.
- Johnson, Russell N.,Burke, Rob S.,Convertine, Anthony J.,Hoffman, Allan S.,Stayton, Patrick S.,Pun, Suzie H.
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- Poly(sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA)
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Poly(sarcosine) (PSar) is a non-ionic hydrophilic polypeptoid with numerous biologically relevant properties, making it an appealing candidate for the development of amphiphilic block copolymer nanostructures. In this work, the fabrication of poly(sarcosine)-based diblock copolymer nano-objects with various morphologies via aqueous reversible addition-fragmentation chain-transfer (RAFT)-mediated photoinitiated polymerization-induced self-assembly (photo-PISA) is reported. Poly(sarcosine) was first synthesized via ring-opening polymerization (ROP) of sarcosine N-carboxyanhydride, using high-vacuum techniques. A small molecule chain transfer agent (CTA) was then coupled to the active ω-amino chain end of the telechelic polymer for the synthesis of a poly(sarcosine)-based macro-CTA. Controlled chain-extensions of a commercially available water-miscible methacrylate monomer (2-hydroxypropyl methacrylate) were achieved via photo-PISA under mild reaction conditions, using PSar macro-CTA. Upon varying the degree of polymerization and concentration of the core-forming monomer, morphologies evolving from spherical micelles to worm-like micelles and vesicles were accessed, as determined by dynamic light scattering and transmission electron microscopy, resulting in the construction of a detailed phase diagram. The resistance of both colloidally stable empty vesicles and enzyme-loaded nanoreactors against degradation by a series of proteases was finally assessed. Overall, our findings underline the potential of poly(sarcosine) as an alternative corona-forming polymer to poly(ethylene glycol)-based analogues of PISA assemblies for use in various pharmaceutical and biomedical applications.
- Varlas, Spyridon,Georgiou, Panagiotis G.,Bilalis, Panayiotis,Jones, Joseph R.,Hadjichristidis, Nikos,O'Reilly, Rachel K.
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- Preparation method of RAFT chain transfer agent with good water solubility
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The invention relates to a preparation method of an RAFT chain transfer agent with good water solubility. The RAFT chain transfer agent is 2-[(2-methoxyethoxy) ethyl]-4-cyano-4-[ethylthio (thiocarbonyl) thio] valerate. The preparation method comprises the following steps: ethanethiol, sodium hydroxide, carbon disulfide, iodine, 4, 4-bisazo-bis (4-cyanovaleric acid), methoxypolyethylene glycol, 4-dimethylaminopyridine and dicyclohexylcarbodiimide are taken as main raw materials, four-step synthesis reaction is performed and finally 2-[(2-methoxyethoxy) ethyl]-4-cyano-4-[ethylthio (thiocarbonyl)thio] valerate with relatively high yield is generated. The RAFT chain transfer agent does not contain long-chain hydrophobic groups, has good water solubility, has the advantages of cheap and easilyavailable raw materials, simple preparation device, easy equipment operation and the like and also has the characteristics of low reaction condition requirements and good proportional reproducibilityand provides economic and stable guarantee for expanded production.
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Paragraph 0046; 0049; 0051; 0054; 0056; 0059; 0061; 0064
(2020/04/29)
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- HYDROPHILIC POLYMER CONJUGATE WITH MULTIPLE ANTIVIRAL AGENTS FOR TREATING A VIRAL INFECTION
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The present invention relates to a hydrophilic polymer conjugate comprising multiple antiviral agents for treating viral infections. The present invention also relates to methods of treating viral infections, in particular, human immunodeficiency virus (HIV) infection, by administration of a hydrophilic polymer conjugate comprising multiple antiviral agents. The polymer conjugates may be useful in combination therapy for the treatment of HIV.
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Page/Page column 71
(2018/01/17)
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- POLYMERIC CARRIER
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Provided herein are polymeric carriers suitable for the delivery of polynucleotides (e.g., oligonucleotides) and/or other therapeutic agents into a living cell.
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Paragraph 0405
(2015/09/28)
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