Synthesis of siRNA Polyplexes Adopting a Combination of RAFT Polymerization and Thiol-ene Chemistry

2009 ◽  
Vol 62 (10) ◽  
pp. 1344 ◽  
Author(s):  
David Valade ◽  
Cyrille Boyer ◽  
Thomas P. Davis ◽  
Volga Bulmus
Keyword(s):  
Block Copolymers ◽  
High Efficiency ◽  
Raft Polymerization ◽  
Hydrodynamic Diameter ◽  
Small Interfering Rnas ◽  
Buffer Solution ◽  
Polyelectrolyte Complexes ◽  
Reversible Addition ◽  
Hydroxypropyl Methacrylamide ◽  
Cationic Copolymers

Block copolymers of allyl methacrylate and N-(2-hydroxypropyl)methacrylamide (HPMA) with different block lengths have been synthesized by reversible addition–fragmentation chain transfer polymerization. Allyl groups were modified with cysteamine, via a thiol-ene photoreaction, with a high efficiency (~100%) as evidenced by NMR spectroscopy, yielding cationic copolymers of HPMA. Polyelectrolyte complexes of small interfering RNAs (siRNA) and the cationic block copolymers were then formed at an N/P ratio between 1 and 4 depending on the block length of the copolymers. Increasing the length of the hydrophilic block was found to decrease the efficiency of siRNA complexation. The hydrodynamic diameter of the polyplexes in 130 mM buffer solution was less than 100 nm.

scholarly journals Photo-Responsive Polymersomes as Drug Delivery System for Potential Medical Applications

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5147
Author(s):  
Wanting Hou ◽  
Ruiqi Liu ◽  
Siwei Bi ◽  
Qian He ◽  
Haibo Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Block Copolymers ◽  
Drug Delivery System ◽  
Delivery System ◽  
Raft Polymerization ◽  
Amphiphilic Block Copolymers ◽  
Medical Applications ◽  
Drug Molecules ◽  
Reversible Addition ◽  
Raft Agent

Due to a strong retardation effect of o-nitrobenzyl ester on polymerization, it is still a great challenge to prepare amphiphilic block copolymers for polymersomes with a o-nitrobenzyl ester-based hydrophobic block. Herein, we present one such solution to prepare amphiphilic block copolymers with pure poly (o-nitrobenzyl acrylate) (PNBA) as the hydrophobic block and poly (N,N’-dimethylacrylamide) (PDMA) as the hydrophilic block using bulk reversible addition-fragmentation chain transfer (RAFT) polymerization of o-nitrobenzyl acrylate using a PDMA macro-RAFT agent. The developed amphiphilic block copolymers have a suitable hydrophobic/hydrophilic ratio and can self-assemble into photoresponsive polymersomes for co-loading hydrophobic and hydrophilic cargos into hydrophobic membranes and aqueous compartments of the polymersomes. The polymersomes demonstrate a clear photo-responsive characteristic. Exposure to light irradiation at 365 nm can trigger a photocleavage reaction of o-nitrobenzyl groups, which results in dissociation of the polymersomes with simultaneous co-release of hydrophilic and hydrophobic cargoes on demand. Therefore, these polymersomes have great potential as a smart drug delivery nanocarrier for controllable loading and releasing of hydrophilic and hydrophobic drug molecules. Moreover, taking advantage of the conditional releasing of hydrophilic and hydrophobic drugs, the drug delivery system has potential use in medical applications such as cancer therapy.

scholarly journals Synthesis of Poly(lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) Copolymers with Controllable Block Structures via Reversible Addition Fragmentation Polymerization from Aminolyzed Poly(lactic acid)

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Wenwen Yu ◽  
Lijing Zhu ◽  
Jiangao Shi ◽  
Cunting Zhao
Keyword(s):  
Lactic Acid ◽  
Block Copolymers ◽  
Raft Polymerization ◽  
Poly Lactic Acid ◽  
Pseudo First Order Reaction ◽  
Oh Groups ◽  
Dimethylaminoethyl Methacrylate ◽  
Reversible Addition ◽  
Raft Agent ◽  
Different Temperatures

Poly(lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) (PLA-PDMAEMA) copolymers were synthesized from aminolyzed PLA via reversible addition fragmentation (RAFT) polymerization. PLA undergoes aminolytic degradation with ethylenediamine (EDA). The kinetics of the aminolysis reaction of PLA at different temperatures and EDA concentrations was investigated in detail. The molar masses of products rapidly decreased in the initial stage at low aminolytic degree. Meanwhile, reactive –NH2 and –OH groups were introduced to the end of shorter PLA chains and used as sites to further immobilize the RAFT agent. PLA-PDMAEMA block copolymers were synthesized. A pseudo-first-order reaction kinetics was observed for the RAFT polymerization of PDMAEMA at a low conversion. By controlling the aminolysis reaction of PLA and RAFT polymerization degree of DMAEMA, the length distributions of the PLA and PDMAEMA blocks can be controlled. This method can be extended to more systems to obtain block copolymers with controllable block structure.

Analysis of Thiol-sensitive Core-cross-linked Polymeric Micelles Carrying Nucleoside Pendant Groups using 'On-line' Methods: Effect of Hydrophobicity on Cross-linking and Degradation

2011 ◽  
Vol 64 (6) ◽  
pp. 766 ◽  
Author(s):  
Bianca M. Blunden ◽  
Donald S. Thomas ◽  
Martina H. Stenzel
Keyword(s):  
Block Copolymers ◽  
Polymeric Micelles ◽  
Raft Polymerization ◽  
Amphiphilic Block Copolymers ◽  
Cross Linking ◽  
Copolymer Composition ◽  
Reversible Addition ◽  
On Line ◽  
Styrene Content ◽  
Poly Ethylene

Amphiphilic block copolymers were prepared via reversible–addition fragmentation chain transfer (RAFT) polymerization and their synthesis, cross-linking, and degradation were studied using on-line monitoring. The focus of this work is the systematic alteration of the hydrophobic block using copolymers based on 5′-O-methacryloyluridine (MAU) and styrene at different compositions to determine the effect of the copolymer composition on the properties of the micelle. A poly(poly(ethylene glycol) methyl ether methacrylate) (PEGMA) macroRAFT agent was chain extended with a mixture of styrene and MAU. In both systems, an increasing fraction of styrene was found to reduce the rate of polymerization, but the functionality of the RAFT system was always maintained. The amphiphilic block copolymers were dialyzed against water to generate micelles with sizes between 17 and 25 nm according to dynamic light scattering (DLS). Increasing styrene content lead to smaller micelles (determined by DLS and transmission electron microscopy) and to lower critical micelle concentrations, which was measured using surface tensiometry. The micelles were further stabilized via core-cross-linking using bis(2-methacroyloxyethyl) disulfide as crosslinker. NMR analysis revealed a faster consumption of crosslinker with higher styrene content. These stable cross-linked micelles were investigated regarding their ability to degrade in the presence of dithiothreitol as a model reductant. Increasing the styrene content resulted in a faster degradation of the cross-linked micelles into unimers.

RAFT Polymerization of Monomers with Highly Disparate Reactivities: Use of a Single RAFT Agent and the Synthesis of Poly(styrene-block-vinyl acetate)

2013 ◽  
Vol 66 (12) ◽  
pp. 1564 ◽  
Author(s):  
Lily A. Dayter ◽  
Kate A. Murphy ◽  
Devon A. Shipp
Keyword(s):  
Block Copolymers ◽  
Vinyl Acetate ◽  
Chain Transfer ◽  
Raft Polymerization ◽  
Good Control ◽  
Scanning Calorimetry ◽  
Styrene Polymerization ◽  
Reversible Addition ◽  
Raft Agent ◽  
End Group

A single reversible addition–fragmentation chain transfer (RAFT) agent, malonate N,N-diphenyldithiocarbamate (MDP-DTC) is shown to successfully mediate the polymerization of several monomers with greatly differing reactivities in radical/RAFT polymerizations, including both vinyl acetate and styrene. The chain transfer constants (Ctr) for MDP-DTC for both these monomers were evaluated; these were found to be ~2.7 in styrene and ~26 in vinyl acetate, indicating moderate control over styrene polymerization and good control of vinyl acetate polymerization. In particular, the MDP-DTC RAFT agent allowed for the synthesis of block copolymers of these two monomers without the need for protonation/deprotonation switching, as has been previously developed with N-(4-pyridinyl)-N-methyldithiocarbamate RAFT agents, or other end-group transformations. The thermal properties of the block copolymers were studied using differential scanning calorimetry, and those with sufficiently high molecular weight and styrene composition appear to undergo phase separation. Thus, MDP-DTC may be useful for the production of other block copolymers consisting of monomers with highly dissimilar reactivities.

scholarly journals Bio-Inspired Amphiphilic Block-Copolymers Based on Synthetic Glycopolymer and Poly(Amino Acid) as Potential Drug Delivery Systems

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 183 ◽  
Author(s):  
Mariia Levit ◽  
Natalia Zashikhina ◽  
Alena Vdovchenko ◽  
Anatoliy Dobrodumov ◽  
Natalya Zakharova ◽  
...  
Keyword(s):  
Amino Acid ◽  
Block Copolymers ◽  
Raft Polymerization ◽  
Amphiphilic Block Copolymers ◽  
Breast Adenocarcinoma ◽  
Hydrodynamic Diameter ◽  
Amphiphilic Copolymers ◽  
Lung Carcinoma Cells ◽  
Biodegradable Poly ◽  
Human Lung Carcinoma

In this work, a method to prepare hybrid amphiphilic block copolymers consisting of biocompatible synthetic glycopolymer with non-degradable backbone and biodegradable poly(amino acid) (PAA) was developed. The glycopolymer, poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Two methods for modifying the terminal dithiobenzoate-group of PMAG was investigated to obtain the macroinitiator bearing a primary aliphatic amino group, which is required for ring-opening polymerization of N-carboxyanhydrides of hydrophobic α-amino acids. The synthesized amphiphilic block copolymers were carefully analyzed using a set of different physico-chemical methods to establish their composition and molecular weight. The developed amphiphilic copolymers tended to self-assemble in nanoparticles of different morphology that depended on the nature of the hydrophobic amino acid present in the copolymer. The hydrodynamic diameter, morphology, and cytotoxicity of polymer particles based on PMAG-b-PAA were evaluated using dynamic light scattering (DLS) and transmission electron microscopy (TEM), as well as CellTiter-Blue (CTB) assay, respectively. The redox-responsive properties of nanoparticles were evaluated in the presence of glutathione taken at different concentrations. Moreover, the encapsulation of paclitaxel into PMAG-b-PAA particles and their cytotoxicity on human lung carcinoma cells (A549) and human breast adenocarcinoma cells (MCF-7) were studied.

Synthetic Polyampholytes Based Cryoprotective Agents by Reversible Addition Fragmentation Chain Transfer Polymerisation

2013 ◽  
Vol 1499 ◽  
Author(s):  
Robin Rajan ◽  
Kazuaki Matsumura
Keyword(s):  
Chain Transfer ◽  
High Efficiency ◽  
Raft Polymerization ◽  
Freezing And Thawing ◽  
Cryoprotective Agents ◽  
Reversible Addition ◽  
Raft Agent ◽  
High Cytotoxicity ◽  
Methylpropionic Acid ◽  
Polymerization Method

ABSTRACTDimethyl sulfoxide (DMSO) and several naturally occurring polyols or their derivatives (like glycerol) have been used as cryoprotective agents (CPAs) for many years. However DMSO shows high cytotoxicity and affects differentiation of cells, so it needs to be removed immediately after thawing, whereas polyols are comparatively weaker cryoprotective agents. Furthermore, some types of cells are extremely sensitive to damage during freezing and thawing, so cannot be cryopreserved properly using current CPAs. So there is a great need to develop newer cryoprotective agents with lower cytotoxicity and high efficiency for many biological and medical purposes.Recently we showed that carboxylated poly-L-lysine, which is classified as a polyampholyte, has a cryoprotective effect on cells in solution without any other cryoprotectant. Polyampholytes are charged polymers with both positively and negatively charged groups.Therefore, in this research, we are developing a completely synthetic polyampholytes by radical polymerization and will try to elucidate the key parameters of cryoprotective properties. Here we chose reversible addition fragmentation chain transfer (RAFT) polymerization as the mode of polymerization as it is a kind of living polymerization method and can give control over the molecular weight and composition of the copolymer. We evaluated the livingness of the 1:1 copolymer with methacrylic acid (MAA) and 2-Dimethylamino ethyl methacrylate (DMAEMA) with 2-(Dodecylthiocarbonothioylthio)-2-methylpropionic acid as the RAFT agent and the polymer solution showed good cell viability of L929 cells after cryopreservation at 15% copolymer concentration.

Synthesis and Solution-state Assembly or Bulk State Thiol-ene Crosslinking of Pyrrolidinone- and Alkene-functionalized Amphiphilic Block Fluorocopolymers: From Functional Nanoparticles to Anti-fouling Coatings

2010 ◽  
Vol 63 (8) ◽  
pp. 1159 ◽  
Author(s):  
Jun Ma ◽  
Jeremy W. Bartels ◽  
Zhou Li ◽  
Ke Zhang ◽  
Chong Cheng ◽  
...  
Keyword(s):  
Block Copolymers ◽  
Diblock Copolymers ◽  
Raft Polymerization ◽  
Building Blocks ◽  
Ene Reactions ◽  
Reversible Addition ◽  
Complex Building ◽  
Crosslinked Networks ◽  
Amphiphilic Diblock Copolymers ◽  
Synthetic Methodologies

With an ever increasing interest in the combined functionality and versatility of materials, increasing demands are placed on synthetic methodologies by which to produce such materials. This work demonstrates the preparation of block copolymers having fluorocarbon content, pyrrolidinone units, and alkene groups as complex building blocks for the assembly of discrete nanoparticles in solution and, alternatively, transformation into sophisticated crosslinked networks. Reversible addition–fragmentation chain transfer (RAFT) polymerization is a facile tool for the synthesis of well-defined polymers containing imbedded side-chain functionalities. In this work, the synthesis of well-defined multifunctional fluorinated polymers bearing pendant pyrrolidinone groups, and block copolymers bearing both pyrrolidinone and alkenyl groups on different segments was achieved, by using RAFT polymerizations of unique bifunctional monomers. Upon micellization, the amphiphilic diblock copolymers were transformed into regioselectively-functionalized nanoparticles. Further transformations of pyrrolidinone- and alkene-dual functionalized-block copolymers into complex amphiphilic networks were accomplished by highly efficient UV-induced thiol-ene reactions. Whether as discrete nanoparticles or nanoscopically-segregated crosslinked networks, these materials have great potential for several diverse technologies, including as anti-fouling materials.

scholarly journals Synthesis of Terpyridine-Terminated Amphiphilic Block Copolymers and Their Self-Assembly into Metallo-Polymer Nanovesicles

Materials ◽  
2019 ◽  
Vol 12 (4) ◽  
pp. 601 ◽  
Author(s):  
Tatyana Elkin ◽  
Stacy Copp ◽  
Ryan Hamblin ◽  
Jennifer Martinez ◽  
Gabriel Montaño ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Block Copolymers ◽  
Self Assembly ◽  
Chain Transfer ◽  
Raft Polymerization ◽  
Amphiphilic Block Copolymers ◽  
Transmission Electron ◽  
Reversible Addition ◽  
Efficient Route ◽  
High Yields

Polystyrene-b-polyethylene glycol (PS-b-PEG) amphiphilic block copolymers featuring a terminal tridentate N,N,N-ligand (terpyridine) were synthesized for the first time through an efficient route. In this approach, telechelic chain-end modified polystyrenes were produced via reversible addition-fragmentation chain-transfer (RAFT) polymerization by using terpyridine trithiocarbonate as the chain-transfer agent, after which the hydrophilic polyethylene glycol (PEG) block was incorporated into the hydrophobic polystyrene (PS) block in high yields via a thiol-ene process. Following metal-coordination with Mn2+, Fe2+, Ni2+, and Zn2+, the resulting metallo-polymers were self-assembled into spherical, vesicular nanostructures, as characterized by dynamic light scattering and transmission electron microscopy (TEM) imaging.

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