Corona-Stabilized Interpolyelectrolyte Complexes of SiRNA with Nonimmunogenic, Hydrophilic/Cationic Block Copolymers Prepared by Aqueous RAFT Polymerization

Scales, Charles W.; Huang, Faqing; Li, Na; Vasilieva, Yulia A.; Ray, Jacob G.; Convertine, A; McCormick, Charles L.

doi:10.1021/ma061453c

Cited by 85 publications

(114 citation statements)

References 96 publications

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“…Beetle Luciferin and heparin sodium salt were bought from Sigma-Aldrich Laborchemikalien GmbH (Seelze, Germany 4-Cyanopentanoic acid dithiobenzoate (CPT), used as chain transfer agent (CTA), was synthesized as described in the literature [29]. The synthesis of pDMAEMA, which was used as a macroCTA, was performed similarly to the method of Scales et al [28]. Briefly, 80 mmol of DMAEMA were mixed in an ice bath with sodium acetate buffer (pH 5.2) and adjusted to pH 5 with HCl.…”

Section: Methodsmentioning

confidence: 99%

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

et al. 2011

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Abstract:The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl amino)ethyl methacrylate) (pDMAEMA) and poly(2-hydroxyethyl methacrylate) (pHEMA). Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a library of linear poly(2-(dimethyl amino)ethyl methacrylate-block-poly(2-hydroxyl methacrylate) (pDMAEMA-block-pHEMA) copolymers was synthesized via RAFT (reversible additionfragmentation chain transfer) polymerization in a molecular weight (Mw) range of 17-35.7 kDa and analyzed using 1 H and 13 C NMR (nuclear magnetic resonance), ATR (attenuated total reflectance), GPC (gel permeation chromatography) and DSC (differential scanning calorimetry). Copolymers possessing short pDMAEMA-polycation chains were 1.4-9.7 times less toxic in vitro than polyethylenimine (PEI) 25 kDa, and complexed DNA into polyplexes of 100-170 nm, favorable for cellular uptake. The DNA-binding affinity and polyplex stability against competing polyanions was comparable with OPEN ACCESSPolymers 2011, 3 694 PEI 25 kDa. The zeta-potential of polyplexes of pDMAEMA-grafted copolymers remained positive (+15-30 mV). In comparison with earlier reported low molecular weight homo pDMAEMA vectors, these diblock-copolymers showed enhanced transfection efficacy under in vitro conditions due to their lower cytotoxicity, efficient cellular uptake and DNA packaging. The homo pDMAEMA 115 (18.3 kDa) self-assembled with DNA into small positively charged polyplexes, but was not able to transfect cells. The grafting of 6 and 57 repeating units of pHEMA (0.8 and 7.4 kDa) to pDMAEMA 115 increased the transfection efficacy significantly, implying a crucial impact of pHEMA on vector-cell interactions. The intracellular trafficking, in vivo transfection efficacy and kinetics of low molecular weight pDMAEMA-block-pHEMA are subject of ongoing studies.

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Section: Methodsmentioning

confidence: 99%

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

et al. 2011

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“…Chitosan, in addition to its cationic characteristic, is a biodegradable, biocompatible, less immunogenic and safe biopolymer. In spite of viral vectors have high transduction efficiency, they have serious problems such as potential mutation, recombination and oncogenic effects and beside this lipid-based non-viral vectors have also serious problems like toxicity and stability [23,24].…”

Section: Pdgf Family Consist Of 4 Different Pdgf Chains (-A -B -C -D)mentioning

confidence: 99%

In vitro gene silencing effect of chitosan/shRNA PDGF-D nanoparticles in breast cancer

Ekentok¹,

Turan²,

Akbuğa³

2017

mpj

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Breast cancer is the most common cancer worldwide in women and it is highly malignant and fatal. PDGF-D plays role in regulation of many cellular processes such as angiogenesis. PDGF-D is overexpressed in many types of cancers and promote tumor growth and metastasis. Silencing of PDGF-D gene by using shRNA with an appropriate carrier system may decrease tumor growth and metastasis. In our study, we prepared chitosan nanoparticles loaded with five different shRNA plasmids targeting different exons of PDGF-D gene. Then, nanoparticles were characterized in vitro and transfection efficiency of these nanoparticles were investigated in breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-435). The effects of single and multiple shRNA sequences, molecular weight of chitosan (150 kDa and 400 kDa) and the amount of shRNA (100 and 500 µg) on the characterization and transfection efficiencies of nanoparticles have been studied. Size of nanoparticles changed between 200-400 nm and approximately 95-100% encapsulation efficiency were obtained. Release of shRNA changed with the molecular weight of chitosan. It was obtained that formulation containing shRNA plasmid targeting PDGF-D exon 6 (NP1) has the highest silencing efficiency in MDA-MB-231 cell line. It was also evaluated that chitosan can be a suitable gene delivery system for shRNA targeting PDGF-D.

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“…4,27,30,[73][74][75][76] To ensure the presence of trithiocarbonate or dithiobenzoate RAFT end-groups on the generated polymers, termination was minimized by selecting a low ratio of the polymerization initiator to the RAFT agent concentrations in the feed solutions (([Initiator] 0 / [RAFT] 0 ), i.e., 1/5 (theoretical functionality…”

Section: Raft Polymerizationmentioning

confidence: 99%

Modification of RAFT‐polymers via thiol‐ene reactions: A general route to functional polymers and new architectures

Boyer

Granville

Davis

et al. 2009

J. Polym. Sci. A Polym. Chem.

237

240

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An investigation into the aminolysis of x-end groups of RAFT-polymers and simultaneous thiol-ene reactions with ene-bearing compounds is described. Three different polymers, P(MMA), P(HPMA), and P(NIPAAm), with low PDIs were synthesized using dithiobenzoate and trithiocarbonate RAFT agents. P(NIPAAm) synthesized with trithiocarbonate RAFT agent and P(HPMA) synthesized with dithiobenzoate RAFT agent were both functionalized with a methacrylate-modified mannose and a maleimide-modified biotin via one-pot simultaneous aminolysis and thiol-ene reactions with product yields above 85%. The presence of ene-compounds during aminolysis was shown to prevent the formation of disulfide interchain crosslinking. Using the same approach, P(MMA), P(HPMA), and P(NIPAAm) were converted to (meth)acrylate macromonomers with high yields ([80%). In the case of P(MMA), the simultaneous aminolysis and thiol-ene addition prevented any intrachain side reactions, i.e., thiolactone formation. New architectures such as graft and block copolymers were successfully generated from the macromonomers.

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Corona-Stabilized Interpolyelectrolyte Complexes of SiRNA with Nonimmunogenic, Hydrophilic/Cationic Block Copolymers Prepared by Aqueous RAFT Polymerization

Cited by 85 publications

References 96 publications

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

In vitro gene silencing effect of chitosan/shRNA PDGF-D nanoparticles in breast cancer

Modification of RAFT‐polymers via thiol‐ene reactions: A general route to functional polymers and new architectures

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