Synthesis of Biocompatible PEG-Based Star Polymers with Cationic and Degradable Core for siRNA Delivery

被引：113

作者：

Cho, Hong Y. ^{[1
]}

Srinivasan, Abiraman ^{[2
]}

Hong, Joanna ^{[2
]}

Hsu, Eric ^{[2
]}

Liu, Shiguang ^{[2
]}

Shrivats, Arun ^{[2
]}

Kwak, Dan ^{[2
]}

Bohaty, Andrew K. ^{[1
]}

Paik, Hyun-jong ^{[3
]}

Hollinger, Jeffrey O. ^{[2
]}

Matyjaszewski, Krzysztof ^{[1
]}

机构：

[1] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA

[2] Carnegie Mellon Univ, Bone Tissue Engn Ctr, Pittsburgh, PA 15213 USA

[3] Pusan Natl Univ, Dept Polymer Sci & Engn, Pusan, South Korea

来源：

BIOMACROMOLECULES | 2011年 / 12卷 / 10期

基金：

美国国家科学基金会;

关键词：

TRANSFER RADICAL POLYMERIZATION; CROSS-LINKING MACROMONOMERS; TRANSFECTION EFFICIENCY; GENE-TRANSFER; COPOLYMER; CARRIERS; RNA; PROGRESS; BIODEGRADATION; NANOPARTICLES;

D O I：

10.1021/bm2006455

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical-copolymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2 (dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross-linker, SS) via an "arm-first" approach. The star polymers had a diameter similar to 15 nm and were degraded under redox conditions by glutathione treatment into individual polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by dynamic light scattering. The star polymers were cultured with mouse calvarial preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine biocompatibility. Data suggest-star polymers were biocompatible with >= 80% cell viability after 48 h of incubation even at high concentration (800 mu g/mL). Zeta potential values varied with N/P ratio confirming complexation with siRNA. Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed by confocal microscopy and flow cytometry after 24 h of incubation.

引用

页码：3478 / 3486

页数：9

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