Rapid Cellular Internalization of Multifunctional Star Polymers Prepared by Atom Transfer Radical Polymerization

Rapid Cellular Internalization of Multifunctional Star Polymers Prepared by Atom Transfer Radical Polymerization
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DOI:
10.1021/bm1006272
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发表时间:
2010-09-01
期刊:
影响因子:
6.2
通讯作者:
Matyjaszewski, Krzysztof
Matyjaszewski, Krzysztof
中科院分区:
化学2区
文献类型:
--
作者:
Cho, Hong Y.;Gao, Haifeng;Matyjaszewski, Krzysztof

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采用原子转移自由基聚合(ATRP)方法,以聚乙二醇甲基醚甲基丙烯酸酯(PEGMA)、GRGDS改性聚乙二醇丙烯酸酯(GRGDS-PEGAcryl)、邻甲基丙烯酸荧光素(FMA)和乙二醇二甲基丙烯酸酯(EGDMA)为原料,通过原子转移自由基聚合(ATRP)方法合成了星形外围含有GRGDS(Gly-Arg-Gly-Asp-Ser)多肽序列的聚乙二醇型星形聚合物。通过动态光散射和原子力显微镜测量,星形聚合物的直径约为20 nm。荧光显微镜证实了FMA与恒星的偶联,H-1核磁共振光谱证实了GRGDS片段成功地附着在恒星的外围。将带有和不带有GRGDS外周多肽片段的荧光聚乙二醇星形聚合物与MC3T3-E1.4细胞共同培养。培养24小时后,这些星形聚合物的细胞存活率为90%,生物相容性良好。共聚焦显微镜观察MC3T3-E1.4细胞摄取聚乙二醇星状聚合物的情况。观察到GRGDS多肽对聚乙二醇星状聚合物的快速摄取(类似于流式细胞仪测量的15分钟内FITC阳性细胞的100%),这表明这些功能性星形聚合物的递送潜力增强。
Poly(ethylene glycol) (PEG) star polymers containing GRGDS (Gly-Arg-Gly-Asp-Ser) peptide sequences on the star periphery were synthesized by atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA), GRGDS modified poly(ethylene glycol) acrylate (GRGDS-PEG-Acryl), fluorescein o-methacrylate (FMA), and ethylene glycol dimethacrylate (EGDMA) via an "arm-first" method. Star polymers were approximately 20 nm in diameter, as measured by dynamic light scattering and atomic force microscopy. Conjugation of FMA to the stars was confirmed by fluorescence microscopy, and successful attachment of GRGDS segments to the star periphery was confirmed by H-1 NMR spectroscopy. Both fluorescent PEG star polymers with and without peripheral GRGDS peptide segments were cultured with MC3T3-E1.4 cells. These star polymers were biocompatible with >= 90% cell viability after 24 h of incubation. Cellular uptake of PEG star polymers in MC3T3-E1.4 cells was observed by confocal microscopy. Rapid uptake of PEG star polymers with GRGDS peptides (similar to 100% of FITC-positive cells in 15 min measured by flow cytometry) was observed, suggesting enhanced delivery potential of these functional star polymers.