Oligoproline-derived nanocarrier for dual stimuli-responsive gene delivery.
Oligoproline-derived nanocarrier for dual stimuli-responsive gene delivery.
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DOI：
10.1039/c5tb00988j
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发表时间：
2015-09-28
影响因子：
7
通讯作者：
Sung, Hak-Joon
中科院分区：
文献类型：
--
作者：
Gupta, Mukesh K.;Lee, Sue Hyun;Crowder, Spencer W.;Wang, Xintong;Hofmeister, Lucas H.;Nelson, Christopher E.;Bellan, Leon M.;Duvall, Craig L.;Sung, Hak-Joon
基因治疗是治疗血管疾病的一种有前景的方法；然而，成功的策略取决于开发安全有效的输送技术，并专门针对脉管系统的病变点。在动脉粥样硬化进展的关键阶段，血管平滑肌细胞（VSMC）会过量产生活性氧（ROS）。因此，在本研究中，ROS 被用作血管靶向基因传递的刺激物。采用生物共轭方法和受控反向加成断裂链转移 (RAFT) 聚合相结合，合成了一种新型 ROS 可裂解、pH 响应的 mPEG113-b-CP5K-b-PDMAEMA42-b-P(DMAEMA22-co-BMA40-co-PAA24) (PPDDBP) 聚合物，作为质粒 DNA (pDNA) 递送的纳米载体。 PPDDBP 聚合物的 ros 降解性通过 SIN-1 介导的 CP5K 肽接头裂解得到证实，GPC 色谱图发生 mPEG 肩峰出现和 zeta 电位 (ζ) 增加的变化。 Polyplex纳米载体还表现出有效的PDNA负载、血清稳定性和血液相容性，表明其在生理条件下具有优异的性能。该复合物表现出理想的内体逃逸 pH 响应性和有效的 ROS 响应性，可改善致病性 VSMC 体外模型中报告基因的摄取和表达的靶向性。这些数据表明，这种新型纳米载体复合物系统是一种有前途的基因递送工具，用于预防或治疗高 ROS 区域，例如动脉粥样硬化病变。
Gene therapy is a promising method for the treatment of vascular disease; however, successful strategies depend on the development of safe and effective delivery technologies with specific targeting to a diseased point of vasculature. Reactive oxygen species (ROS) are overproduced by vascular smooth muscle cells (VSMCs) at critical stages of atherosclerosis progression. Therefore, ROS were exploited as a stimulus for vascular targeted gene delivery in this study. A combination of bio-conjugation methods and controlled reverse addition-fragmentation chain-trasfer (RAFT) polymerization was utilized to synthesize a new ROS-cleavable, pH-responsive mPEG113-b-CP5K-b-PDMAEMA42-b-P(DMAEMA22-co-BMA40-co-PAA24) (PPDDBP) polymer as a nanocarrier for plasmid DNA (pDNA) delivery. The ros degradability of PPDDBP polymers was confirmed by SIN-1-mediated cleavage of CP5K peptide linkers through a shift in GPC chromatogram with an appearance of mPEG shoulder peak and an increase in zeta potential (ζ). The polyplex nanocarrier also demonstrated effective PDNA loading, serum stability, and hemocompatibility, indicating its excellent performance under physiological conditions. The polyplexes demonstrated ideal pH responsiveness for endosomal escape and effective ROS responsiveness for improved targeting in an in vitro model of pathogenic VSMCs in terms of both uptake and expression of reporter gene. These data suggest this novel nanocarrier polyplex system is a promising gene delivery tool for preventing or treating areas of high ROS, such as atherosclerotic lesions.
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影响因子：
14
作者：
Martin, John R.;Gupta, Mukesh K.;Page, Jonathan M.;Yu, Fang;Davidson, Jeffrey M.;Guelcher, Scott A.;Duvall, Craig L.
通讯作者：
Duvall, Craig L.
DOI：
10.1016/j.jconrel.2008.10.004
发表时间：
2009-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Convertine AJ;Benoit DS;Duvall CL;Hoffman AS;Stayton PS
通讯作者：
Stayton PS
DOI：
10.1039/c4tb01094a
发表时间：
2014-11-07
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Lee SH;Boire TC;Lee JB;Gupta MK;Zachman AL;Rath R;Sung HJ
通讯作者：
Sung HJ
DOI：
10.1016/j.jconrel.2012.07.042
发表时间：
2012-09-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Gupta MK;Meyer TA;Nelson CE;Duvall CL
通讯作者：
Duvall CL
影响因子：
5.5
作者：
Goloub, T;de Keizer, A;Stuart, MAC
通讯作者：
Stuart, MAC