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生物还原性阳离子聚合物与金纳米粒子的络合作用提高了血清中的稳定性及其在非病毒基因传递中的应用。

Complexation of bioreducible cationic polymers with gold nanoparticles for improving stability in serum and application on nonviral gene delivery.

机构信息

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.

出版信息

ACS Appl Mater Interfaces. 2015 Apr 15;7(14):7724-31. doi: 10.1021/acsami.5b00732. Epub 2015 Mar 20.

DOI:10.1021/acsami.5b00732
PMID:25764067
Abstract

Widespread applications of conventional polymeric gene carriers are greatly hampered by their inefficient transfection performance under serum-containing environment. Aiming to overcome this limitation, we propose a bioreducible polyethylenimine-gold nanocomplex system (SSPEI-Au NC), which can be prepared by a simple layer-by-layer (LBL) assembly procedure. SSPEI-Au NC contains sequentially deposited layers of bioreducible polyethylenimine (SSPEI) and poly(γ-glutamic acid) (γ-PGA) for efficient binding and delivery of plasmid DNA (pDNA). SSPEI-Au NC was characterized for various physicochemical properties, including: UV-vis spectra, TEM imaging, hydrodynamic size, and pDNA binding ability. The SSPEI-Au NC were efficiently uptaken by mammalian cells as observed using dark-field microscopy. Comparing to nondegradable PEI25k, the bioreducible SSPEI-Au NC exhibited superior transfection capability under serum-containing condition while causing lower cytotoxicity on mammalian cell lines. The effect of serum on SSPEI-Au NC dispersity was studied using UV-vis spectrometry and the results suggest that serum-assisted colloidal stability of SSPEI-Au NC contributed to its serum-resistant transfection.

摘要

传统聚合物基因载体的广泛应用受到其在含血清环境中低效转染性能的极大阻碍。为了克服这一限制,我们提出了一种生物还原型聚乙烯亚胺-金纳米复合物系统(SSPEI-AuNC),可以通过简单的层层(LBL)组装程序制备。SSPEI-AuNC 包含生物还原型聚乙烯亚胺(SSPEI)和聚(γ-谷氨酸)(γ-PGA)的顺序沉积层,用于有效结合和递送电性质粒 DNA(pDNA)。对 SSPEI-AuNC 进行了各种物理化学性质的表征,包括:紫外可见光谱、TEM 成像、水动力尺寸和 pDNA 结合能力。用暗场显微镜观察到 SSPEI-AuNC 被哺乳动物细胞有效摄取。与不可降解的 PEI25k 相比,在含血清条件下,生物还原型 SSPEI-AuNC 表现出优越的转染能力,同时对哺乳动物细胞系的细胞毒性较低。使用紫外可见光谱研究了血清对 SSPEI-AuNC 分散性的影响,结果表明血清辅助的 SSPEI-AuNC 胶体稳定性有助于其抗血清转染。

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