共聚物
乙二醇
胶束
材料科学
膜
氟
聚合物
纳米颗粒
化学工程
乙醚
内化
渗透(战争)
共轭体系
药物输送
纳米技术
化学
高分子化学
有机化学
细胞
生物化学
水溶液
工程类
运筹学
作者
Cheng Zhang,Tianqing Liu,Wenqian Wang,Craig A. Bell,Yanxiao Han,Changkui Fu,Hui Peng,Xuecai Tan,Petr Král,Katharina Gaus,J. Justin Gooding,Andrew K. Whittaker
出处
期刊:ACS Nano
[American Chemical Society]
日期:2020-05-13
卷期号:14 (6): 7425-7434
被引量:31
标识
DOI:10.1021/acsnano.0c02954
摘要
Incorporation of fluorinated moieties in polymeric nanoparticles has been shown in many instances to increase their uptake by living cells and, hence, has proven to be a useful approach to enhancing delivery to cells. However, it remains unclear how incorporation of fluorine affects critical transport processes, such as interactions with membranes, intracellular transport, and tumor penetration. In this study, we investigate the influence of fluorine on transport properties using a series of rationally designed poly(oligo(ethylene glycol) methyl ether acrylate)-block-perfluoropolyether (poly(OEGA)m-PFPE) copolymers. Copolymers with different fluorine contents were prepared and exhibit aggregate in solution in a manner dependent on the fluorine content. Doxorubicin-conjugated poly(OEGA)20-PFPE nanoparticles with lower fluorine content exist in solution as unimers, leading to greater exposure of hydrophobic PFPE segments to the cell surface. This, in turn, results in greater cellular uptake, deeper tumor penetration, as well as enhanced therapeutic efficacy compared to that with the micelle-state nanoaggregates (poly(OEGA)10-PFPE and poly(OEGA)5-PFPE) with higher fluorine content but with less PFPE exposed to the cell membranes. Our results demonstrate that the aggregation behavior of these fluorinated polymers plays a critical role in internalization and transport in living cells and 3D spheroids, providing important design criteria for the preparation of highly effective delivery agents.
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