Positively Charged Dendron Micelles Display Negligible Cellular Interactions.

Positively Charged Dendron Micelles Display Negligible Cellular Interactions.
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DOI:
10.1021/mz300533w
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发表时间:
2013-01-15
期刊:
影响因子:
7.015
通讯作者:
Hong S
Hong S
中科院分区:
化学1区
文献类型:
--
作者:
Pearson RM;Patra N;Hsu HJ;Uddin S;Král P;Hong S

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合成了具有不同端基官能度(-NH 2、-COOH和-Ac)的PEG化树枝状基共聚物(PDC)并将其自组装成树枝状胶束,以研究末端表面电荷对胶束的尺寸、形态和细胞相互作用的影响.所有的树突胶束表现出相似的尺寸(20-60 nm)和球形形态,分别使用动态光散射和透射电子显微镜测量。使用共聚焦显微镜和流式细胞术评估树突状分子胶束的细胞相互作用。令人惊讶的是,虽然胺封端的树枝状聚合物是已知的强烈与细胞的非特异性相互作用,所有的表面改性的树枝状胶束表现出电荷不依赖的低水平的细胞相互作用。i)最小的端基效应,因为每种PDC与树枝状聚合物相比具有低约10倍的电荷数与分子量比;和ii)带正电荷的端基与聚乙烯之间的分子内和分子间氢键(乙二醇)(PEG)主链,这导致电荷的螯合,如原子分子动力学模拟所证明的。由于其粒径分布窄、形态均匀、非特异性细胞相互作用低,因此是一种很有前途的药物释放平台。
PEGylated dendron-based copolymers (PDC) with different end-group functionalities (-NH2, -COOH, and –Ac) were synthesized and self-assembled into dendron micelles to investigate the effect of terminal surface charges on size, morphology, and cellular interactions of the micelles. All of the dendron micelles exhibited similar sizes (20–60 nm) and spherical morphologies, as measured using dynamic light scattering and transmission electron microscopy, respectively. The cellular interactions of dendron micelles were evaluated using confocal microscopy and flow cytometry. Surprisingly, although amine-terminated dendrimers are known to strongly interact with cells non-specifically, all of the surface-modified dendron micelles exhibited charge-independent low-levels of cellular interaction. The unexpected results, particularly from the amine-terminated dendron micelles, could be attributed to: i) minimal end-group effects, as each PDC has an approximately 10-fold lower charge-number-to-molecular-weight ratio compared to the dendrimer; and ii) intra- and intermolecular hydrogen bonding between positively charged terminal groups with poly(ethylene glycol) (PEG) backbones, which leads to the sequestration of the charges, as demonstrated by atomistic molecular dynamics simulations. With the narrow size distribution, uniform morphologies, and low levels of non-specific cellular interactions, the dendron micelles offer a promising drug delivery platform.
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