Thermoresponsive cationic dendronized copolymers and their corresponding nanogels as smart gene carriers
Thermoresponsive cationic dendronized copolymers and their corresponding nanogels as smart gene carriers
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DOI：
10.1039/d0py00631a
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发表时间：
2020-07-07
影响因子：
4.6
通讯作者：
Zhang, Afang
中科院分区：
文献类型：
--
作者：
Wu, Di;Wu, Jianhui;Zhang, Afang
聚合物的树枝化增强了拥挤效应和协同效应，从而有效地包裹和保护生物大分子，这可能为开发新型先进生物材料提供新的策略。本文制备了一类温度响应性树枝状共聚物及其纳米凝胶，并对其作为siRNA载体的性能进行了研究。这些共聚物材料由乙氧基和氨基封端的树枝状低聚乙二醇（OEG）部分构成，以分别提供与siRNA特异性相互作用的热响应性和正电荷。来自树枝状结构的多价性为这些阳离子共聚物材料提供了用于与带负电荷的siRNA有效缩合的适当组合物，并为它们提供了优异的保护。OEG树枝状分子的温敏特性可以通过在生理温度下相变时共聚物链的坍塌有利地触发封装的siRNA的释放。与共聚物相比，相应的纳米凝胶显示出有利的倾向，即使当存在少量的铵单元时，也能冷凝、保护和有效地释放siRNA。在纳米凝胶的球形形态中，分子间附加的树枝状基元的邻近效应显著增强。纳米凝胶/siRNA复合物可以被细胞有效地吸收，并极大地敲低靶基因的表达。这些特征保证了树枝化的基于共聚物的纳米凝胶作为非常有前途的基因递送载体。
Dendronization of polymers enhances the crowding and cooperative effects to provide efficient encapsulation and protection of biomacromolecules, which may provide a new strategy for developing novel advanced biomaterials. In the present work, a class of thermoresponsive dendronized copolymers and their corresponding nanogels were prepared, and their properties as siRNA carriers were investigated. These copolymer materials are constituted with ethoxyl- and amino-terminated dendritic oligoethylene glycol (OEG) moieties to provide thermoresponsiveness and positive charges for specific interaction with siRNA, respectively. Multivalency from the dendritic architecture affords these cationic copolymer materials appropriate compositions for efficient condensation with negatively charged siRNAs, and provides excellent protection for them. Thermoresponsive properties from the OEG dendrons can favorably trigger the release of encapsulated siRNAs through the collapse of copolymer chains upon phase transitions at physiological temperature. In comparison with the copolymers, the corresponding nanogels show favorable propensity to condensate, protect, and efficiently release siRNAs even when a low amount of ammonium units was presented. The enhanced proximity effects from intermolecularly appended dendrons within the spherical morphology of nanogels are remarkable. The nanogels/siRNA complex can be taken up efficiently by the cells, and greatly knock down the expression of target genes. These features guarantee dendronized copolymer-based nanogels as highly promising vectors for gene delivery.