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首页> 外文期刊>Biomaterials Science >Polymeric assembly of hyperbranched building blocks to establish tunable nanoplatforms for lysosome acidity-responsive gene/drug co-delivery
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Polymeric assembly of hyperbranched building blocks to establish tunable nanoplatforms for lysosome acidity-responsive gene/drug co-delivery

机译：高支链结构单元的聚合物组装，以建立可溶的纳米平台，用于溶酶体酸性反应性基因/药物共同递送

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This study plans to develop a nanoparticle technology that can assemble different polymeric "building blocks" with various desired functionalities into one nanosystem in a pH-dependent manner. For this purpose, polymeric building blocks were specifically designed with hyperbranched architectures, and orthogonal pH-reversible phenylboronic acid-diols were taken as "joints" to integrate them together. To verify the idea, a corona-core dual-polymer nanoassembly was prepared as the vehicle for lysosomotropic gene/drug co-delivery. Phenylboronic acid modified hyperbranched oligoethylenimine (OEI-PBA) was arranged to cluster around the hydrophobic core composed of hyperbranched polyglycerol, just by mixing two polymers in an appropriate ratio at neutral conditions. Compared with the parent OEI-PBA, this nanoassembly demonstrated better capture of plasmid DNA, highly enhanced activity for cellular transport and gene transfection (up to 100 fold), the ability to further load hydrophobic drugs, lysosome acidity-targeting pH-dependent release of both carried cargoes, and improved cell-biocompatibility. To evaluate its potential for combinational gene/drug therapy, in vitro experiments using the therapeutic p53 gene and antitumor doxorubicin as models were carried out. This intracellular co-delivery led to apparently synergetic anti-cancer effects in cultured cancer cells. This dynamic paradigm shows interesting features including easy manipulation, reversible conjugation, lysosome-targeting pH-responsiveness, high co-delivery efficiency, and functional expandability by further accommodating other building blocks.
机译：这项研究计划开发一种纳米粒子技术，该技术可以将各种具有各种所需功能的聚合物“构件”以pH依赖的方式组装到一个纳米系统中。为此，专门设计了具有超支链结构的聚合物构件，并将正交的pH可逆苯基硼酸-二醇作为“接头”将它们整合在一起。为了验证这一想法，准备了一个电晕核双聚合物纳米组件作为溶溶同质基因/药物共同递送的载体。只需在中性条件下以适当比例混合两种聚合物，即可将苯硼酸改性的超支化低聚亚乙基亚胺（OEI-PBA）聚集在由超支化聚甘油组成的疏水核周围。与亲本OEI-PBA相比，这种纳米组装体显示出更好的质粒DNA捕获，细胞转运和基因转染的活性大大增强（最高100倍），进一步装载疏水性药物的能力，靶向溶酶体酸度的pH依赖性释放。两者都携带货物，并改善了细胞的生物相容性。为了评估其联合基因/药物治疗的潜力，进行了以治疗性p53基因和抗肿瘤阿霉素为模型的体外实验。这种细胞内共同递送导致在培养的癌细胞中明显协同的抗癌作用。这种动态范式显示出有趣的功能，包括易于操作，可逆结合，靶向溶酶体的pH响应性，高共递送效率和通过进一步容纳其他结构单元的功能扩展性。

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