Augmenting stealth attributes and intracellular trafficking of polyplex micelles via charge-switching corona for superior gene transduction

文献类型： 外文期刊

第一作者： Tong, Changgui

作者： Tong, Changgui;Zhao, Yan;Chen, Qixian;Wang, Yue;Zhao, Yan;Wang, Yue;Zhao, Yan;Chen, Qixian;Wang, Yue;Lin, Sheng;Zhang, Yong;Lin, Sheng;Zhang, Yong;Chen, Qixian;Chen, Qixian;Chen, Qixian

作者机构：

关键词： pDNA; Nanomedicine; Dynamic surface chemistry; Charge reversal; Endolysosomes

期刊名称：CHINESE CHEMICAL LETTERS （ 影响因子：8.9； 五年影响因子：7.3 ）

ISSN： 1001-8417

年卷期： 2025 年 36 卷 10 期

页码：

收录情况： SCI

摘要： The surface physiochemical features of nanomedicine are essential for controlling biointerfacial interactions in biological compartments and achieving the programmed delivery scenario to intracellular targets. This work presents a novel dynamic triple-transformable surface engineering strategy that can adapt to sequential variable biological microenvironments and intelligently managing the previously acknowledged biological obstacles. By employing click chemistry, the surface of a classical PEGylated pDNA delivery nanoparticles were tethered with a multiple of charge-reversible polymers to endow the dynamic biointerfacial surroundings. Crucially, the dynamic surroundings had negative charge under physiological circumstances (pH 7.4), which inhibited structural disintegration brought on by charged biological species and anionic nuclease degradation. In addition, by regulating the first pass effect, the nanoparticles demonstrated appreciable stealth function that led to persistent systemic retention and improved bioavailability and consistent internalization into the targeted cells. In subsequence to cell endocytosis, translocation from the digestive endolysosomes to the targeted cytosol was facilitated due to acidification (endosomal pH 5.5) of the dynamic surroundings into highly positive charge, consequently leading to explosive disruptive effects on the endolysosomal structures and retrieve the bio-vulnerable pDNA payloads. In conclusion, our proposed unique dynamic surface chemistry provides a viable delivery mechanism that successfully navigates a series of biological roadblocks and collaborates to effectively express the encapsulated pDNA at the targeted cells. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

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