School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, China.
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
ACS Appl Mater Interfaces. 2023 Sep 6;15(35):41817-41827. doi: 10.1021/acsami.3c06170. Epub 2023 Aug 25.
To achieve efficient gene delivery or , nonviral vectors should have excellent biostability across cellular and tissue barriers and also smart stimuli responsiveness toward controlled release of therapeutic genes into the cell nucleus. However, it remains a key challenge to effectively combine the biostability of covalent polymers with the stimuli responsiveness of noncovalent polymers into one nonviral vehicle. In this work, we report the construction of a kind of cationic supramolecular block copolymers (SBCs) through noncovalent polymerization of β-cyclodextrin/azobenzene-terminated pentaethylenehexamine (DMA-Azo-PEHA-β-CD) in aqueous media using β-CD-monosubstituted poly(ethylene glycol) (PEG-β-CD) as a supramolecular initiator. The resultant SBC exhibits superior biostability, biocompatibility, and light/pH dual-responsive characteristics, and it also demonstrates efficient plasmid DNA condensation capacity and the ability to rapidly release plasmid DNA into cells driven by visible light (450 nm). Eventually, this SBC-based delivery system demonstrates visible light-induced enhancement of gene delivery in both COS-7 and HeLa cells. We anticipate that this work provides a facile and robust strategy to enhance gene delivery or visible light-guided manipulation of genes, further achieving safe, highly efficient, targeting gene therapy for cancer.
为了实现高效的基因传递或转染，非病毒载体应该具有出色的跨细胞和组织屏障的生物稳定性，并且还应该对治疗基因向细胞核的控制释放具有智能的刺激响应性。然而，将共价聚合物的生物稳定性与非共价聚合物的刺激响应性有效地结合到一个非病毒载体中仍然是一个关键挑战。在这项工作中，我们报告了通过在水介质中非共价聚合β-环糊精/偶氮苯封端的五亚乙基六胺（DMA-Azo-PEHA-β-CD），使用β-CD-单取代聚（乙二醇）（PEG-β-CD）作为超分子引发剂来构建一种阳离子超分子嵌段共聚物（SBC）。所得的 SBC 表现出优异的生物稳定性、生物相容性和光/ pH 双重响应特性，并且还表现出高效的质粒 DNA 凝聚能力和在可见光（450nm）驱动下快速将质粒 DNA 释放到细胞中的能力。最终，基于这种 SBC 的递药系统在 COS-7 和 HeLa 细胞中表现出可见光诱导的基因转染增强。我们预计这项工作为增强基因传递或光引导基因操作提供了一种简单而强大的策略，进一步实现了安全、高效、靶向的癌症基因治疗。
