Multifunctional and UV Light-Triggered Degradable Highly Branched Vinyl Polymer for Efficient mRNA Delivery.

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-10-14 DOI:10.1021/acs.biomac.5c00555

Wei Sun, Xiaojia Wang, Chenfei Wang, Zhili Li, Rui Guo, Zhedong Ma, Li Luo, Ming Zeng, Dezhong Zhou

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引用次数: 0

Abstract

Vinyl polymers synthesized via radical polymerization of (meth)acrylates are widely used in various biomedical fields. We developed a multifunctional, highly branched vinyl polymer, HPNDN, with ultraviolet (UV) light-triggered degradability for highly efficient mRNA delivery. (2-Nitro-1,3-phenylene) bis(methylene) diacrylate (NPBMDA) was copolymerized with 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 3,3,4,4,5,5,6,6-nonafluorohexyl acrylate (NFHA) by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by end-capping with ethylenediamine (EDA), resulting in HPNDN with a highly branched topological structure, multiple fluorine moieties, and multiple amines. Upon exposure to UV light irradiation, HPNDN degrades within 5 min through the cleavage of the ester groups in the NPBMDA units. Importantly, HPNDN can effectively condense mRNA to form nanosized polyplexes, achieving high transfection efficiency of up to 87.99%, 62.75% and 52.37% in African green monkey kidney (COS-7) cells, human embryonic kidney (293T) cells, and rat schwann (RSC96) cells, respectively, without inducing obvious cytotoxicity.

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多功能和紫外光触发的可降解高支化乙烯基聚合物用于mRNA的高效传递。

甲基丙烯酸酯自由基聚合合成的乙烯基聚合物广泛应用于各种生物医学领域。我们开发了一种多功能，高支化的乙烯基聚合物，HPNDN，具有紫外线（UV）触发的可降解性，用于高效的mRNA传递。通过可逆加成-断裂链转移（RAFT）聚合，将（2-硝基-1,3-苯基）双（亚甲基）二丙烯酸酯（NPBMDA）与2-（二甲氨基）甲基丙烯酸乙酯（DMAEMA）和3,3,4,4,5,5,6,6-非氟己基丙烯酸酯（NFHA）共聚，并与乙二胺（EDA）端盖，得到具有高支链拓扑结构、多氟基团和多胺的HPNDN。在紫外线照射下，HPNDN在5分钟内通过NPBMDA单元中的酯基裂解降解。重要的是，HPNDN可以有效地将mRNA凝聚形成纳米级多聚体，在非洲绿猴肾（cs -7）细胞、人胚胎肾（293T）细胞和大鼠雪旺氏（RSC96）细胞中的转染效率分别高达87.99%、62.75%和52.37%，且不产生明显的细胞毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.