Highly Branched Poly[dimethylaminoethyl methacrylate-co-bis(2-acryloyloxy) ethyl disulfide] for Efficient Intracellular Protein Delivery.

IF 5.2 Q1 POLYMER SCIENCE

ACS Macro Letters Pub Date : 2025-07-07 DOI:10.1021/acsmacrolett.5c00220

Xiaojia Wang,Wei Sun,Rui Guo,Zhili Li,Chenfei Wang,Zhedong Ma,Siyi Cai,Dezhong Zhou

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引用次数: 0

Abstract

Intracellular protein delivery holds great potential for the prevention and treatment of various diseases but remains challenging. Cationic polymers are promising candidates for protein delivery because of their highly tailorable chemical composition, topological structure, and terminal functionalities and thus are capable of navigating multiple extracellular and intracellular barriers. Here phenylboric acid (PBA)-functionalized, biodegradable, highly branched poly[dimethylaminoethyl methacrylate-co-bis(2-acryloyloxy) ethyl disulfide] [P(DM-co-DS)-E] were developed for efficient cytoplasmic protein delivery. The electrostatic interactions, nitrogen-boronate (N-B) coordination, and cation-π interactions between the DMAEMA units, PBA moieties, and protein facilitate protein packaging, leading to formation of nanosized, nearly neutral nanoparticles, while the disulfide bonds in the branching junctions impart biodegradability to promote protein release in the cytoplasm. In human chondrosarcoma (SW1353) cells, the optimal P(DM10-co-DS1)-E1 achieved up to 20-fold higher delivery efficiency compared to commercial PULSin, while maintaining high cell viability.

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高效细胞内蛋白质递送的高支化聚[二甲氨基乙基甲基丙烯酸酯-co-双（2-丙烯氧基）乙基二硫]。

细胞内蛋白递送在预防和治疗各种疾病方面具有巨大的潜力，但仍然具有挑战性。阳离子聚合物由于其高度可定制的化学成分、拓扑结构和末端功能，因此能够导航多种细胞外和细胞内屏障，是蛋白质递送的有希望的候选者。在这里，苯硼酸（PBA）功能化，可生物降解，高支化聚[二甲氨基乙基甲基丙烯酸酯-co-双（2-丙烯氧基）乙基二硫化物][P(DM-co-DS)-E]被开发用于高效的细胞质蛋白质递送。DMAEMA单元、PBA基团和蛋白质之间的静电相互作用、氮-硼酸盐（N-B）配位和阳离子-π相互作用促进了蛋白质的包装，形成了纳米级、接近中性的纳米颗粒，而分支连接中的二硫键赋予了生物可降解性，促进了蛋白质在细胞质中的释放。在人软骨肉瘤（SW1353）细胞中，最佳的P(DM10-co-DS1)-E1的递送效率比商业化的PULSin高20倍，同时保持了较高的细胞活力。

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来源期刊

ACS Macro Letters 化学-

CiteScore

10.40

自引率

3.40%

发文量

209

审稿时长

1 months

期刊介绍： ACS Macro Letters publishes research in all areas of contemporary soft matter science in which macromolecules play a key role, including nanotechnology, self-assembly, supramolecular chemistry, biomaterials, energy generation and storage, and renewable/sustainable materials. Submissions to ACS Macro Letters should justify clearly the rapid disclosure of the key elements of the study. The scope of the journal includes high-impact research of broad interest in all areas of polymer science and engineering, including cross-disciplinary research that interfaces with polymer science. With the launch of ACS Macro Letters, all Communications that were formerly published in Macromolecules and Biomacromolecules will be published as Letters in ACS Macro Letters.