Biodegradable Hyperbranched Poly(Amine-Co-Ester)-Based Polymeric Nanoparticles for mRNA Delivery

IF 19 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Functional Materials Pub Date : 2025-04-15 DOI:10.1002/adfm.202425986

Gan Liu, Wenqiang Xiang, Miaomiao Guan, Chuntao Xu, Jin Liu, Chao Zhao, Yang Deng

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Abstract

Despite the availability of mRNA vaccines utilizing lipid nanoparticles (LNPs) delivery technology, there remains a pressing need for the development of non-viral messenger ribonucleic acid (mRNA) delivery vectors that are both more efficient and safe. Here, a novel hyperbranched poly(amine-co-ester) (HBPA) system, catalyzed by immobilized lipase, is presented for efficient in vitro and in vivo mRNA delivery. By polymerizing four monomers - pentadecanolactone, sebacic acid, N-methyldiethanolamine, and triethanolamine-HBPA with a controllable hyperbranched structure is successfully synthesized. Subsequent end-group modification with amino compound E results in hyperbranched poly(amine-co-ester) with End group (HBPA-E). Comparative evaluations reveal that HBPA-E outperforms ≈7 times as linear poly(amine-co-ester) (LPA-E) and 3 times the commercial transfection reagent Lipofectamine MessengerMAX (LipoMM) in terms of intracellular delivery efficiency while demonstrating lower cytotoxicity. Furthermore, the in vivo pulmonary delivery efficiency of HBPA-E is 22 times that of LPA-E and the commercial in vivo delivery reagent in vivo-JetRNA, and intranasal delivery also exhibits high efficiency. Finally, the HBPA-E can be easily dissolved in ethanol, and its mRNA formulation can be employed as a freeze-drying formulation, making it a valuable candidate for future clinical applications of mRNA delivery.

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用于 mRNA 运送的可生物降解超支化聚（胺-共聚酯）聚合物纳米颗粒

尽管利用脂质纳米颗粒（LNPs）递送技术的mRNA疫苗是可用的，但仍然迫切需要开发更有效和安全的非病毒信使核糖核酸（mRNA）递送载体。本文提出了一种新型的超支化聚（胺-助酯）（HBPA）体系，由固定化脂肪酶催化，用于有效的体外和体内mRNA递送。通过对五酸内酯、癸二酸、n -甲基二乙醇胺和三乙醇胺四种单体的聚合，成功合成了具有可控超支化结构的hbpa。随后用氨基化合物E进行端基修饰，得到具有端基（HBPA-E）的超支化聚（胺-助酯）。比较评估显示，HBPA-E在细胞内传递效率方面优于线性聚胺-共酯（LPA-E）约7倍，是商业转染试剂Lipofectamine MessengerMAX （LipoMM）的3倍，同时显示出更低的细胞毒性。HBPA-E的肺内递送效率是LPA-E和商业体内递送试剂jetrna体内递送效率的22倍，鼻内递送效率也很高。最后，HBPA-E可以很容易地溶解在乙醇中，其mRNA制剂可以用作冷冻干燥制剂，使其成为未来mRNA递送临床应用的有价值的候选者。

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

Advanced Functional Materials 工程技术-材料科学：综合

CiteScore

29.50

自引率

4.20%

发文量

2086

审稿时长

2.1 months

期刊介绍： Firmly established as a top-tier materials science journal, Advanced Functional Materials reports breakthrough research in all aspects of materials science, including nanotechnology, chemistry, physics, and biology every week. Advanced Functional Materials is known for its rapid and fair peer review, quality content, and high impact, making it the first choice of the international materials science community.