Synthesis of Amphiphilic Cationic Poly(β-amino acid) Derivatives and Their PEG Length Optimization for mRNA Transfection.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2024-11-27 DOI:10.1021/acs.biomac.4c01265

Sung Been Lim, Jun Su An, DongHyun Kang, Ha Yeon Park, Mohit J Mehta, Eunyoung Choi, Beob Soo Kim, Hyun Jin Kim

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Abstract

We synthesized a series of amphiphilic cationic poly(ethylene glycol)-b-poly(β-amino acid) derivatives with various lengths of PEG to investigate the effects of PEG lengths on mRNA transfection. The surface charges of the polyplexes with a DP_OEG ≥ 4 gradually decreased as DP_OEG increased. This indicated that hydrophilic PEG with a DP_OEG ≥ 4 was exposed on the surface of the polyplexes, which was further confirmed using ¹H NMR. Polyplexes with a DP_OEG ≤ 4 exhibited mRNA transfection efficacy similar to that of homopolymers. However, the transfection efficacy of the polyplex with a DP_OEG ≥ 12 markedly decreased, mainly because of the decreased cellular uptake and stability of the polyplexes against serum albumin. This indicated that the PEG length considerably affected the delivery efficacy of IVT mRNA. Our results provide useful information for the fundamental polymer design to optimize the PEG length of amphiphilic cationic polymers for systemic IVT mRNA delivery.

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两亲性阳离子聚（β-氨基酸）衍生物的合成及其用于 mRNA 转染的 PEG 长度优化。

我们合成了一系列具有不同长度 PEG 的两亲性阳离子聚（乙二醇）-b-聚（β-氨基酸）衍生物，以研究 PEG 长度对 mRNA 转染的影响。随着 DPOEG 的增加，DPOEG ≥ 4 的多聚体的表面电荷逐渐减少。这表明 DPOEG ≥ 4 的亲水性 PEG 暴露在多聚体表面，1H NMR 进一步证实了这一点。DPOEG ≤ 4 的多聚物的 mRNA 转染效果与均聚物相似。然而，DPOEG ≥ 12 的多聚物的转染效果明显降低，这主要是因为多聚物的细胞吸收率和对血清白蛋白的稳定性降低了。这表明 PEG 长度在很大程度上影响了 IVT mRNA 的递送效果。我们的研究结果为聚合物的基础设计提供了有用的信息，有助于优化用于全身性 IVT mRNA 递送的两性阳离子聚合物的 PEG 长度。

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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.