Iterative Screening of Vitamin E-Based Functional Lipid Nanoparticles for mRNA Delivery

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2025-05-28 DOI:10.1021/acsnano.5c01378

Kexin Cui, Zhang Fangming, Tianzi Shi, Siyu Zhao, Yixuan Zhou, Xiong Liu, Yong Hu, Zhaoyu Hu, Li Kong, Zhiping Zhang

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Abstract

Ionizable lipids are crucial for the effective delivery of mRNA by using lipid nanoparticles (LNPs). Endowing ionizable lipids with tailored biological properties could potentially augment the therapeutic efficacy of mRNA-based treatments. Herein, a functional vitamin E (VE)-based lipid library with distinct head groups was designed and synthesized. Due to the presence of VE, these lipids inherently exhibited immunomodulatory properties, including the promotion of cellular uptake, dendritic cells maturation, and antigen presentation. Through iterative optimization of the LNP components and the architecture of ionizable lipids, the correlation between the structure of ionizable lipids and their mRNA delivery efficiency has been established, leading to the finding of the most effective delivery formulation. Benefiting from the high mRNA delivery efficiency and the immunomodulatory function of LNPs themselves, VE-based LNPs have demonstrated complete remission in colon cancer by delivering mIL-12, which offered a beneficial combination with immune checkpoint blockade. The proposed functional LNPs were anticipated to furnish potential delivery systems for mRNA-based cancer treatments.

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用于mRNA递送的维生素基功能性脂质纳米颗粒的迭代筛选

可电离脂质对于使用脂质纳米颗粒（LNPs）有效递送mRNA至关重要。赋予可电离脂质定制的生物学特性可能潜在地增强基于mrna的治疗的治疗效果。本文设计并合成了一个具有不同头基的功能性维生素E脂质库。由于VE的存在，这些脂质固有地表现出免疫调节特性，包括促进细胞摄取、树突状细胞成熟和抗原呈递。通过对LNP组分和可电离脂质结构的迭代优化，建立了可电离脂质结构与其mRNA递送效率之间的相关性，从而找到了最有效的递送配方。得益于LNPs本身的高mRNA传递效率和免疫调节功能，基于ve的LNPs通过传递mIL-12在结肠癌中显示出完全缓解，mIL-12与免疫检查点阻断的有益组合。所提出的功能性LNPs有望为基于mrna的癌症治疗提供潜在的递送系统。

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

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.