糖类材料在脂质纳米颗粒中的应用：从稳定保护到智能调控
Applications of Carbohydrate Materials in Lipid Nanoparticles: From Stabilization and Protection to Smart Regulation
洪旭怡 1曾小东 2苏吴越3
作者信息
- 1. 广西医科大学药学院，南宁 530000
- 2. 烟台新药创制山东省实验室，烟台 264117
- 3. 武汉大学药学院，武汉 430000
- 折叠
摘要
mRNA药物的临床应用高度依赖脂质纳米颗粒（LNP）递送系统，但现有LNP仍面临储存稳定性不足、肝脏被动富集明显以及PEG相关免疫原性等问题，限制了其在常温储运、肝外靶向和重复给药中的进一步应用。近年来，糖类材料凭借优异的亲水性、生物相容性、结构多样性及受体识别能力，逐渐成为LNP功能化改造的重要方向。一方面，糖分子可通过玻璃化作用和氢键替代效应提高LNP及mRNA在制备、冻干和储存过程中的稳定性；另一方面，糖基修饰可借助糖-受体特异性识别实现对树突状细胞、巨噬细胞及特定器官的主动靶向递送。部分糖脂和多糖还兼具免疫调节活性，能够增强抗原递呈、改善细胞内微环境并提升mRNA疫苗的免疫效力。更重要的是，糖基材料有望替代PEG构建新型PEG-free LNP体系，在维持递送性能的同时降低抗PEG抗体介导的加速清除风险。本文围绕稳定保护、主动靶向、免疫增强和PEG替代四个方面，综述糖类材料在mRNA-LNP体系中的研究进展，并对其临床转化前景进行展望。
Abstract
The clinical impact of mRNA therapeutics depends heavily on lipid nanoparticle (LNP) delivery systems. Despite their central role in mRNA vaccines and nucleic acid medicines, current LNPs remain limited by insufficient storage stability, pronounced hepatic tropism and PEG-associated immunogenicity, which constrain their broader use in ambient storage, extrahepatic delivery and repeated administration. In this context, carbohydrate-based materials have emerged as versatile tools for LNP engineering because of their hydrophilicity, biocompatibility, structural diversity and receptor-recognition properties. Beyond serving as excipients, carbohydrates can stabilize LNPs and protect mRNA during formulation, lyophilization and storage through vitrification and hydrogen-bond substitution. Glycan-mediated recognition can also support active delivery to dendritic cells, macrophages and selected tissues. In addition, certain glycolipids and polysaccharides possess intrinsic immunomodulatory activity, enhancing antigen presentation, improving the intracellular environment and strengthening vaccine-induced immune responses. Carbohydrate-derived materials are also being explored as PEG substitutes for the development of PEG-free LNPs, with the potential to maintain delivery efficiency while reducing anti-PEG antibody-mediated accelerated clearance. This Review summarizes recent advances in carbohydrate-based materials for mRNA-LNP systems, focusing on stability protection, active targeting, immune potentiation and PEG replacement, and discusses their translational prospects.关键词
糖类材料、脂质纳米颗粒、mRNA递送、主动靶向、PEG替代、免疫调节Key words
carbohydrate-based materials/lipid nanoparticles/mRNA delivery/active targeting/PEG substitution/immunomodulation引用本文复制引用
洪旭怡,曾小东,苏吴越.糖类材料在脂质纳米颗粒中的应用：从稳定保护到智能调控[EB/OL].(2026-04-14)[2026-04-15].http://www.paper.edu.cn/releasepaper/content/202604-124.学科分类
生物科学研究方法、生物科学研究技术/生物化学/分子生物学/生物工程学
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