Endo/Lysosomal-Escapable Lipid Nanoparticle Platforms for Enhancing mRNA Delivery in Cancer Therapy

被引：0

作者：

Wang, Jiapeng ^{[1
]}

Chen, Renjie ^{[2
]}

Xie, Yongyi ^{[2
]}

Qin, Xuanting ^{[2
]}

Zhou, You ^{[2
]}

Xu, Chuanshan ^{[2
]}

机构：

[1] Guangzhou Med Univ, Clin Coll 2, Dept Med Imageol, Guangzhou 511436, Peoples R China

[2] Guangzhou Med Univ, Sch Pharmaceut Sci, State Key Lab Resp Dis, Guangzhou 511436, Peoples R China

来源：

PHARMACEUTICS | 2025年 / 17卷 / 07期

关键词：

lipid nanoparticle; endo/lysosomal escape; mRNA delivery; gene therapy; ENDOSOMAL ESCAPE; INTRACELLULAR DELIVERY; MEDIATED ENDOCYTOSIS; CELLULAR UPTAKE; SIRNA DELIVERY; MEMBRANE; TRAFFICKING; MECHANISMS; TRANSPORT; EFFICACY;

D O I：

10.3390/pharmaceutics17070803

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

mRNA-based drug development is revolutionizing tumor therapies by enabling precise cancer immunotherapy, tumor suppressor gene restoration, and genome editing. However, the success of mRNA therapies hinges on efficient delivery systems that can protect mRNA from degradation and facilitate its release into the cytoplasm for translation. Despite the emergence of lipid nanoparticles (LNPs) as a clinically advanced platform for mRNA delivery, the efficiency of endo/lysosomal escape still represents a substantial bottleneck. Here, we summarize the intracellular fate of mRNA-loaded LNPs, focusing on their internalization pathways and processing within the endo-lysosomal system. We also discuss the impact of endo-lysosomal processes on mRNA delivery and explore potential strategies to improve mRNA escape from endo-lysosomal compartments. This review focuses on molecular engineering strategies to enhance LNP-mediated endo/lysosomal escape by optimizing lipid composition, including ionizable lipids, helper lipids, cholesterol, and PEGylated lipids. Additionally, ancillary enhancement strategies such as surface coating and shape management are discussed. By comprehensively integrating mechanistic insights into the journey of LNPs within the endo-lysosome system and recent advances in lipid chemistry, this review offers valuable inspiration for advancing mRNA-based cancer therapies by enabling robust protein expression.

引用

页数：28

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