Long‐Term Storage Stable Vesicle‐Like Nanoparticles of Lipid and Polymer for siRNA and mRNA‐Mediated Cancer Immunotherapy

• Published in: Advanced functional materials Vol. 34; no. 44
• Main Authors: Chen, Chaoran, Zhang, Yuxi, Cao, Ziyang, Li, Dongdong, Zhu, Yueqiang, Jing, Houjin, Li, Yan, Li, Fangzheng, Xu, Cong‐Fei, Yang, Xianzhu, Wang, Jun
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.10.2024
• Subjects: Antigens; Cancer; cancer immunotherapy; Cationic polymerization; Efficiency; Genes; Immunotherapy; lipid/polymer nanoparticle; Lipids; Lymphocytes; mRNA vaccine; Nanoparticles; Polymers; Ribonucleic acid; RNA; RNA delivery; Shelf life; Vaccines; vesicle‐like nanoparticle
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202406101

RNA‐based therapeutics have emerged as a promising strategy for cancer immunotherapy, encompassing the silencing of immune checkpoint genes, chimeric antigen receptor T (CAR‐T) cell production, and antitumor vaccines. Despite their tremendous potential, the urgent need for the development of clinically applicable delivery systems remains paramount. In this study, vesicle‐like nanoparticles (VNPs) are devised using clinically approved amphiphilic polymers and lipids as the delivery system for siRNA and mRNA. Through meticulous formulation adjustments of cationic lipids and ionizable lipids, a VNP formulation with exceptional transfection efficiency is identified. Notably, the VNPs maintained their remarkable transfection efficiency even after 6 months of storage. When loaded with siPD‐L1 and siCD47, these VNPs effectively silenced two critical immune checkpoint genes, enabling successful cancer immunotherapy. Moreover, when employed as a delivery system for mRNA vaccines, the VNPs induced a robust population of antigen‐specific CD8+ T cells in immunized mice. This led to the successful suppression of tumor growth (5 out of 8 subjects becoming tumor‐free) and nearly complete inhibition of lung metastasis. In summary, this lipid‐ and polymer‐based VNPs offer a long shelf life, excellent loading and transfection efficiency, versatility for various RNA types, and hold great promise as a delivery system for clinical applications. This study presents the development of a vesicle‐like polymer nanoparticle (VNP) using clinically approved polymers and lipids as a stable carrier for nucleic acid delivery. The VNP demonstrates a prolonged shelf life, high loading and transfection efficiency, adaptability for different types of RNA, and effective delivery of siRNA and mRNA to boost the immune response against tumor growth.