Alshehry Yasir, Liu Xiang, Li Wenhua, Wang Qiyan, Cole Janét, Zhu Guizhi
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23298, United States of America.
Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, 31441, Dammam, Saudi Arabia.
AAPS J. 2025 Mar 18;27(3):66. doi: 10.1208/s12248-025-01051-8.
Cancer immunotherapy is poised to be one of the major modalities for cancer treatment. Messenger RNA (mRNA) has emerged as a versatile and promising platform for the development of effective cancer immunotherapy. Delivery systems for mRNA therapeutics are pivotal for their optimal therapeutic efficacy and minimal adverse side effects. Lipid nanoparticles (LNPs) have demonstrated a great success for mRNA delivery. Numerous LNPs have been designed and optimized to enhance mRNA stability, facilitate transfection, and ensure intracellular delivery for subsequent processing. Nevertheless, challenges remain to, for example, improve the efficiency of endosomal escape and passive targeting. This review highlights key advancements in the development of mRNA LNPs for cancer immunotherapy. We delve into the design of LNPs for mRNA delivery, encompassing the chemical structures, characterization, and structure-activity relationships (SAR) of LNP compositions. We discuss the key factors influencing the transfection efficiency, passive targeting, and tropism of mRNA-loaded LNPs. We also review the preclinical and clinical applications of mRNA LNPs in cancer immunotherapy. This review can enhance our understanding in the design and application of LNPs for mRNA delivery in cancer immunotherapy.
癌症免疫疗法有望成为癌症治疗的主要方式之一。信使核糖核酸(mRNA)已成为开发有效的癌症免疫疗法的一个通用且有前景的平台。mRNA疗法的递送系统对于其最佳治疗效果和最小副作用至关重要。脂质纳米颗粒(LNPs)已在mRNA递送方面取得了巨大成功。人们设计并优化了众多LNPs,以增强mRNA稳定性、促进转染并确保细胞内递送以便后续处理。然而,仍存在一些挑战,例如提高内体逃逸效率和被动靶向性。本综述重点介绍了用于癌症免疫疗法的mRNA-LNPs开发的关键进展。我们深入探讨了用于mRNA递送的LNPs的设计,包括LNP组合物的化学结构、表征以及构效关系(SAR)。我们讨论了影响载有mRNA的LNPs转染效率、被动靶向性和趋向性的关键因素。我们还综述了mRNA-LNPs在癌症免疫疗法中的临床前和临床应用。本综述可增进我们对用于癌症免疫疗法中mRNA递送的LNPs的设计和应用的理解。
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