Lipid Nanoparticles for mRNA Delivery in Cancer Immunotherapy.

IF 3.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY AAPS Journal Pub Date : 2025-03-18 DOI:10.1208/s12248-025-01051-8
Yasir Alshehry, Xiang Liu, Wenhua Li, Qiyan Wang, Janét Cole, Guizhi Zhu
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Abstract

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.

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用于肿瘤免疫治疗mRNA传递的脂质纳米颗粒。
癌症免疫疗法有望成为癌症治疗的主要方式之一。信使RNA (mRNA)已经成为开发有效的癌症免疫治疗的一个多功能和有前途的平台。mRNA治疗药物的递送系统对其最佳治疗效果和最小的不良副作用至关重要。脂质纳米颗粒(LNPs)在mRNA递送方面取得了巨大的成功。许多LNPs已经被设计和优化,以增强mRNA的稳定性,促进转染,并确保细胞内递送以进行后续处理。然而,挑战仍然存在,例如,提高内体逃逸和被动靶向的效率。本文综述了用于癌症免疫治疗的mRNA LNPs的主要进展。我们深入研究了用于mRNA递送的LNP的设计,包括LNP成分的化学结构、表征和构效关系(SAR)。我们讨论了影响mrna负载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在肿瘤免疫治疗中的临床前和临床应用。本文综述有助于加深我们对LNPs在肿瘤免疫治疗中mRNA传递的设计和应用的理解。
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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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