以mRNA-脂质纳米粒子为靶向治疗癌症:关键考虑因素和未来展望。
Targeting cancer with mRNA-lipid nanoparticles: key considerations and future prospects.
发表日期:2023 Aug 16
作者:
Edo Kon, Nitay Ad-El, Inbal Hazan-Halevy, Lior Stotsky-Oterin, Dan Peer
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
利用mRNA-脂质纳米颗粒(LNPs)治疗癌症患者是一个持续的研究领域,早在这些多功能纳米颗粒成功应用于COVID-19疫苗之前就已经开始。目前,正在进行利用这种平台用于癌症治疗的努力,主要集中在靶向多个新抗原的癌症疫苗或编码促炎细胞因子的mRNA-LNPs的直接肿瘤内注射。在本综述中,我们描述了在肿瘤治疗中使用mRNA-LNPs的机会,并讨论了将这些纳米颗粒的临床前研究发现成功转化为临床应用的挑战。我们对各种mRNA-LNP靶向和传递策略的潜力进行了批判性评估,考虑到生理学、技术和制造方面的挑战。我们探讨了这些方法在特定临床应用中最适合的潜在应用,并强调目前需要解决的障碍。最后,我们提供了从临床前和临床研究中得出的见解,这些研究正在使这种强大的平台被认为是肿瘤治疗的下一个前沿。 © 2023. Springer Nature Limited.
Harnessing mRNA-lipid nanoparticles (LNPs) to treat patients with cancer has been an ongoing research area that started before these versatile nanoparticles were successfully used as COVID-19 vaccines. Currently, efforts are underway to harness this platform for oncology therapeutics, mainly focusing on cancer vaccines targeting multiple neoantigens or direct intratumoural injections of mRNA-LNPs encoding pro-inflammatory cytokines. In this Review, we describe the opportunities of using mRNA-LNPs in oncology applications and discuss the challenges for successfully translating the findings of preclinical studies of these nanoparticles into the clinic. We critically appraise the potential of various mRNA-LNP targeting and delivery strategies, considering physiological, technological and manufacturing challenges. We explore these approaches in the context of the potential clinical applications best suited to each approach and highlight the obstacles that currently need to be addressed to achieve these applications. Finally, we provide insights from preclinical and clinical studies that are leading to this powerful platform being considered the next frontier in oncology treatment.© 2023. Springer Nature Limited.