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脂质纳米颗粒介导的mRNA递送在癌症免疫治疗中的应用

Lipid nanoparticle mediated mRNA delivery in cancer immunotherapy.

作者信息

Asthana Gyati Shilakari, Bhattacharjee Saptarshee, Kumar Jitendra, Sayyed Soyal, Jindal Amulya, Kumar Pankaj, Chinchane Abhijeet, Bhattacharyya Atreyee, Jaiswal Roshani, Kulkarni Sagar, Gajdhane Shubham, Madan Jitender, Asthana Abhay

机构信息

Gokaraju Rangaraju College of Pharmacy, Hyderabad, Telangana, India.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.

出版信息

Adv Immunol. 2025;166:37-75. doi: 10.1016/bs.ai.2025.02.001. Epub 2025 Mar 5.

Abstract

Lipid nanoparticles (LNPs) to deliver messenger RNA (mRNA) have emerged as a transformative strategy in cancer immunotherapy. This chapter explores the pivotal role of LNPs in enabling the efficient and targeted delivery of mRNA for cancer treatment, offering an innovative alternative to traditional therapies. LNPs protect mRNA from degradation, ensure its safe passage into the cytoplasm of target cells, and promote the expression of tumor-specific antigens that can activate the immune system against cancer cells. This chapter covers the fundamental properties of lipid nanoparticles, including their composition, structure, and functional modifications, as well as their mechanism of action in mRNA delivery. It also delves into optimizing LNPs to enhance targeting specificity, reduce toxicity, and improve therapeutic efficacy in cancer immunotherapy. Advances in the design of these nanoparticles, including innovations in surface functionalization and their role in overcoming tumor microenvironment barriers, are discussed. The chapter further examines preclinical and clinical applications of LNP-mediated mRNA cancer vaccines and therapies, highlighting recent successes and case studies. In addition, challenges such as ensuring efficient delivery, managing off-target effects, and addressing potential immune reactions are explored. Finally, future perspectives on developing more advanced LNPs and mRNA therapies, including their potential for personalized cancer treatments, are discussed. By providing an in-depth understanding of the current state and future potential of LNP-mediated mRNA delivery, this chapter aims to offer valuable insights into how this technology is shaping the future of cancer immunotherapy.

摘要

用于递送信使核糖核酸(mRNA)的脂质纳米颗粒(LNPs)已成为癌症免疫治疗中的一种变革性策略。本章探讨了脂质纳米颗粒在实现mRNA高效靶向递送以用于癌症治疗方面的关键作用,为传统疗法提供了一种创新的替代方案。脂质纳米颗粒可保护mRNA不被降解,确保其安全进入靶细胞的细胞质,并促进肿瘤特异性抗原的表达,从而激活免疫系统对抗癌细胞。本章涵盖了脂质纳米颗粒的基本特性,包括其组成、结构和功能修饰,以及它们在mRNA递送中的作用机制。它还深入探讨了优化脂质纳米颗粒以提高靶向特异性、降低毒性并改善癌症免疫治疗中的疗效。讨论了这些纳米颗粒设计方面的进展,包括表面功能化的创新及其在克服肿瘤微环境障碍中的作用。本章进一步研究了脂质纳米颗粒介导的mRNA癌症疫苗和疗法的临床前和临床应用,突出了近期的成功案例和研究。此外,还探讨了诸如确保有效递送、管理脱靶效应以及应对潜在免疫反应等挑战。最后,讨论了开发更先进的脂质纳米颗粒和mRNA疗法的未来前景,包括它们在个性化癌症治疗中的潜力。通过深入了解脂质纳米颗粒介导的mRNA递送的当前状态和未来潜力,本章旨在为这项技术如何塑造癌症免疫治疗的未来提供有价值的见解。

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