Zhao Zengkai, Li Mingmei, Zheng Xiang, Gao Pengli, Huang Chenlu, Yu Qingyu, Jin Limin, Zhang Linhua, Zhu Dunwan, Li Fangzhou
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, People's Republic of China.
Nanotechnology. 2025 May 16;36(22). doi: 10.1088/1361-6528/add482.
Chimeric antigen receptor T cells (CAR-T) immunotherapy has achieved remarkable progress in the treatment of hematological malignancies. However, it encounters challenges including complex manufacturing processes, high cost, and safety issues. Lipid nanoparticle (LNP) technology, as an advanced gene delivery platform, offers significant advancements to CAR-T therapy through its high efficiency, low immunogenicity, and safety. LNP enableproduction of CAR-T cells, thereby improving delivery efficiency, reducing the risks of immunogenicity and insertional mutations, simplifying the production process and reducing costs. The scalability and rapid optimization ability of LNP position them as promising candidates for CAR-T cell production. LNP technology is expected to further promote the development of CAR-T immunotherapy and provide safer and more economical treatment options. Therefore, this paper aims to provide a comprehensive and systematic review of the application of LNP in CAR-T therapy. In this review, we initially outline the fundamental design, process, and current challenges of CAR-T therapy. Subsequently, we present the characteristics of LNP, their advantages as a gene delivery vectors, and how they improve the efficacy of CAR-T therapy. Finally, we summarize the current research landscape of LNP applications in CAR-T therapy. This includes enhancingtransfection of T cells, programming T cells, facilitating T-cell activation, alleviating the side effects of CAR-T therapy, and combining CAR-T therapy with other immunotherapies. These advancements will aid in the design of mRNA delivery systems based on LNP, thereby promoting the development of CAR-T therapy.
嵌合抗原受体T细胞（CAR-T）免疫疗法在血液系统恶性肿瘤的治疗中取得了显著进展。然而，它面临着包括复杂的生产工艺、高成本和安全问题等挑战。脂质纳米颗粒（LNP）技术作为一种先进的基因递送平台，凭借其高效性、低免疫原性和安全性，为CAR-T疗法带来了重大进展。LNP能够生产CAR-T细胞，从而提高递送效率，降低免疫原性和插入突变的风险，简化生产过程并降低成本。LNP的可扩展性和快速优化能力使其成为CAR-T细胞生产的有前景的候选者。LNP技术有望进一步推动CAR-T免疫疗法的发展，并提供更安全、更经济的治疗选择。因此，本文旨在对LNP在CAR-T疗法中的应用进行全面系统的综述。在本综述中，我们首先概述了CAR-T疗法的基本设计、过程和当前面临的挑战。随后，我们介绍了LNP的特性、它们作为基因递送载体的优势，以及它们如何提高CAR-T疗法的疗效。最后，我们总结了LNP在CAR-T疗法中应用的当前研究概况。这包括增强T细胞转染、对T细胞进行编程、促进T细胞活化、减轻CAR-T疗法的副作用，以及将CAR-T疗法与其他免疫疗法相结合。这些进展将有助于基于LNP的mRNA递送系统的设计，从而推动CAR-T疗法的发展。
