Chimeric antigen receptor (CAR) therapy represents a promising modality for treating cancer and autoimmune diseases, employing genetically engineered immune cells. Despite remarkable clinical outcomes, its broad implementation is constrained by significant challenges, including toxicity, limited specificity, and complexities associated with genetic material delivery. Biological nanoparticles, such as exosomes, virus-like particles, and biomimetic nanostructures, possess unique properties that can address these limitations. These nanoplatforms enable targeted delivery of genetic constructs, mitigate the risk of cytokine release syndrome, modulate CAR cell activity, and can function as biosensors. Furthermore, they facilitate non-viral, in vivo CAR cell engineering, streamlining the process compared to conventional ex vivo methods. The advancement of in vivo strategies underscores the critical need to overcome toxicity hurdles inherent to current CAR-T platforms. In this context, exosomes and biomimetic nanoparticles offer considerable potential due to their innate biocompatibility, programmability, and versatile cargo capacity for payloads like mRNA and circular RNA. This review comprehensively outlines contemporary genetic platforms for CAR expression and examines the opportunities presented by biological delivery vehicles. It focuses on recent achievements and revisits fundamental CAR principles through the lens of emerging technologies aimed at confronting persistent challenges in the field.
嵌合抗原受体（CAR）疗法作为一种利用基因工程改造免疫细胞治疗癌症和自身免疫性疾病的新兴手段，展现出广阔前景。尽管临床疗效显著，但其广泛应用仍受限于毒性反应、靶向特异性不足及遗传物质递送复杂性等关键挑战。以外泌体、病毒样颗粒和仿生纳米结构为代表的生物纳米颗粒，凭借其独特性质为突破这些局限提供了可能。这类纳米平台能够实现遗传构建体的靶向递送，降低细胞因子释放综合征风险，调控CAR细胞活性，并可作为生物传感器使用。此外，它们促进了非病毒方式的体内CAR细胞工程化，较传统体外改造流程更为高效。体内策略的发展突显了克服当前CAR-T平台固有毒性问题的迫切需求。在此背景下，外泌体与仿生纳米颗粒因其天然生物相容性、可编程特性以及对mRNA、环状RNA等多种载荷的递送能力，展现出巨大潜力。本综述系统梳理了当前CAR表达的遗传学平台，深入探讨了生物递送载体带来的新机遇，聚焦该领域最新进展，并基于旨在解决长期挑战的新兴技术视角，重新审视了CAR疗法的基本原理。
CAR Therapies: Ex Vivo and In Vivo Potential of Exosomes and Biomimetic Nanoparticles
肿瘤(癌症)患者之家