Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
ACS Nano. 2024 Aug 27;18(34):23797-23811. doi: 10.1021/acsnano.4c09094. Epub 2024 Aug 14.
Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.
近年来，癌症免疫疗法已成为癌症治疗的一种有前途的方法。纳米载体的物理和化学性质是调节肿瘤微环境（TME）中抗原呈递细胞（APC）免疫激活的关键因素。在此，我们广泛研究了具有不同弹性的脂质体纳米颗粒（Lipo-NPs）的行为，重点研究了它们与免疫细胞的相互作用及其从肿瘤到肿瘤引流淋巴结（tdLNs）的转运机制。成功制备了具有不同弹性特性的 Lipo-NPs，观察到它们在与免疫细胞相互作用方面的行为存在差异。软 Lipo-NPs 对细胞膜具有亲和力，而具有中等弹性的 Lipo-NPs 通过膜融合促进货物向巨噬细胞的递送。相反，硬 Lipo-NPs 通过经典的细胞内摄取途径进入巨噬细胞。此外，值得注意的是，在体内，更柔软的 Lipo-NPs 具有更好的向 tdLNs 的转运能力，这归因于其具有较低弹性的可变形特性。结果，具有激动剂（cGAMP）的中等弹性 Lipo-NPs 通过激活 STING 途径并增强向 tdLNs 的转运，促进了肿瘤浸润淋巴细胞（TILs）的大量浸润，在黑色素瘤小鼠模型中产生了显著的抗肿瘤作用和延长的生存时间。此外，本研究强调了中等弹性 Lipo-NPs 与免疫检查点阻断（ICB）治疗联合使用在防止肿瘤免疫逃逸方面的潜在协同作用。这些发现为癌症免疫治疗中的免疫靶向递药系统提供了指导，特别是在针对 tdLNs 的疫苗设计和消除 tdLNs 内转移方面。
