近年来，癌症免疫疗法已成为一种有前景的癌症治疗方法。纳米载体的物理和化学特性是调节肿瘤微环境（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-NP）的行为，重点关注它们与免疫细胞的相互作用以及它们从肿瘤到肿瘤引流淋巴结（tdLN）的转运机制。成功制备具有独特弹性特性的 Lipo-NPs，观察到它们在免疫细胞相互作用方面的不同行为。软脂质纳米粒子表现出对细胞膜的亲和力，而具有中等弹性的脂质纳米粒子则通过膜融合促进货物递送至巨噬细胞。相反，硬脂纳米颗粒通过经典的细胞摄取途径进入巨噬细胞。此外，值得注意的是，较软的 Lipo-NP 在体内表现出对 tdLN 的优异转运，这归因于其可变形性质和较低的弹性。结果，带有激动剂的中等弹性脂质纳米粒（cGAMP）通过激活STING途径并增强向tdLN的运输，促进肿瘤浸润淋巴细胞（TIL）的大量浸润，从而产生显着的抗肿瘤效果并延长黑色素瘤的生存期鼠标模型。此外，这项研究强调了中等弹性脂质纳米粒与免疫检查点阻断（ICB）疗法在防止肿瘤免疫逃避方面的潜在协同作用。这些发现有望指导癌症免疫治疗中的免疫靶向递送系统，特别是针对 tdLN 靶向和根除 tdLN 内转移的疫苗设计。

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.