Abstract：
Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.
摘要：
由于肿瘤内光热剂的积累不足以及治疗期间癌症免疫循环的逆转，光免疫疗法面临挑战。在这项研究中,一种抗PD-L1固定化磁性金纳米小屋，AuNH-2-Ab,光响应，热敏,和免疫调节特性，以有效抑制原发性肿瘤的生长，提高免疫原性细胞死亡（ICD）水平，逆转肿瘤免疫微环境（TIME），并因此抑制转移发展。AuNH-2-Ab在全身给药后实现高肿瘤积累（9.54％注射剂量），允许在肿瘤中调节超过50°C的热疗剂量。通过优化热疗剂量，AuNH-2-Ab同时靶向和消除癌细胞和肿瘤相关巨噬细胞，从而激活有效的抗肿瘤免疫力，而不会受到免疫抑制元件的损害。高温/pH诱导的AuNH-2-Ab的形态转化，涉及表面抗体的分离以抑制原位PD-L1，和内部岩藻依聚糖层的暴露，以激活自然杀伤（NK）细胞。这种精确的光免疫疗法重新编程时间，显著延长小鼠肝细胞癌模型（Hep55.1c）的生存期，并利用单一纳米平台利用ICD生产和检查点抑制剂的协同作用。
