Cheng Hung-Wei, Ou Yu-Ling, Kuo Chia-Chi, Tsao Hsin-Yi, Lu Huai-En
Department of Materials Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.
Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu 300193, Taiwan.
Polymers (Basel). 2021 Aug 15;13(16):2726. doi: 10.3390/polym13162726.
Immunotherapy is a newly developed method for cancer treatment, but still generates limited response in partial patients for hepatocellular carcinoma (HCC) because the immunity cycle is limited by the tumor microenvironment (TME). Herein, we introduce multifunctional gold nanocages (AuNCs)-based nanocarriers with Ansamitocin P3 (AP3) loaded and anti-PDL1 binding (AP3-AuNCs-anti-PDL1) which can combine photothermal therapy, chemotherapeutic agent-triggered DCs maturation, and checkpoint immunotherapy in one platform. The AP3-AuNCs-anti-PDL1 using Avidin-biotin to bind anti-PDL1 on the surface of AP3-AuNCs showed specifically cellular targeting compared to AuNCs, which can increase the immune responses. The AP3-AuNCs+NIR-10 min exhibited the highly activated DCs maturation with two-fold higher than control+NIR, which can be attributed to the significant release of AP3. The results illustrated the synergistic effect of tumor-associated antigens (TAAs) and controlled AP3 release under near infrared (NIR) in triggering effective DCs maturation. Among them, AP3 release played the more important role than the TAAs under PTT in promoting T-cell activation. These results illustrate the promising potential of AuNCs-based nanocarriers combined with AP3 and the checkpoint inhibitors to strengthen the positive loop of immunity cycle.
免疫疗法是一种新开发的癌症治疗方法，但对于肝细胞癌（HCC）患者仍仅产生有限的反应，因为免疫循环受肿瘤微环境（TME）限制。在此，我们引入了负载安丝菌素P3（AP3）并结合抗PDL1的基于多功能金纳米笼（AuNCs）的纳米载体（AP3-AuNCs-抗PDL1），其可在一个平台上结合光热疗法、化疗药物触发的树突状细胞（DCs）成熟和检查点免疫疗法。与AuNCs相比，利用抗生物素蛋白-生物素在AP3-AuNCs表面结合抗PDL1的AP3-AuNCs-抗PDL1表现出特异性细胞靶向性，可增强免疫反应。AP3-AuNCs+近红外（NIR）照射10分钟显示出高度活化的DCs成熟，比对照组+NIR高两倍，这可归因于AP3的大量释放。结果表明肿瘤相关抗原（TAAs）和近红外（NIR）下可控的AP3释放在触发有效的DCs成熟中具有协同作用。其中，在光热疗法（PTT）下，AP3释放在促进T细胞活化方面比TAAs发挥更重要的作用。这些结果表明基于AuNCs的纳米载体与AP3和检查点抑制剂相结合在加强免疫循环正反馈方面具有广阔的潜力。
