Huang Xingyue, Tian Xuehao, Zhang Qing, Hu Haiyan, Gao Jiahui, Ma Baonan, Wu Kai, Bai Jie, Du Shouying, Lu Yang, Han Ning
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Biomater Sci. 2021 Sep 14;9(18):6282-6294. doi: 10.1039/d1bm00474c.
Photothermal therapy (PTT) is able to ablate tumors hyperthermia, while immunotherapy could prevent tumor recurrence and metastasis by activating the host immune responses. Therefore, the combination of PTT and immunotherapy offers great advantages for the treatment of cancer. To achieve this goal, poly tannic acid (pTA) coated PLGA nanoparticles (PLGA-pTA NPs) were synthesized for combined photothermal-immunotherapy. pTA was a coordination complex formed by TA and Fe and it could be easily coated on PLGA NPs within seconds with a coating rate of 5.89%. As a photothermal agent, PLGA-pTA revealed high photothermal conversion efficiency and excellent photo-stability upon 808 nm laser irradiation. It also exhibited strong photothermal cytotoxicity against 4T1 cells. Moreover, PLGA-pTA based PTT could effectively trigger DC maturation since it could induce the release of DAMPs. The result of animal experiments showed that PLGA-pTA plus laser irradiation raised the tumor temperature up to 60 °C and effectively suppressed the growth of primary tumors. What's more, the progression of distant tumors as well as lung metastasis was also significantly inhibited due to the activation of anti-tumor responses by PLGA-pTA mediated PTT. When further combined with anti-PD-L1 antibody (a-PD-L1), the tumor growth and metastasis were almost completely inhibited. Our study provided a versatile platform to achieve combined photothermal-immunotherapy with enhanced therapeutic efficacy.
光热疗法（PTT）能够通过热疗消融肿瘤，而免疫疗法可通过激活宿主免疫反应来预防肿瘤复发和转移。因此，PTT与免疫疗法的联合应用为癌症治疗带来了巨大优势。为实现这一目标，合成了聚单宁酸（pTA）包覆的聚乳酸-羟基乙酸共聚物纳米颗粒（PLGA-pTA NPs）用于光热免疫联合治疗。pTA是由TA和Fe形成的配位络合物，它能在数秒内轻松包覆在PLGA NPs上，包覆率为5.89%。作为一种光热剂，PLGA-pTA在808 nm激光照射下显示出高光热转换效率和出色的光稳定性。它对4T1细胞也表现出强烈的光热细胞毒性。此外，基于PLGA-pTA的PTT能够有效触发树突状细胞（DC）成熟，因为它能诱导损伤相关分子模式（DAMPs）的释放。动物实验结果表明，PLGA-pTA加激光照射可将肿瘤温度升高至60°C，并有效抑制原发性肿瘤的生长。更重要的是，由于PLGA-pTA介导的PTT激活了抗肿瘤反应，远处肿瘤的进展以及肺转移也受到显著抑制。当进一步与抗程序性死亡受体1配体（a-PD-L1）抗体联合使用时，肿瘤生长和转移几乎被完全抑制。我们的研究提供了一个通用平台，可实现具有增强治疗效果的光热免疫联合治疗。
