PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510275, P. R. China.
College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, P. R. China.
Small. 2020 Feb;16(7):e1906832. doi: 10.1002/smll.201906832. Epub 2020 Jan 28.
Immune checkpoint blockade (ICB) is demonstrating great potential in cancer immunotherapy nowadays. Yet, the low response rate to ICB remains an urgent challenge for tumor immunotherapy. A pH and matrix metalloproteinase dual-sensitive micellar nanocarrier showing spatio-temporally controlled release of anti-PD-1 antibody (aPD-1) and paclitaxel (PTX) in solid tumors is prepared to realize synergistic cancer chemoimmunotherapy. Antitumor immunity can be activated by PTX-induced immunogenic cell death (ICD), while aPD-1 blocks the PD-1/PD-L1 axis to suppress the immune escape due to PTX-induced PD-L1 up-regulation, thus resulting in a synergistic antitumor chemoimmunotherapy. Through decoration with a sheddable polyethylene glycol (PEG) shell, the nanodrug may better accumulate in tumors to boost the synergistic antitumor treatment in a mouse melanoma model. The present study demonstrates a potent antitumor chemoimmunotherapy utilizing tumor microenvironment-sensitive micelles bearing a sheddable PEG layer to mediate site-specific sequential release of aPD-1 and PTX.
免疫检查点阻断（ICB）在癌症免疫治疗中展现出巨大的潜力。然而，ICB 的低应答率仍然是肿瘤免疫治疗的一个紧迫挑战。本文制备了一种 pH 和基质金属蛋白酶双重敏感的胶束纳米载体，可在实体瘤中实现时空控制释放抗 PD-1 抗体（aPD-1）和紫杉醇（PTX），以实现协同的癌症化疗免疫治疗。PTX 诱导的免疫原性细胞死亡（ICD）可激活抗肿瘤免疫，而 aPD-1 阻断 PD-1/PD-L1 轴，以抑制由于 PTX 诱导的 PD-L1 上调引起的免疫逃逸，从而导致协同的抗肿瘤化疗免疫治疗。通过修饰可脱落的聚乙二醇（PEG）壳，纳米药物可以更好地在肿瘤中积累，以增强在小鼠黑色素瘤模型中的协同抗肿瘤治疗效果。本研究利用具有可脱落 PEG 层的肿瘤微环境敏感胶束，实现了 aPD-1 和 PTX 的位点特异性顺序释放，展示了一种有效的抗肿瘤化疗免疫治疗方法。
