Codelivery of Anti ‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Matrix metalloproteinase and pH dual ‐sensitive micelles for anti‐PD‐1 antibody (aPD‐1) and paclitaxel (PTX) delivery are described. Sheddable polyethylene glycol (PEG) enhances the tumor accumulation of nanodrug and achieves intratumor immune activation. The nanodrug shows programmed site‐specific release of aPD‐1 and PTX in tumor tissue and tumor cells, respectively, resulting in a synergistic antitumor effect with chemoimmunotherapy. AbstractImmune 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), w hile 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 b oost 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 ...

Source: Small - February 28, 2020 Category: Nanotechnology Authors: Zhenwei Su, Zecong Xiao, Yong Wang, Jinsheng Huang, Yongcheng An, Xu Wang, Xintao Shuai Tags: Full Paper Source Type: research