Dual-Sensitive PEG-Sheddable Nanodrug Hierarchically Incorporating PD-L1 Antibody and Zinc Phthalocyanine for Improved Immuno-Photodynamic Therapy

• DOI: 10.1021/acsami.0c20422
• Publication Date: 2021-03-12T11:38:33Z
• Authors: Zhenwei Su; Zecong Xiao; Jinsheng Huang; Yong Wang; Yongcheng An; Hong Xiao; Yuan Peng; Pengfei Pang; Shisong Han; Kangshun Zhu; Xintao Shuai
• Keywords: Combination therapy; Immune checkpoint

Tumor immunotherapy like immune checkpoint blockade (ICB) shows great success nowadays but is severely limited by low response rates and immune-related adverse events (IRAEs). While photodynamic therapy (PDT) could efficiently eradicate tumor cells further induce responses to promote activating of T lymphocytes. Herein a nanodrug hierarchically incorporating photosensitizer PD-L1 antibody was developed for synergistic immuno-photodynamic therapy. A pH/enzyme dual-sensitive polymeric micelle with sheddable PEG coating designed codelivery zinc phthalocyanine (ZnPc) in the tumor. The microenvironment featuring pH high matrix metallopeptidase 2 (MMP-2) sequentially triggered shedding release exert local ICB tissue, after which remaining ZnPc undergoing charge reversal readily delivered into cells. With light irradiation, effect sAMPc induced immunogenic cell death promoted intratumor recruitment CD8+ cells, thus resulting ICB. Moreover, PEG-sheddable strategy endowed stealth properties blood circulation, making IRAEs significantly reduced. This pH/MMP-2 provids promising well-combined PDT achieve improved anticancer reduced effects.