Immunomodulating platelet-mimicking nanoparticles for AIE-based enhanced photodynamic immunotherapy against lung cancer

Lung cancer has become the leading cause of cancer related death worldwidely. Nowadays, immune checkpoint inhibitor (ICI) plays an important part in the treatment of lung cancer. However, immunologically cold tumor microenvironment (TME) hinders the therapeutic effect of ICIs. Herein, immunomodulating platelet-mimicking nanoparticles (DM@PM NPs) were designed by encapsulating the aggregation-induced emission (AIE) photosensitizer DTZ-TPA-DCN with acidic-sensitive bond modified DSPE-PEG-MET (MET, metformin) and then coating with a platelet membrane (PM). Notably, DM@PM NPs can selectively accumulate in tumor profiting from the tumor-targeting and antiphagocytic capabilities of PM. In the acidic tumor tissues, the acidic-sensitive released MET of DSPE-PEG-MET plays as a kind of ICI and degrades PD-L1 expression in TME. MET also facilitates AIE photosensitizer induced photodynamic therapy (PDT) via blocking mitochondrial oxidative phosphorylation, thus dramatically promotes immunogenic cell death (ICD) of tumor cells which could convert cold tumor to hot and facilitates MET realizing enhanced immunotherapy against cancer in turn. What's more, sub-lethal ROS induced by DM@PM NPs could also directly activate immune cells. Overall, we proposed an intelligent and cross-regulatory platelet-mimicking drug loading nano-carrier that could achieve photodynamic immunotherapy against in situ and distant tumors, which provides a potential for clinical therapy of lung cancer.