Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer

Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE. staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.