Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer

The occurrence and progression of tumors is highly correlated with tumor cell proliferation and evasion of the immune surveillance system [ 1 , 2 , 3 ]. Recently, studies on photodynamic therapy (PDT) and its potential anti-tumor immune responses have profoundly elucidated the complex interaction between tumor cells and the immune system [ 4 , 5 , 6 , 7 , 8 ]. Therefore, new therapeutic strategies aim to remove tumor cells and/or trigger the immune system to destroy the tumor [ 9 , 10 , 11 ]. Several anti-tumor immunotherapy strategies have been reported recently. In particular, anti-CTLA-4 and PD-L1/PD1 antibodies have been successfully used for anti-tumor immunotherapy by blocking the immune escape pathway adopted by tumors [ 12 , 13 , 14 ]. A systematic anti-tumor effect has been reported by combining photodynamic therapy with immune checkpoint inhibitors—proteins that activate immune T cells, allowing them to kill cancer cells [ 15 , 16 , 17 ]. PDT, in particular, is unique because unlike radio- and chemo-therapy, which suppress the immune system, PDT kills malignant cells and stimulates the host immune system to invade the tumor. The problem that lies in the photosensitizers used in PDT is that they have poor photo- and thermal stability [ 18 , 19 ], rapidly clearing from the blood [ 20 , 21 ], not accumulating sufficiently in the targeted tumor and low singlet oxygen production due to the hypoxic tumor microenvironment [ 22 , 23 ]. These drawbacks inevitably cause inefficient therapeutic effects that might stop the body to trigger robust immune responses so as to completely eradicate the remaining tumor cells.