Red-Light-Activatable AND-Gated Antitumor Immunosuppressant

Abstract

Immunosuppressants are emerging as promising candidates for cancer therapy with lower cytotoxicity compared to traditional chemotherapy drugs; yet, the intrinsic side effects such as immunosuppression remain a critical concern. Herein, we introduce a photoactivatable antitumor immunosuppressant called dmBODIPY-FTY720 (BF) that shows no cytotoxicity but can be temporally and locally activated by deep-red light illumination to induce tumor cell apoptosis. To further reduce potential side effects, we integrate BF with another classic photosensitizer called methylene blue (MB) that is activated under the same wavelength of deep-red light (>650 nm) and successfully establish a red-light-activatable AND Boolean logic gate through a mechanism that we found to be synergetic apoptotic induction. At further decreased dosages, deep-red light illumination does not induce cell death in the presence of either BF or MB, but significant cancer cell death is triggered in the presence of both drugs. Therefore, the dosage of BF is further reduced, which will be highly beneficial to minimize any potential side effects of BF. This AND-gated strategy has been successfully applied in vivo for effective suppression of hepatocarcinoma tumors in living mice.