Coupling Probiotics with 2D CoCuMo‐LDH Nanosheets as a Tumor‐Microenvironment‐Responsive Platform for Precise NIR‐II Photodynamic Therapy

Abstract Photodynamic therapy (PDT) has become a promising cancer treatment approach with superior advantages. However, it remains a grand challenge to develop tumor microenvironment (TME)‐responsive photosensitizers (PSs) for tumor‐targeting precise PDT. Herein, the coupling Lactobacillus acidophilus ( LA ) probiotics with 2D CoCuMo layered‐double‐hydroxide (LDH) nanosheets ( LA &LDH) is reported as a TME‐responsive platform for precise NIR‐II PDT. The CoCuMo‐LDH nanosheets loaded on LA can be transformed from crystalline into amorphous through etching by the LA ‐metabolite‐enabled low pH and overexpressed glutathione. The TME‐induced in situ amorphization of CoCuMo‐LDH nanosheets can boost its photodynamic activity for singlet oxygen ( 1 O 2 ) generation under 1270 nm laser irradiation with relative 1 O 2 quantum yield of 1.06, which is the highest among previously reported NIR‐excited PSs. In vitro and in vivo assays prove that the LA &LDH can effectively achieve complete cell apoptosis and tumor eradication under 1270 nm laser irradiation. This study proves that the probiotics can be used as a tumor‐targeting platform for highly efficient precise NIR‐II PDT.