Photothermal nanocomposite reactivate "immune-hot" for triple-negative breast cancer treatment via glutamine metabolism reprograming.

Herein, a photothermal nanocomposite PAI@CB839 nanoparticles (NPs) was constructed to perform a heat-immune therapy for triple-negative breast cancer (TNBC). Firstly, a photothermal agent animated IR780 was modified on a mPEG-NH using 4,4'-dicarboxylazobenzene as a linker. The synthesized PAI exhibited superior photothermal efficiency of the IR780 even after assembling in water. As a functional carrier, PAI was used to load and deliver the glutaminase inhibitor CB839 to tumor tissue. In the hypoxic environment of tumor cells, the azo bond would break, triggering the release of cargo. Upon irradiation, the outstanding photothermal properties of IR780 resulted in tumor cell damage. This process could promote immunogenic cell death and program tumor to "immune-hot" condition. Concurrently, CB839 strengthened the antitumor immune response by remodulating the immunosuppressive TME through disturbing Glu abnormal metabolism, which further inhibited TNBC growth and metastasis. In conclusion, PAI@CB839 NPs exhibited great antitumor efficiency, which pave a new way for TNBC therapeutic regimen development.