Mesoporous dopamine coated copper indium selenium nanosystem for enhanced photoimmunotherapy via regulating methionine metabolism.

Methionine can not only regulate the growth of cancer cells but also promote the activity of cytotoxic T lymphocytes. Therefore, the efficacy of multimodal synergistic therapy can be improved through regulating methionine metabolism. In this work, large neutral amino acid transporter protein 1 inhibitor (BCH) loaded and mesoporous polydopamine coated copper indium selenide nanosystem (CPB) was developed for improving photoimmunotherapeutic efficacy. On the one hand, CPB can induce immunogenic cell death and recruit cytotoxic T lymphocytes (CTLs) through its photothermal, photodynamic and chemodynamic properties; on the other hand, CPB can not only release BCH for blocking the uptake of methionine by cancer cells but also produce reactive oxygen species for inhibiting the endogenous synthesis of methionine in cancer cells via oxidize intracellular polyamines, collectively reducing methionine levels in cancer cells, thus inhibiting the growth of tumors. More importantly, methionine that is not endocytosed by cancer cells can be utilized by CTLs to improve immunotherapeutic efficacy. Both in vitro and in vivo experiments demonstrate the therapeutic efficacy of CPB against tumors by regulating methionine metabolism. The development of CPB nanosystem can effectively improve cancer therapeutic efficacy through regulating methionine metabolism in tumor tissues, providing a potential strategy for multimodal synergistic therapy against tumors.