A phthalocyanine-based photosensitizer for effectively combating triple negative breast cancer with enhanced photodynamic anticancer activity and immune response

Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive oxygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and invasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy. [Display omitted] •A novel molecular photosensitizer was designed based on phthalocyanine and IDO inhibitor.•Conjugation of 1-MT promoted the cellular uptake and ROS generation of 1-MT-Pc.•1-MT-Pc showed the optimum anticancer efficacy in vitro and in vivo.•1-MT-Pc exhibited effective inhibition of 4T1 cells migration and invasion, and pulmonary metastasis.•1-MT-Pc elevated the intratumoral infiltration of CD8+ T lymphocytes and CD19+ B lymphocytes.