A powerful organic photosensitizer for effective treatment of malignant tumor via activating antitumor immune response.

Abstract

Photodynamic therapy (PDT) has emerged as an innovative approach in cancer treatment, effectively inducing tumor cell death through light-triggered reactive oxygen species (ROS) generation. Additionally, PDT can also trigger antitumor immune responses, thereby reducing the risk of postoperative tumor recurrence. However, the development of highly efficient photosensitizers aimed at activating immune responses for comprehensive tumor eradication remains at an early stage. In this study, we developed a new organic photosensitizer, ThC, which exhibits excellent mitochondrial-targeting effect and significantly enhanced ROS production compared to traditional photosensitizers, such as Chlorin e6 (Ce6). Our findings demonstrate that ThC robustly induces immunogenic cell death (ICD) process in hepatic cancer cells, which could effectively transform immunologically "cold" tumors into "hot" tumors. Through in situ injection and subsequent white light irradiation, ThC achieved superior efficacy in eliminating subcutaneous hepatic tumors compared to Ce6 treatment. Immunological analyses revealed that ThC treatment led to elevated levels of CD4+ and CD8+ T cells, along with a reduction in immunosuppressive cell populations (Tregs and tumor-associated macrophages) within the tumor microenvironment. This study provides a novel therapeutic agent with significant potential for clinical translation in the treatment of malignant tumors.