Transforming the Tumor Microenvironment: An Outstanding AIE-Active Photosensitizer to Boost the Effectiveness of Immunotherapy

Immunotherapy, currently the most promising therapeutic approach for cancer, has shown significant efficacy. However, its clinical effectiveness is often constrained by such factors as tumor heterogeneity, the abundance of M2 macrophages, tumor-vascular hypoxia, and the immunosuppressive microenvironment created by immune checkpoint (IC) complexes. In this work, an effective photosensitizer (TSPA) with aggregation-induced emission (AIE) nature is adopted to counter above limitations. The synthesized TSPA demonstrated potent efficacy in eradicating primary tumors because of their effective generation reactive oxygen species (ROS) after undergoing photodynamic therapy (PDT) process. Moreover, TSPA can improve hypoxic conditions in tumor by normalizing blood vessels, and can instigate immunogenic cell death (ICD), thus stimulating immune cell activation. TSPA demonstrates the ability to reprogram M2 tumor-associated macrophages (TAMs) into the anti-tumor M1 phenotype, thereby increasing the infiltration of M1 macrophages within the tumor. This procedure notably ameliorates the immune microenvironment, effectively suppressing the long-term metastasis of breast cancer (BC). This research notably enhances the efficiency of tumor immunotherapy and is anticipated to emerge as a new strategy for improving the tumor's immunosuppressive microenvironment and overcoming immune evasion.