A PTT-Induced Feed-Back Carbon Nanosystem for Enhanced Breast Cancer Therapy by Extracellular Matrix Remodeling

In the treatment of breast cancer, the dense extracellular matrix (ECM) severely impedes drug delivery and immune cell infiltration, resulting in poor therapeutic effects. Photothermal therapy (PTT) has achieved promise in preclinical breast cancer studies. However, in tumor immunogenic cell death (ICD) induced by PTT, immune cells are almost confined around the tumor periphery due to the ECM, which weakens the immune response. Thus, this study developed a carbon nanosystem (LCTi) to explore the effectiveness of enhancing PTT through the ECM remodeling. After intravenous injection, LCTi accumulated in the tumor through iRGD-mediated active targeting, subsequently destroying tumor cells and inducing ICD under 808 nm laser irradiation. Simultaneously, losartan was photothermal-responsively released from LCTi to remodel the ECM, consequently enhancing PTT efficacy by alleviating hypoxia and improving the tumor immune microenvironment. Focusing on ECM remodeling, this study provides an attractive "PTT-reinforced PTT" feed-back strategy for future breast cancer therapy.