Chimeric Peptide‐Engineered Self‐Delivery Nanomedicine for Photodynamic‐Triggered Breast Cancer Immunotherapy by Macrophage Polarization

Abstract A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide‐engineered self‐delivery nanomedicine (designated as ChiP‐CeR) for photodynamic‐triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP‐CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc‐K(Fmoc)‐PEG 8 ‐CREKA. ChiP‐CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high‐mobility group box‐1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP‐CeR can also polarize M2‐type tumor‐associated macrophages (TAMs) into M1‐type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP‐CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.