Synergistic Effect of Photothermally Targeted NIR-Responsive Nanomedicine-Induced Immunogenic Cell Death for Effective Triple Negative Breast Cancer Therapy.

Triple negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have approved targeted therapy. Therefore, patients primarily depend on forceful systemic chemotherapy that has unavoidable harmful side effects, resulting in inadequate therapeutic outcomes and leading to a high mortality rate. Hence, there is an urgent need to develop targeted therapies for the TNBC populace. Developing a new nanotherapeutic approach of combinational therapy could be an effective alternative strategy. Therefore, we designed a combination of hyaluronan (HA)-polyaniline (PANi)-imiquimod (R837), denoted as HA-PANi/R837, nanoparticles (NPs) that exhibited a high extinction coefficient of 8.23 × 108 M-1 cm-1 and adequate photothermal conversion efficiency (PCE) (η = 41.6%), making them an efficient photothermal agent (PTA) that is highly beneficial for selective CD44-mediated photothermal ablation of TNBC tumors. Furthermore, co-encapsulation of R837 (toll-like receptor 7 agonist) immunoadjuvant molecules triggers an immune response against the tumor. The formed CD44-targeted HA-PANi/R837 NPs' selectivity incinerates the tumor under near-infrared (NIR)-triggered photothermal ablation, generating tumor-associated antigens and triggering R837 combination with anti-CTLA-4 for immunogenic cell death (ICD) activation to kill the remaining tumor cells in mice and protect against tumor relapse and metastasis. Our results demonstrated that novel HA-PANi/R837 NP-induced photothermal ICD achieved in CD44-targeted TNBC is a promising application.