Multifunctional mesoporous polydopamine nanoplatforms for synergistic photothermal-chemotherapy and enhanced immunotherapy in breast cancer treatment

Abstract

Breast cancer remains one of the most prevalent and deadly cancers among women worldwide, necessitating the development of more effective and comprehensive treatment strategies. In this study, we successfully synthesized mesoporous polydopamine (MPDA) with photothermal effects for the co-delivery of the chemotherapeutic drug doxorubicin (DOX) and the immune adjuvant imiquimod (R837), resulting in the development of a multifunctional nanoplatforms termed MDR. MDR displayed excellent photothermal conversion efficiency and pH-responsive drug release behavior. In vitro assessments revealed significant cytotoxicity of MDR against 4T1 cells under 808 nm laser irradiation, with enhanced cellular uptake in both 4T1 cells and bone marrow-derived dendritic cells (BMDCs). Additionally, the expression levels of the costimulatory molecules CD80 and CD86 were remarkably higher in the MDR-treated group than free R837 after co-incubation with immature BMDCs, indicating a stronger ability to promote BMDC maturation and effectively stimulate immune response activation. Intratumoral injection in breast cancer-bearing mice further demonstrated that the MDR + NIR group significantly inhibited tumor growth compared to other groups, with no apparent side effects. In conclusion, the multifunctional nanoplatforms integrating photothermal therapy, chemotherapy, and immunotherapy are expected to provide a novel therapeutic approach for the multimodal treatment of breast cancer.

Keywords: Breast cancer; Doxorubicin; Immunotherapy; Mesoporous polydopamine; Photothermal therapy; R837.