Mesoporous polydopamine-based biomimetic nanoplatform for immunotherapy of multiple myeloma by homologous targeting and systemic immune activation

Photothermal therapy (PTT) not only directly eliminates tumors through its photothermal effects but also triggers a critical antitumor immune response. This study created a multifunctional nanoplatform out of biodegradable mesoporous polydopamine (mPDA). By doping manganese ions (Mn 2+ ) to generate mPDA@Mn nanoparticles, the material's photothermal conversion efficiency was greatly improved, as was the efficient loading of the anticancer medication carfilzomib. This system enables precise control over the release of CFZ and Mn 2+ under near-infrared (NIR) irradiation, achieving triple synergistic antitumor effects through chemotherapy, photothermal therapy, and immune activation at the tumor site. In vitro experiments demonstrated that the cell membrane-coated CM@mPDA@Mn/CFZ nanosystem exhibits favorable biocompatibility. In a mouse model of multiple myeloma, the combination of this nanosystem with NIR irradiation showed significant synergistic therapeutic efficacy. It not only destroyed tumor cells directly, but it also stimulated dendritic cell (DC) maturation, CD3 + T cell activation, and cytotoxic T lymphocyte (CTL) infiltration, substantially modifying the tumor immune microenvironment. These findings suggest that this triple synergistic method, which combines chemotherapy, photothermal ablation, and immune activation, provides an effective and targeted nanotherapeutic platform for the treatment of multiple myeloma.