Dual-Ligand Janus Polymetformin/Polydopamine Nanoparticles for Immune/Photothermal/Photodynamic Therapy of Triple-Negative Breast Cancer

This study develops a dual-ligand modified Janus nanoplatform, termed PMPF (anti-PD-L1-PEG-SS@JPM@PEG-FA), for the synergistic treatment of triple-negative breast cancer (TNBC). First, metformin was polymerized with dopamine to prepare polymetformin/PDA nanoparticles (PM NPs). Then, PM NPs were modified by folic acid (FA) and anti-PD-L1 on the different sides via the Pickering emulsion method to obtain PMPF Janus NPs. The FA ligand ensures precise targeting of tumor cells and M2-type tumor-associated macrophages (TAMs), promoting their repolarization to the antitumoral M1 phenotype. Anti-PD-L1 blocks the PD-1/PD-L1 axis, activating CD8+ T cells for tumor immunotherapy. Moreover, PMPF served as an excellent photosensitizer, enabling near-infrared (NIR) irradiation-induced photothermal therapy (PTT) for the thermal ablation of tumor cells. Under NIR irradiation, PMPF also generates intracellular reactive oxygen species (ROS) to facilitate photodynamic therapy (PDT). In summary, the unique PMPF Janus nanoparticles represent an integrated platform for synergistic immune, photothermal, and photodynamic therapies, offering a safe, precise, and efficient nanotherapeutic strategy against TNBC.