One-step synthesized NIR-responsive polydopamine nanoparticles for synergistic nitric oxide chemotherapy and photothermal therapy against multidrug-resistant bacteria.

To address the global challenge of multidrug-resistant bacteria (MDRB), this study developed near-infrared (NIR)-responsive polydopamine nanoparticles (PDA NP-BNN6) that synergize nitric oxide (NO)-mediated chemotherapy and photothermal therapy (PTT). A one-step synthesis strategy was employed to simultaneously encapsulate the NO donor BNN6 and fabricate PDA nanoparticles, achieving a high drug-loading efficiency of 35.05% while significantly simplifying the preparation process. The optimized formulation (PDA NP-BNN6-20) exhibited efficient photothermal conversion (ΔT = 23.7 °C), excellent cyclic stability, and precise NIR-triggered NO release under 808 nm irradiation. Quantitative assays demonstrated remarkable synergistic antibacterial rates of 92.54% against S. aureus and 92.03% against E. coli after 25 min of irradiation. Morphological analysis revealed severe membrane disruption under combined NO/PTT treatment, corroborating the dual-action mechanism. Additionally, the nanoparticles showed favorable hemocompatibility (hemolysis < 2%) and good colloidal stability. By integrating efficient one-step synthesis, controlled NO release, and potent photothermal activity, this work presents a streamlined and effective antibacterial nanoplatform, offering a promising proof-of-concept for localized anti-infective therapy, particularly for biofilm-associated and device-related infections.