NIR-Propelled Biomimetic Nanomotors for Photothermal/Chemodynamic/NO Synergistic Tumor Therapy

Multimodal nanotherapeutic systems capable of integrating photothermal, catalytic,and gas-mediated strategies offer powerful opportunities to overcome the limitations ofsingle-mode cancer therapies. Here, we develop a near-infrared (NIR) light-activatedbiomimetic nanomotor for targeted NO delivery and synergistic cancer therapy. Thenanomotor is constructed from bowl-shaped mesoporous polydopamine (PDA)nanoparticles loaded with Fe(II) as a Fenton catalyst and BNN6 as a thermallyresponsive NO donor (Denoted as PFB). To endow tumor specificity, the nanomotor isfurther camouflaged with MCF-7 cancer cell membrane (PFB@CM), enablinghomologous recognition and enhanced intratumoral accumulation. Upon NIRirradiation, PFB@CM exhibits strong photothermal conversion efficiency that initiatesthree synergistic processes: (i) self-thermophoretic propulsion that promotes cellularinternalization; (ii) heat-triggered decomposition of BNN6 for precise NO release; and(iii) heat-accelerated Fe(II) release from the PDA matrix. The liberated Fe(II) catalyzesendogenous H2O2 via a Fenton-like reaction to generate reactive oxygen species (ROS),which subsequently react with NO to yield highly cytotoxic reactive nitrogen species(RNS). This cascade amplifies oxidative and nitrosative stress within tumor cells,enabling photothermal, chemodynamic, and NO-mediated synergistic therapy. Thedesign of PFB@CM integrates homologous targeting, autonomous motility, and NIR-responsive multi-mechanism activation, demonstrating a versatile strategy for precisionnanomedicine and highlighting the potential of light-activated nanomotors for safe andeffective multimodal cancer therapy.