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 of single-mode cancer therapies. Here, we develop a near-infrared (NIR) light-activated biomimetic nanomotor for targeted nitric oxide (NO) delivery and synergistic cancer therapy. The nanomotor is constructed from bowl-shaped mesoporous polydopamine nanoparticles loaded with Fe(II) as a Fenton catalyst and BNN6 as a thermally responsive NO donor (denoted as PFB). To endow tumor specificity, the nanomotor is further camouflaged with MCF-7 cancer cell membrane (PFB@CM), enabling homologous recognition and enhanced intratumoral accumulation. Upon NIR irradiation, PFB@CM exhibits strong photothermal conversion efficiency that initiates 3 synergistic processes: (a) self-thermophoretic propulsion that promotes cellular internalization; (b) heat-triggered decomposition of BNN6 for precise NO release; and (c) heat-accelerated Fe(II) release from the polydopamine matrix. The liberated Fe(II) catalyzes endogenous H₂O₂ via a Fenton-like reaction to generate reactive oxygen species, which subsequently react with NO to yield highly cytotoxic reactive nitrogen species. This cascade amplifies oxidative and nitrosative stress within tumor cells, enabling photothermal, chemodynamic, and NO-mediated synergistic therapy. The design of PFB@CM integrates homologous targeting, autonomous motility, and NIR-responsive multimechanism activation, demonstrating a versatile strategy for precision nanomedicine and highlighting the potential of light-activated nanomotors for safe and effective multimodal cancer therapy.