Self-propelled galactose- targeted nanomotors enabling synergistic photothermal/gas therapy for antibiotic-free eradication of Pseudomonas aeruginosa biofilms

To address the dual challenges of antibiotic resistance and physical barrier in Pseudomonas aeruginosa ( PA ) biofilm infection, a near-infrared light responsive nitric oxide (NO) releasing asymmetric nanomotor (MAGN) was developed to achieve efficient anti-infection through the triple strategy of “targeted recognition - autonomous penetration- synergistic antibacterial”. The MAGN surface modification of galactose enables it to actively target bacteria, thereby enhancing its accumulation at the infection site. Under the irradiation of 808 nm near-infrared light, MAGN generates heat, which on the one hand promotes the dispersion of biofilms, and on the other hand triggers the loaded nitrosoglutathione (GSNO) molecules to release NO gas. The released NO gas not only drives the autonomous movement by activating the asymmetric propulsion mechanism of MAGN to further enhance its permeability but also works in synergy with the photothermal effect to exert antibacterial efficacy deep in the infected site. In a mouse model infected with PA , MAGN demonstrated a remarkable biofilm-eliminating capability in the absence of antibiotics. In conclusion, MAGN establishes a pioneering platform that leverages targeted multi-modal synergy to achieve highly effective, antibiotic-free eradication of recalcitrant PA biofilm infections.