Electron compensation‐gated nanomotor for immunomodulation and microenvironment remodeling in bacterial pneumonia therapy

Abstract

Bacterial pneumonia treatment is severely hampered by escalating antibiotic resistance and physiological drug delivery barriers. To address these critical challenges, we report the development of an intelligent biomimetic Janus nanomotor (MAgAu@CM) featuring a built‐in “electronic lock” for spatiotemporally controlled on‐demand therapy. The nanomotor is constructed from a melanin‐supported AgAu alloy and camouflaged with an erythrocyte and platelet hybrid membrane, ensuring prolonged systemic circulation and active inflammation targeting. Crucially, the potent silver component remains therapeutically inert during circulation due to a highly stable electronic compensation mechanism. Upon near‐infrared irradiation at the target infection site, the localized photothermal effect acts as a specific “key.” This thermal intervention not only provides direct hyperthermic ablation of the pathogens but also disrupts the electronic equilibrium, triggering the burst release of bactericidal Ag + for powerful synergistic chemo‐photothermal eradication. Concurrently, this photothermal input overclocks the inherent nanozyme activity of the nanomotor, catalyzing the decomposition of endogenous H 2 O 2 to generate robust oxygen‐driven mechanical propulsion for deep penetration into complex infectious biofilms. Furthermore, this system actively remodels the hostile pathological microenvironment by alleviating local hypoxia and promoting the functional polarization of macrophages toward a tissue‐repairing M2 phenotype. By integrating biomimetic stealth, active navigation, stimuli‐responsive propulsion, and microenvironment remodeling, this multifunctional nanoplatform establishes a highly promising translational paradigm for combating deep‐seated and multidrug‐resistant bacterial infections.