Noncovalent Co-Assembly of Aminoglycoside Antibiotics@tannic Acid Nanoparticles for Off-the-shelf Treatment of Pulmonary and Cutaneous Infections

Antibiotics still serve as the first choice for combating bacterial infections, whereas the therapeutic efficiency of antibiotics needs to be further augmented. Here, we report the spontaneous, generalized noncovalent coassembly of aminoglycoside antibiotics (AGs) with tannic acid (TA) through electrostatic and hydrogen-bond interactions to form nanoparticles in water as off-the-shelf antibacterial agents. Specially, tobramycin@TA nanoparticles (Tob@TA NPs) elicited superior sterilization efficacy over native Tob against both Gram-positive and Gram-negative bacterial strains by enhancing the attachment onto the bacteria surface and the production of intracellular reactive oxygen species (ROS), disturbing membrane potential and promoting the leakage of bioactive substance such as DNA. Importantly, Tob@TA NPs also showed enhanced antibacterial efficacy against Tob-resistant Pseudomonas aeruginosa (P. aeruginosa). In P. aeruginosa-induced acute pneumonia model, the administration of Tob@TA NPs could eliminate bacterial infection and reduce inflammation. Furthermore, coassembled Tob@TA NPs loaded in adhesive gelatin hydrogel dressing significantly accelerated the healing of P. aeruginosa-infected skin wound by effectively eradicating bacteria, decreasing inflammation and improving angiogenesis. Taking together, our findings provide a facile, simple and effective methodology to construct ready-to-use aminoglycoside antibiotics@TA NPs for the eradication of bacterial infection in clinic.