Bioinspired Heteromultivalent Ligand-Decorated Nanotherapeutic for Enhanced Photothermal and Photodynamic Therapy of Antibiotic-Resistant Bacterial Pneumonia

Abstract

Pseudomonas aeruginosa can cause a multitude of inflammations in humans. Due to its ability to form biofilm, the bacteria show durable resistance to drugs. Herein, we developed a heteromultivalent ligand-decorated nanotherapeutic inspired by living system for inhibition of antibiotic-resistant bacterial pneumonia. The nanotherapeutic with a heteromultivalent glycomimetic shell can specifically recognize P. aeruginosa to inhibit its biofilm formation and protect native cells from bacterial infection; the rate of biofilm inhibition was up to 85%. The nanotherapeutic with a bioresponsive hydrophobic core can protonate and control drug release in the microenvironment of bacterial infections. By utilizing these properties, the nanotherapeutics can effectively penetrate the internal structure of biofilms to release the drug, dispersing the biofilm by over 80% under laser irradiation. In vivo bioinspired nanotherapeutics have the potential to efficiently inhibit antibiotic-resistant P. aeruginosa-induced pneumonia. Collectively, we expect biomimicking systems to be the next generation of prevention and treatment as integrated antibacterial agents against P. aeruginosa.