Bacteria-Targeting Photodynamic Nanoassemblies for Efficient Treatment of Multidrug-Resistant Biofilm Infected Keratitis

Multidrug-resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) cannot be extirpated with any of the antipseudomonal antibiotics available in clinic because P. aeruginosa exhibit natural resistance to antibiotics and form a stable biofilm. Biofilm formed by P. aeruginosa is a leading cause of bacterial keratitis which may cause corneal perforation and even blindness. Antibacterial photodynamic therapy (aPDT) is a promising bactericidal method in combatting drug-resistant bacteria. Unfortunately, the use of broad-spectrum aPDT that kills bacteria indiscriminately may lead to microbiota imbalance and cause serious side effects in normal cells. Herein, P alpha Gal(50)-b-PGRB(20), which can effectively disperse biofilms and selectively kill MDR-P. aeruginosa inside biofilms by binding to Lec A in the extracellular polymeric substances and on the P. aeruginosa membrane with low phototoxicity caused by broad-spectrum aPDT, is designed and synthesized. P alpha Gal(50)-b-PGRB(20) has bactericidal activities by damaging DNA, RNA, protein, and membrane. In vivo study of the MDR-P. aeruginosa biofilm infected keratitis model demonstrates the potential of P alpha Gal(50)-b-PGRB(20) for a better corneal recovery. This work provides a dedicated antibacterial material for preferentially killing MDR-P. aeruginosa over normal cells and other bacteria.