The fact that increasing antibiotic resistance of pathogenic bacteria and a lack of new potent broad-spectrum antibiotics call for the development of alternative approaches for treating infectious diseases. With the merits of great efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents an attractive modality for this purpose. Here, we report that the newly fabricated photodynamic chitosan nano-assembly, designated CS-Ce6, could synergistically kill antibiotic-resistant bacteria with superior potency to vancomycin. CS-Ce6 nano-assembly, obtained from covalent conjugate of chlorin e6 (Ce6) with chitosan, exhibited strong association with bacteria, thus altering their morphologies and mediating great delivery efficiency of Ce6. Upon light irradiation, localized generation of singlet oxygen by CS-Ce6 nano-assembly has a remarkable bactericidal effect toward both drug-resistance Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Acinetobacter baumannii, which was greater than that the free Ce6 and antibiotics had. We also confirmed that APDT-treated MRSA neither developed resistance to APDT nor altered their resistance to methicillin. Our in vivo studies demonstrated that the CS-Ce6 nano-assembly had comparable therapeutic efficacy with vancomycin in MRSA-infected mice. These results suggest that APDT by photodynamic chitosan nano-assembly hold great potential in combating antibiotic-resistant bacteria and hopefully in reducing the need of antibiotics in the future.

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