Glycomimetic-Conjugated Photosensitizer for Specific Pseudomonas aeruginosa Recognition and Targeted Photodynamic Therapy

Zhao, Y (Zhao, Yu)^[ 1 ] ; Lu, ZT (Lu, Zhentan)^[ 1 ] ; Dai, XM (Dai, Xiaomei)^[ 1 ] ; Wei, XS (Wei, Xiaosong)^[ 1 ] ; Yu, YJ (Yu, Yunjian)^[ 1 ] ; Chen, XL (Chen, Xuelei)^[ 1 ]; Zhang, XG (Zhang, Xinge)^[ 1 ] ; Li, CX (Li, Chaoxing)^[ 1 ]

BIOCONJUGATE CHEMISTRY, 2018, 29(9): 3222-3230

DOI: 10.1021/acs.bioconjchem.8b00600

 WOS:000445439500036

Abstract

Due to the rapid development of bacterial resistance, there is an urgent need to explore new antibacterial agents to substitute for traditional antibiotic therapy. Photodynamic therapy has been identified as a promising bactericidal method to conquer antibiotic-resistant pathogens. To solve the problem of photosensitizer damage to normal tissues in vivo, we developed a boron-dipyrrolemethene (BODIPY)-based glycosylated photosensitizer for ablating Pseudomonas aeruginosa (P. aeruginosa). This glycosylated photosensitizer exhibited good water solubility and generated 102 rapidly in an aqueous solution under light exposure. The photosensitizer did not cause detectable toxicity to human cells in the dark. Importantly, the photosensitizer was able to selectively attach to P. aeruginosa over normal cells, thus resulting in effective pathogen ablation by reactive oxygen species. Moreover, the photosensitizer inhibited over 90% of the biofilm formation produced by P. aeruginosa. The results indicate that the design of the macromolecular photosensitizer-induced bacterial death and inhibited biofilm formation provide a novel strategy for overcoming bacterial infection.