Journal
BIOACTIVE MATERIALS
Volume 6, Issue 11, Pages 3812-3823Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.03.032
Keywords
Drug-resistance; Gallium-based compounds; Indocyanine green; Photodynamic therapy; Liver infection
Funding
- National Natural Science Foundation of China [81971667, 81671748]
- Key Research and Development Projection of Zhejiang Province [2020C03035]
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ICG-Ga NPs, a novel non-antibiotic nanoparticle, demonstrate excellent therapeutic effect against multidrug-resistant bacteria with the synergetic effect of photodynamic therapy and iron metabolism blocking, significantly improving treatment outcomes in cases of liver abscess and keratitis infection. The ultrasmall size allows rapid renal clearance without compromising biocompatibility, indicating potential for clinical treatment of bacterial infections and next-generation antibacterial agents.
Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics. Here, we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles (ICG-Ga NPs) containing clinically approved gallium (III) (Ga3+) and liver targeting indocyanine green (ICG) molecules to eradicate multi-drug resistant (MDR) bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking. The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane, further boost the endocytosis of Ga3+, then replace iron in bacteria cells to disrupt bacterial iron metabolism, and demonstrate the synergetic bacterial killing and biofilm disrupting effects. The ICG-Ga NPs show an excellent therapeutic effect against extended spectrum beta-lactamases Escherichia coli (ESBL E. coli) and significantly improve treatment outcomes in infected liver abscess and keratitis. Meanwhile, the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route, guaranteeing the biocompatibility. The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.
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