Ultrasmall Ga-ICG nanoparticles based gallium ion/photodynamic synergistic therapy to eradicate biofilms and against drug-resistant bacterial liver abscess

Tingting Xie; Yuchen Qi; Yangyang Li; Feilu Zhang; Wanlin Li; Danni Zhong; Zhe Tang; Min Zhou

doi:10.1016/j.bioactmat.2021.03.032

Ultrasmall Ga-ICG nanoparticles based gallium ion/photodynamic synergistic therapy to eradicate biofilms and against drug-resistant bacterial liver abscess

Bioact Mater. 2021 Apr 10;6(11):3812-3823. doi: 10.1016/j.bioactmat.2021.03.032. eCollection 2021 Nov.

Authors

Tingting Xie^{1

2}, Yuchen Qi², Yangyang Li², Feilu Zhang³, Wanlin Li², Danni Zhong², Zhe Tang⁴, Min Zhou^{1

2}

Affiliations

¹ Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
² Institute of Translational Medicine, Zhejiang University, Hangzhou, 310009, China.
³ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
⁴ Department of Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, China.

Abstract

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 β-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.

Keywords: Drug-resistance; Gallium-based compounds; Indocyanine green; Liver infection; Photodynamic therapy.