Abstract
Rapid increase of antimicrobial resistance has become an urgent threat to global public health. In this research, since photothermal therapy is a potential antibacterial strategy, which is less likely to cause resistance, a metal–organic framework-based chemo-photothermal combinational system was constructed. Zeolitic imidazolate frameworks-8 (ZIF-8), a porous carrier with unique features such as high loading and pH-sensitive degradation, was synthesized, and then encapsulated photothermal agent indocyanine green (ICG). First, ICG with improved stability in ZIF-8 (ZIF-8-ICG) can effectively produce heat in response to NIR laser irradiation for precise, rapid, and efficient photothermal bacterial ablation. Meanwhile, Zn2+ ions released from ZIF-8 can inhibit bacterial growth by increasing the permeability of bacterial cell membrane and further strengthen photothermal therapy efficacy by reducing the heat resistance of bacteria. Study showed that bacteria suffered from significant changes in morphology after treatment with ZIF-8-ICG under laser irradiation. The combinational chemo-hyperthermia therapy of ZIF-8-ICG could thoroughly ablate murine subcutaneous abscess induced by methicillin-resistant Staphylococcus aureus (MRSA), exhibiting a nearly 100% bactericidal ratio. Both in vitro and in vivo safety evaluation confirmed that ZIF-8-ICG was low toxic. Overall, our researches demonstrated that ZIF-8-ICG has great potential to be served as an alternative to antibiotics in combating multidrug-resistant bacterial pathogens.
Highlights
The widely spread bacterial pathogens used to be a serious threat to human health due to the lack of specific medicine and therapeutic measure
The return to the pre-antibiotic era has become a reality in many parts of the world because of the rapid emergence of multidrug-resistant (MDR) bacterial pathogens, such as “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa (P. aeruginosa) and Enterobacter species) [3,4,5]
In order to investigate the biocompatibility of indocyanine green (ICG)-loaded nanoparticles, the in vitro cytotoxicity was performed in 293T cell lines using the CCK-8 viability assay and the cells were obtained from Chinese Academy of Sciences Cell Bank (Shanghai, China)
Summary
The widely spread bacterial pathogens used to be a serious threat to human health due to the lack of specific medicine and therapeutic measure. Recent researches showed that failing to manage MDR bacterial infections may cause more than 10 million deaths per year and cost up to 100 trillion dollars by 2050 [6,7]. In this situation, it is quite imperative to develop alternative therapeutic strategies for bacterial infection with minimizing resistance emergence. We expected to demonstrate that ZIF-8-ICG was a nanosystem combining the chemo-photothermal therapy together, which possessed efficient localized chemo-photothermal bacterial ablation and disinfection activities and was recognized as an effective weapon in combating the growing threat of MDR bacteria. SScchheemme a1t.icSchilelmuastticrailtliuostnratoiofn tohfethcehcehmemoo--pphhootottohtehrmearlmcoaml bcinoamtiobnianl antainoonsyasltemnafnorosthyestem for the treatment of tmreaettmheinctilolfinm-ertehsiciislltina-nretsiSsttaanpthSytalpohcyolocccouccsusaauurreeuuss(M(MRSRAS)Ain)feicntiofen.ction
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