Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria
The stalling development of antibiotics, especially against intrinsically resistant Gram-negative pathogens associated with outer membranes, leads to an emerging antibiotic crisis across the globe. To breathe life into existing drugs, we herein report a hypoxia-responsive nanoparticle (NP) that encapsulates a hydrophobic antibiotic, rifampicin, and a cationic potentiator, polysulfonium. The simultaneous release of antibiotics and potentiators can be promoted and inhibited in response to the severity of bacterial-induced hypoxia, leading to antimicrobial dosing in a precision manner. Under the synergism of polysulfoniums with membrane-disruption capability, the NPs can intensively decrease the antibiotic dose by up to 66-95% in eliminating planktonic Gram-negative P. aeruginosa bacteria and achieve an 8-log reduction of bacteria in mature biofilms at rifampicin MIC. The NP formulation demonstrates that precision dosing of antibiotics and potentiators regulated by hypoxia provides a promising strategy to maximize efficacy and minimize toxicity in treating Gram-negative bacterial infection.
National Natural Science Foundation of China ; opening Foundation of State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology[oic-202301011]
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1.Hubei Key Laboratory of Material Chemistry and Service Failure,Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,School of Chemistry and Chemical Engineering,Huazhong University of Science and Technology,Wuhan,Hubei,430074,China
2.College of Chemistry,Liaoning University,Shenyang,110036,China
3.Taizhou Research Institute,Southern University of Science and Technology,Taizhou,Zhejiang,318001,China
Bai，Weiguang,Hu，Yongjin,Zhao，Jinghua,et al. Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria[J]. ACS Macro Letters,2023,12(9):1193-1200.
Bai，Weiguang.,Hu，Yongjin.,Zhao，Jinghua.,Shi，Liuqi.,Ge，Chunhua.,...&Rao，Jingyi.(2023).Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria.ACS Macro Letters,12(9),1193-1200.
Bai，Weiguang,et al."Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria".ACS Macro Letters 12.9(2023):1193-1200.
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