|Title:||Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment||Authors:||Chiou, Yi-Ru
Harroun, Scott G.
|Keywords:||ONE-STEP SYNTHESIS;QUANTUM DOTS;ANTIBACTERIAL ACTIVITY;NANOPARTICLES;INFLAMMATION;MORTALITY;SEPSIS||Issue Date:||18-Aug-2022||Publisher:||ROYAL SOC CHEMISTRY||Journal Volume:||14||Journal Issue:||32||Start page/Pages:||11719-11730||Source:||NANOSCALE||Abstract:||
Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer dots (CPDs(Man/AA)) from a mixture of mannose (Man) and positively charged amino acids [AAs; lysine, arginine (Arg), or histidine] through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDs(Man/AA) showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDs(Man/Arg) is ca. 1.0 mu g mL(-1), which is comparable to or lower than those of other tested antibiotics (e.g., ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDs(Man/Arg) feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis. In vitro cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDs(Man/AA). In addition, in vivo studies on methicillin-resistant Staphylococcus aureus-infected mice treated with the CPDs(Man/Arg) showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDs(Man/AA) is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDs(Man/Arg), including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.
|Appears in Collections:||生命科學暨生物科技學系|
03 GOOD HEALTH AND WELL-BEING
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