Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment

Yi-Ru Chiou; Chin-Jung Lin; Scott G. Harroun; Yi-Ru Chen; Lung Chang; An-Tai Wu; Fu-Chieh Chang; Yang-Wei Lin; Han-Jia Lin; Anisha Anand; Binesh Unnikrishnan; Amit Nain; Chih-Ching Huang

doi:10.1039/D2NR01959K

Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment†

Yi-Ru Chiou,‡^a Chin-Jung Lin,‡^b Scott G. Harroun,^c Yi-Ru Chen,^b Lung Chang,^d An-Tai Wu,*^e Fu-Chieh Chang,^df Yang-Wei Lin,

*^e Han-Jia Lin,^b Anisha Anand,^b Binesh Unnikrishnan,^b Amit Nain^g and Chih-Ching Huang

*^bhi

Author affiliations

* Corresponding authors

^a Graduate Institute of Photonics, National Changhua University of Education, Changhua 50058, Taiwan

^b Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202301, Taiwan
E-mail: huanging@ntou.edu

^c Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada

^d Department of Pediatrics, Mackay Memorial Hospital and Mackay, Junior College of Medicine Nursing and Management, Taipei 10449, Taiwan

^e Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan
E-mail: antai@cc.ncue.edu.tw, linywjerry@cc.ncue.edu.tw

^f Nursing and Management, Mackay Junior College of Medicine, Taipei 11260, Taiwan

^g Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

^h Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202301, Taiwan

ⁱ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

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 μg 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.

Nanoscale

Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment

Social activity

Search articles by author

Spotlight

Advertisements