Quaternized carbon quantum dots with broad-spectrum antibacterial activity for treatment of wounds infected with mixed bacteria

Abstract

Quaternized carbon quantum dots (qCQDs) with broad-spectrum antibacterial activity were synthesized by a simple green “one-pot” method using dimethyl diallyl ammonium chloride and glucose as reaction precursors. The qCQDs showed satisfactory antibacterial activity against both gram-positive and gram-negative bacteria. In rat models of wounds infected with mixed bacteria, qCQDs obviously restored the weight of rats, significantly reduced the death of rats from severe infection, and promoted the recovery and healing of infected wounds. Biosafety tests confirmed that qCQDs had no obvious toxic and side effects during the testing stage. The analysis of quantitative proteomics revealed that qCQDs mainly acted on the ribosomal proteins of gram-positive bacteria and significantly down-regulated the metabolization-related proteins of gram-negative bacteria. Real-time quantitative PCR verified the expression levels of genes corresponding to the proteins with significant differences expressed by the two species of bacteria after treated with qCQDs. The variation trend of the detected genes was consistent with the results of proteomics, meaning that qCQDs played the antibacterial effect on bacteria with a new antibacterial mechanism.

Carbon Quantum Dots Derived from Different Carbon Sources for Antibacterial Applications

“…Little is known about the molecular mechanism of antibacterial activity once carbon quantum dots have gained intra-cellular access through cell wall damage. It is likely that carbon quantum dots affect gene expression [90].…”

“…Quaternized carbon quantum dots prepared from dimethyl diallyl ammonium chloride and glucose as precursors had MIC values between 12.5 µg/mL and 25 µg/mL for Gram-positive S. epidermidis, S. aureus, MRSA and E. faecalis, ranging up to 50 µg/mL for Gram-negative E. coli and P. aeruginosa (also see Table 2) [90]. Proteomic analyses suggested that the quaternized carbon quantum dots acted on ribosomal proteins in Gram-positive bacteria and downregulated metabolization-related proteins of Gram-negative bacteria.…”

“…In vivo studies are either performed with respect to evaluating antibacterial efficacies of carbon quantum dots or to establish their biosafety. Carbon is generally considered non-toxic, and quaternized carbon quantum dots, for instance, showed no obvious toxic side-effects during experimental treatment of infected wounds in rats [90] or pneumonia in mice [91]. Systematic evaluation of the biosafety of photoluminescent carbon quantum dots, synthesized through nitric acid oxidation, demonstrated no acute or sub-acute toxicity nor genotoxicity [101].…”

“…In vivo evaluation of the antibacterial efficacy of carbon quantum dots, so far, has pointed out that quaternized carbon quantum synthesized from organic sources were equally efficacious in treating infection in rodents as antibiotics. The application of quaternized carbon quantum dots to wounds infected by a combination of S. aureus and P. aeruginosa in rats was equally efficacious as treatment with levofloxacin [90]. Additionally, positively charged carbon quantum dots prepared by heating of polyethene polyamine could be used to treat wounds infected by a combination of S. aureus and E. coli, with an efficacy equal to levofloxacin [92].…”

“…Antibiotics 2021, 10, x FOR PEER REVIEW 16 of 22 quantum dots have gained intra-cellular access through cell wall damage. It is likely that carbon quantum dots affect gene expression[90]. Examples of the antibacterial activity of carbon quantum dots according to different antibacterial mechanisms and synergistic use with antibiotics: (A) Cell wall damage to E. coli and S. aureus, inflicted upon exposure to cationic carbon quantum dots, pyrolytically synthesized from spermidine.…”