Cytocompatible Amphipathic Carbon Quantum Dots as Potent Membrane-Active Antibacterial Agents with Low Drug Resistance and Effective Inhibition of Biofilm Formation

Abstract

It is very challenging to design nanomaterials with both excellent antibacterial activity and cytocompatibility when facing bacterial infection. Here, inspired by antimicrobial peptides (AMPs), we fabricate carbon quantum dots (CQDs) derived from hydrophobic tryptophan and hydrophilic lysine or arginine (Lys/ Trp-CQDs and Arg/Trp-CQDs), which possess amphipathic properties. These CQDs could effectively destroy bacterial membranes without developing resistance, inhibit biofilms formed by Staphylococcus aureus, and exhibit good in vitro biocompatibility. The antibacterial activities are caused by not only surface cationic structures and excess intracellular reactive oxygen species (ROS) generated by the CQDs but also the effects of the surface hydrophobic groups. These combined mechanisms of actions lead to bacterial membrane disruption, which raises the hope for combating bacterial infection without concern about drug resistance. What's more, the effect of amphiphilicity on balancing sterilization with biocompatibility expands the research ideas for developing available antibacterial nanomaterials.

Chitosan-Based Hydrogel-Incorporated Trp-CDs with Antibacterial Properties and pH-Mediated Fluorescence Response as a Smart Food Preservation Material

“…The antibacterial activity of Trp-CDs increased as the pH was reduced from 7.4 to 4.0 (Figure B), which might be partially due to the increased ζ potential of the surface of Trp-CDs under acidic conditions. Additionally, more positive charges might accelerate the contact process between the ultrasmall Trp-CDs and the bacterial cell membrane, , which could disrupt the structural integrity of the cell membrane and eventually lead to cytoplasmic leakage (Figure C). It was further confirmed that the surface charge of Trp-CDs played a vital role in determining their antibacterial potency.…”

Synthesis, properties and mechanism of carbon dots-based nano-antibacterial materials

“…Therefore, they proposed that CDs are not only an excellent electron donor (D), but also an excellent electron acceptor (A), which can transfer electrons with other A or D molecules [89]. Subsequently, numerous studies confirmed this conclusion [72,73].…”

“…Based on the pyrolysis treatment of hydrophobic tryptophan and hydrophilic lysine or arginine, Li et al, developed amphipathic CDs using a simple method. These CDs destroy the bacterial membrane and rapidly kill bacteria via electrostatic interactions of cationic residues and the fusion of hydrophobic groups [73]. The amphiphilic CDs that were hydrothermally synthesized by Shaikh et al, using citrus as a raw material also inhibited bacterial adhesion and biofilm formation, while demonstrating a profound antibacterial activity [74].…”

Carbon Dots for Killing Microorganisms: An Update since 2019

“…Several CDs prepared from amino acids such as arginine [ 41 ], alanine [ 42 , 43 ], L-tryptophan [ 58 , 59 ], cysteine [ 43 , 44 ], lysine [ 59 ], and arginine [ 59 ] have been reported to possess antimicrobial activities. Suner et al synthesized nitrogen-doped arginine CDs (termed Arg CDs) utilizing citric acid as the carbon source and arginine as the amine source by a microwave-mediated approach ( Figure 2 B) [ 41 ].…”