Applications of Antimicrobial Carbon Dots: History
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Frequent bacterial/fungal infections and occurrence of antibiotic resistance pose increasing threats to the public and thus require the development of new antibacterial/antifungal agents and strategies. Carbon dots (CDs) have been well demonstrated to be promising and potent antimicrobial nanomaterials and serve as potential alternatives to conventional antibiotics.

  • antibacterial
  • bactericidal
  • disinfection
  • carbon nanodots
  • carbonized polymer dots

1. Introduction

Owing to the long-term use and overuse of antibiotics, pathogens have become resistant to almost all existing traditional antibiotics by mutating or acquiring drug-resistant genes from other organisms. It is urgently necessary to develop novel effective antimicrobial compounds as potent alternatives to the conventional small-molecule antibiotics to address the issue of microbial drug resistance. The great advancement of nanoscience and nanotechnology has offered a new solution for the development of antimicrobial materials. Several types of nanomaterials are known to exhibit antibacterial properties. Particularly, inorganic metal and metal oxide nanoparticles have been intensively investigated for their potential use as antimicrobial agents [1,2]. Although these metal (e.g., Au and Ag) and metal oxide (e.g., Fe2O3, CuO, and ZnO) nanoparticles possess antimicrobial activities, the release of metal ions may cause nonspecific biological toxicity, which urgently requires the development of safer antimicrobial nanomaterials [3,4]. Among the large variety of antimicrobial nanomaterials, carbon dots (CDs) have received ever-increasing attention, mainly due to their easy preparation and functionalization, great water dispersity, and satisfactory biocompatibility. One appealing merit for CDs is that their property and function can be easily manipulated during the synthesis or post-modification stage, which is highly useful for antibacterial applications. CDs are zero-dimensional carbonaceous nanoparticles with sizes no more than 20 nm, also termed “carbonized polymer dots”, “carbon quantum dots”, or “carbon nanodots” [5,6,7,8,9,10,11]. CDs can be prepared from a wide variety of natural materials such as biomass and waste, and a huge array of chemical agents [12,13]. There are two well-known CD preparation strategies: bottom-up strategy and top-down strategy. The synthetic approaches for CDs include hydrothermal/solvothermal reaction, pyrolysis, sonication, microwave irradiation, etc. [12]. The broad applications of CDs in sensing [12,14,15,16], optoelectronics [17], energy [18], catalysis [12,19], and nanomedicine [20,21,22,23,24], have been demonstrated since their discovery in 2004 [25].
Currently, three antimicrobial mechanisms have been reported for CDs, including cell wall/membrane disruption, reactive oxygen species (ROS) generation, and DNA damage [23]. The inhibitory action of CDs on microorganisms depends on the composition, size, shape, and surface chemistry of CDs. It is extremely difficult to explain the antimicrobial mechanisms of CDs without performing careful structural characterizations of the CDs. Specifically, the catalytic activity, the crystallographic structure, the surface state (defect or functionalization), and charge transfer are important factors that contribute to the antimicrobial activity of CDs. However, currently, except for the several studies that mentioned the effect of surface functionalization on the antimicrobial activity of CDs [7,24,26], detailed evaluations of the other factors are still lacking in the current CD-based antimicrobial studies. As a result, more attention should be paid to the investigations of the effect of the other factors on the antimicrobial activity of CDs in the future.

2. Applications of Antimicrobial CDs in Medical and Industry Fields

CDs-involved antimicrobial strategies have been deployed in both medical and industry fields. In the medical field, antimicrobial CDs have been leveraged for coating the surface of orthopedic implant materials [66], delivering drugs [24,57,103,104], and repairing infected bone defects [47]. Moradlou et al. grew a thin film of CDs-incorporated hematite (CQDs@α-Fe2O3) on a titanium substrate to yield Ti/CQDs@α-Fe2O3 [66]. CQDs were prepared from graphite rods via an electrochemical method and used as nano-scaffolds for the growth of CQD@α-Fe2O3 nanoparticles as core@shell nanostructures. The Ti/CQDs@α-Fe2O3 samples exhibited sustainable antibacterial activity against S. aureus but not E. coli, offering a way of using CDs to prepare antimicrobial materials for medical devices. In another work, Geng et al. synthesized positively-charged CQDs (p-CQDs) through microwave reaction of spermidine trihydrochloride, and prepared negatively-charged CQDs (n-CQDs) via microwave reaction of 1,3,6-trinitropyrene (TNP) and sodium sulfite [47]. The p-CQDs displayed effective antibacterial activity against multidrug-resistant (MDR) bacteria and could realize the inhibition of biofilm formation, while n-CQDs notably promoted bone regeneration. The nearly neutral p-CQD/WS2 hybrids were first fabricated by depositing p-CQDs on WS2 nanosheets, and then coencapsulated with n-CQDs into the gelatin/methacrylate anhydride (GelMA) hydrogel to obtain p-CQD/WS2/n-CQD/GelMA hydrogel scaffold. The implantation of p-CQD/WS2/n-CQD/GelMA hydrogel scaffold in an MRSA-infected craniotomy defect model induced almost complete repair of an infected bone defect with the new bone area of 97.0 ± 1.6% at 60 days. This work proposes a CD-based strategy for developing biomaterials with both antibacterial and osteogenic activities for the treatment of infected bone defects.
In the industry field, antimicrobial CDs have been utilized to construct thin-film composite membranes for forward osmosis [105] and nanofiller [106], packaging materials [107,108], and lubricant additives [53]. Mahat et al. developed thin-film composite membranes for forward osmosis by embedding CQDs derived from oil palm biomass into polysulfone-selective layers, which were denoted as CQDs-PSF (PSF: polysulfone) [105]. The authors proved that the addition of CQDs into PSF membranes increased water flux and improved antibacterial performance. In another study, Koulivand et al. constructed antifouling and antibacterial nanofiltration membranes for efficient salt and dye rejection by incorporating nitrogen-doped CDs (NCDs) to polyethersulfone (PES) using a phase inversion technique [106]. The antibacterial NCDs were synthesized via hydrothermal treatment of ammonium citrate dibasic. The obtained membrane exhibited improved pure water flux and enhanced antifouling property. In addition, Kousheh et al. constructed a nanocellulose film with antimicrobial/antioxidant and ultraviolet (UV) protective activities for food packaging by introducing water-dispersible and photoluminescent CDs [107]. The antimicrobial CDs were synthesized from cell-free supernatant of Lactobacillus acidophilus via a hydrothermal method. The as-synthesized CDs were embedded into bacterial nanocellulose (BNC) film due to the hydrogen bonding interaction between CDs and the carboxyl, hydroxyl, and carbonyl groups of BNC, leading to the formation of the CD-BNC film. The CD-BNC film displayed a higher inhibitory activity toward Listeria monocytogenes than E. coli. In addition to antibacterial activity, the introduction of CDs into the BNC film also endowed the CD-BNC film with UV-blocking activity, fluorescence appearance, and improved flexibility. The CD-BNC film could be used to fabricate nanopaper for wrapping of food commodity and fabrication of forgery-proof packaging. In addition to thin-film composite membranes and packaging materials, antimicrobial CDs have been implemented as lubricant additives. Tang et al. fabricated CDs from PEG and PEI through a hydrothermal approach [53]. The MICs of the CDs toward E. coli and S. aureus were 62.5 and 15.56 μg mL−1, respectively. Besides the antibacterial activity, the CDs featured anti-friction property. The addition of 0.2% (wt) CDs reduced the mean friction coefficient and wear volume of water-based lubrication by 59.77% and 57.97%, respectively. This example suggests that CDs with antibacterial and anti-friction functions can be utilized as an advanced lubricating additive, thus broadening the practical application of CDs.

This entry is adapted from the peer-reviewed paper 10.3390/ph15101236

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