Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects

Every year, millions of people are impacted by bacterial infections, which are a significant global health concern due to the more recurring antibiotic-resistant bacterial strains [1]. To address this issue, antibacterial agents such as antibiotics, metal ions, and quaternary ammonium compounds are extensively utilized to inhibit bacterial growth and disrupt their structures [2]. However, the rising antibiotic resistance demands the urgent development of more efficient antibacterial agents. Among others, graphene quantum dots (GQDs) seem to be a promising candidate for antibacterial therapy [[3], [4], [5]].

As a new member of the carbon nanostructures material family, GQDs have funneled unprecedented attention because of their exceptional properties such as tunable photoluminescence [6,7], diverse possibilities for functionalization [8,9], photostability [10], biocompatibility [11], nontoxicity [12], high chemical inertness as well as long-term resistivity to photobleaching [13]. These zero-dimensional (0-D) nanostructures consist of single or few-atom-thick sheets of sp2 hybridized carbon atoms, with lateral dimensions below 100 nm [6]. GQDs properties are dependent on their size, making them highly adaptable for a wide range of applications. Thus, GQDs are investigated for their applications in a broad range of research fields, such as electronics [14], optoelectronics [15], biomedical imaging [16], drug delivery systems [17], catalysis [18], sensors [19], and others [20,21]. Compared to graphene, GQDs have distinct advantages such as tunable bandgap, dispersibility in polar organic solvents and water, photoluminescence, and various functional groups available for structural modification [22,23]. Due to low toxicity, and good dispersibility in water, GQDs are highly suitable for biomedical applications [[24], [25], [26]]. The photostability and tunable photoluminescence (PL) of these nanomaterials position them as highly effective bioimaging agents. To this extent, it has been widely reported the monitoring and visualization of the targeted delivery and release of anticancer drugs [17,27,28]. The PL properties of GQDs can be affected by the synthetic method, chemical composition, and surface passivation techniques [29].

In this study, the photo-induced antibacterial activity of S, N-doped GQDs was investigated. Gamma (γ) irradiation was selected to modulate GQD's structure due to the low consumption of chemicals needed for structural modification and avoidance of the use of aggressive chemical reagents for modification, as well as a time-saving approach [30]. Namely, in only one synthetic step, GQDs were doped using exclusively the L-cysteine amino acid as a source of heteroatoms. Furthermore, the reactive radicals formed during γ irradiation were quenched immediately after they were removed from the radiation source, avoiding the need for complex cleaning procedures and high-price storage of reactive residual reagents [31]. Our previous studies showed that both graphene and carbon quantum dots (CQDs) induce the death of bacterial cells when they are exposed to light [3,[32], [33], [34]]. A notable impact on the viability of Escherichia coli or Staphylococcus aureus was not observed when bacterial cells were exposed to the high GQDs concentration (200 μg/mL) alone or solely to blue light. However, when the bacteria were exposed to both GQDs (200 μg/mL) and light simultaneously, there was a significant reduction in their viability [3]. In another study, it was shown that N-doped CQDs displayed the most potent antibacterial activity against Enterobacter aerogenes, Proteus mirabilis, Staphylococcus saprophyticus, Listeria Monocytogenes, Salmonella typhimurium, Klebsiella pneumoniae compared to graphene oxide (GO), GQDs and CQDs [34]. Thus, γ irradiation was used as a tool to modulate GQDs structure, to achieve doping with S- and N-atoms, and improving the photoinduced antibacterial activity of GQDs. The interactions between GQDs and human serum albumin (HSA) were investigated as well. HSA investigations were developed considering that this is the most abundant transport protein in blood circulation [35]. Understanding HSA-drug interactions is important for pharmacokinetic and pharmacodynamic drug profiling. Furthermore, drug binding to HSA can be altered in certain diseased states. Thus, information about HSA-drug interactions can be a useful tool for establishing optimal therapy.

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