Carboxylated graphene quantum dots as a nano-delivery system for insoluble curcumin in antimicrobial photodynamic therapy

Curcumin, a natural polyphenolic pigment, has gained significant attention due to its potent antimicrobial properties. However, its applications are limited by poor solubility and bioavailability. Conjugation with an appropriate nanocarrier can enhancing curcumin's therapeutic efficacy. Carboxylated graphene quantum dots (cGQDs) were chosen as the nanocarrier. cGQDs were functionalized with polyethylene glycol (PEG) and curcumin, resulting in the cGQDs-PEG-curcumin nanocomposite. The antimicrobial photodynamic therapy (aPDT) efficacy of the cGQDs-PEG-curcumin was evaluated against both Gram-positive and Gram-negative bacterial strains, including resistant variants. The cGQDs-PEG-curcumin nanocomposite demonstrated significant antimicrobial efficacy under light activation, particularly against Gram-positive bacterial strains, including resistant ones (Staphylococcus aureus MIC 3.5 µM, MBC 15 µM, Enterococcus faecalis MIC 0.94 µM, MBC 3.75 µM). It also has an effect on Gram-negative bacterial strains (Escherichia coli MIC 30 µM, MBC -). Among resistant strains, the highest efficacy was observed against vancomycin-resistant Enterococcus faecium (MIC 3.75 µM and MBC 3.75 µM) and rez. P. aeruginosa (MIC 15 µM and MBC 30 µM) upon irradiation at 5 J/cm². When double irradiation (2 ×5 J/cm²) was applied, both MIC and MBC values decreased for all tested Gram-positive bacterial strains. Binding curcumin to GQDs overcame the biological barrier posed by its poor water solubility. The synthesized nanocomposite accumulated in the bacterial cell wall, and upon light activation, induced rapid bacterial cell death immediately after irradiation, remarkably without generating reactive oxygen species (ROS). Overall, the cGQDs-PEG-curcumin nanocomposite, as a novel third-generation photosensitizer, demonstrates significant potential for aPDT, with a promising ability to overcome bacterial resistance.