Conjugated carbon quantum dots: Potent nano-antibiotic for intracellular pathogens

A common theme in the persistence of microbial infections involves intracellular survival of microbial pathogens within host cells where they stay sheltered from attack by antimicrobial agents. In order to improve antimicrobial access inside host cells, we developed nanoparticles intracellular delivery of antibiotics. Using an intracellular infection model with the periodontal pathogen, Porphyromonas gingivalis (P. gingivalis), we demonstrated significantly enhanced intracellular microbicidal activity with the standard antibiotic metronidazole (MET) through its conjugation onto 1-5 nm biocompatible nano-carrier, carbon quantum dot, which was derived from chlorophyll (cCQD). The conjugated cCQD-MET were rapidly internalized into the cultured cells, reaching almost 90% uptake within 3 h of the challenge. Our results consistently showed enhanced antimicrobial activity of the conjugate compared to MET alone. Even at concentrations as low as 0.26 µM, the conjugate showed 72% enhancement compared to the drug alone, resulting in significantly increased inhibition of intracellular P. gingivalis at lower antibiotic dosages. We achieved a high drug payload (80% w/w) on cCQD without affecting the potency of metronidazole as determined by cytotoxicity assays, cellular uptake of metronidazole, P. gingivalis invasion and elimination assays. The synthesized cCQD also displayed high fluorescence with 56% quantum yield at an absorbance peak of 380 nm and an emission peak of 480 nm, thus, allowing for fluorescence tracking and quantification of the drug intracellularly. A similar strategy may be used to repurpose other antibiotics for the treatment of intracellular bacterial infections.