RESUMEN
Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.
Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Grafito/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Puntos Cuánticos/química , Animales , Antibacterianos/química , Células Cultivadas , Escherichia coli/metabolismo , Infecciones por Escherichia coli/tratamiento farmacológico , Grafito/química , Humanos , Luz , Staphylococcus aureus Resistente a Meticilina/metabolismo , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. Here we show that electrochemically produced GQD irradiated with blue light (470 nm, 1W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation, DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LC3B protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity.