Graphene quantum dots as autophagy-inducing photodynamic agents.
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.
Vinca Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia. zormark@vinca.rs
Zoran M
ZM
Markovic
Biljana Z
BZ
Ristic
Katarina M
KM
Arsikin
Djordje G
DG
Klisic
Ljubica M
LM
Harhaji-Trajkovic
Biljana M
BM
Todorovic-Markovic
Dejan P
DP
Kepic
Tamara K
TK
Kravic-Stevovic
Svetlana P
SP
Jovanovic
Marina M
MM
Milenkovic
Dusan D
DD
Milivojevic
Vladimir Z
VZ
Bumbasirevic
Miroslav D
MD
Dramicanin
Vladimir S
VS
Trajkovic
D017209:Apoptosis; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D004789:Enzyme Activation; D005434:Flow Cytometry / Q000379:methods; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D049449:Luminescence; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D017319:Photosensitizing Agents / Q000494:pharmacology*; D045663:Quantum Dots; D034622:RNA Interference; D013997:Time Factors
D017319:Photosensitizing Agents; D006108:Graphite; D020169:Caspases; D010100:Oxygen