Hydroxylated-graphene quantum dots induce cells senescence in both p53-dependent and -independent manner

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Graphene quantum dots (GQDs) possess unique properties making them promising for biomedical applications like drug delivery, bioimaging, and photodynamic therapy (PDT).
• Hydroxyl modification of GQDs (OH-GQDs) may alter their interaction with biological systems, necessitating investigation into their specific effects on cancer cells.

Purpose of the Study:

• To investigate the effects of hydroxyl-modified graphene quantum dots (OH-GQDs) on lung carcinoma cell lines A549 (wild type p53) and H1299 (p53-null).
• To elucidate the mechanisms underlying the cytotoxic effects of OH-GQDs, including their role in reactive oxygen species (ROS) generation and cell cycle regulation.

Main Methods:

• Treatment of A549 and H1299 cells with varying concentrations of OH-GQDs.
• Assessment of cell viability using standard assays.
• Measurement of intracellular reactive oxygen species (ROS) generation.
• Evaluation of cell cycle distribution (G0-G1 arrest) and senescence.
• Analysis of key signaling pathway components, including p21 and phosphorylated Rb.

Main Results:

• A medium concentration (50 μg mL⁻¹) of OH-GQDs significantly reduced the viability of both A549 and H1299 lung cancer cells.
• OH-GQDs treatment led to enhanced intracellular ROS generation, which was partially mitigated by the ROS scavenger N-acetylcysteine (NAC).
• OH-GQDs induced G0-G1 cell cycle arrest and cellular senescence, activating p21 expression in a p53-dependent and -independent manner, and inhibiting Rb phosphorylation.

Conclusions:

• Hydroxyl-modified graphene quantum dots exhibit significant cytotoxicity towards lung carcinoma cells through ROS generation and cell cycle arrest.
• The observed effects on p21 and Rb phosphorylation suggest a complex signaling pathway modulation by OH-GQDs.
• These findings highlight the potential of OH-GQDs for biomedical applications, particularly in cancer therapy, and provide crucial data for future GQD development.