Novel Carbon Quantum Dots Precisely Trigger Ferroptosis in Cancer Cells through Antioxidant Inhibition Synergistic

Nianqiang Jin1,2, Zilin Wang3, Chengcheng Yin4,5

  • 1Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, People's Republic of China.

Insights

Novel carbon quantum dots derived from gentamycin (GM-CQDs) effectively lower glutathione (GSH) levels in tumors. This strategy enhances reactive oxygen species (ROS) therapy efficacy and shows promising antitumor activity with good safety.

Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Oncology

Background:

  • High glutathione (GSH) levels in malignant tumors contribute to treatment resistance and ineffective reactive oxygen species (ROS) therapy.
  • GSH's potent ROS scavenging ability significantly diminishes the therapeutic potential of ROS-based cancer treatments.

Purpose of the Study:

  • To develop novel carbon quantum dots (CQDs) targeting GSH to overcome treatment resistance in malignant tumors.
  • To investigate the mechanism of action of gentamycin-derived CQDs (GM-CQDs) in reducing intracellular GSH and inducing tumor cell death.

Main Methods:

  • Synthesis of novel carbon quantum dots from gentamycin (GM-CQDs).
  • Assessment of GM-CQDs' effect on intracellular GSH levels, redox balance, and ferroptosis induction.
  • Transcriptome analysis to elucidate the molecular mechanisms of GM-CQDs.
  • In vivo studies to evaluate antitumor activity and immune activation.

Main Results:

  • GM-CQDs were synthesized, characterized by sp2/sp3 carbon atoms and nitrogen-oxygen groups.
  • GM-CQDs effectively decreased intracellular GSH by downregulating SLC7A11, disrupting redox balance, and inducing ferroptosis.
  • Transcriptome analysis confirmed downregulation of GSH metabolism and upregulation of ferroptosis-related pathways.
  • In vivo studies demonstrated significant antitumor activity, immune activation, and ideal biological safety.

Conclusions:

  • GM-CQDs represent a novel therapeutic strategy for targeting GSH in malignant tumors.
  • GM-CQDs effectively induce ferroptosis and exhibit potent antitumor effects with good safety profiles.
  • These findings highlight the potential of GM-CQDs for overcoming drug resistance and enhancing cancer therapy.