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Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition
1Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Abstract:
Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG-targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half-maximal inhibitory concentration (IC50)) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC-mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG-targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano-bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.
Insights
Bioactive graphene quantum dots (GQDs) target cancer stem cells (CSCs) by inserting into DNA major grooves, eradicating drug-resistant cells and preventing metastasis. This novel nano-bio interface approach also reverses multidrug resistance.
Area of Science:
- Nanotechnology in oncology
- Cancer stem cell biology
- Drug resistance mechanisms
Background:
- Cancer stem cells (CSCs) drive metastasis and relapse, but are resistant to conventional chemotherapy.
- Current chemotherapeutics have limited efficacy against drug-resistant CSCs due to insufficient interfacial inhibition.
- Targeting the DNA major groove (MAG) offers a potential strategy for enhanced anti-cancer effects.
Purpose of the Study:
- To investigate the potential of graphene quantum dots (GQDs) for enhanced interfacial inhibition of CSCs.
- To explore the mechanism of GQD self-insertion into DNA MAG sites for cancer therapy.
- To evaluate the efficacy of MAG-targeted GQDs in reversing multidrug resistance (MDR) and blocking cancer metastasis.
Main Methods:
- Bioactive graphene quantum dots (GQDs) were designed for self-insertion into DNA major groove (MAG) sites.
- The effect of MAG-targeted GQDs on the expression of cancer stem genes (e.g., ALDH1, Notch1, Bmi1) was analyzed.
- GQD efficacy as a multidrug resistance (MDR) reverser was assessed at nontoxic concentrations, and their impact on cancer cell migration, invasion, and metastasis was evaluated.
Main Results:
- Self-insertion of GQDs into DNA MAG sites induced enhanced interfacial inhibition, leading to the eradication of drug-resistant CSCs.
- MAG-targeted GQDs effectively downregulated key cancer stem genes and reversed MDR by inhibiting MDR1 gene expression.
- GQDs substantially blocked CSC-mediated cancer cell migration, invasion, and metastasis, demonstrating significant anti-metastatic potential.
Conclusions:
- Enhanced nano-bio interface interactions at the DNA MAG site are crucial for eradicating CSCs.
- MAG-targeted GQDs offer a promising strategy for preventing cancer metastasis and recurrence by targeting CSCs and reversing MDR.
- GQDs can sensitize cancer cells to conventional chemotherapeutics, paving the way for improved combination chemotherapy regimens.
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