Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition.

Autor: Su Y; Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China., Ye K; Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China., Hu J; School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China., Zhang Z; School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China., Wang Y; Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China., Geng B; School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China., Pan D; School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China., Shen L; Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.; Department of Orthopedic Surgery, Sheyang County People's Hospital, Yancheng, Jiangsu, 224300, China.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Jul; Vol. 13 (19), pp. e2304648. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1002/adhm.202304648
Abstrakt: 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 (IC 50 )) 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.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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