Graphene Quantum Dots Downregulate Multiple Multidrug-Resistant Genes via Interacting with Their C-Rich Promoters

Chao Luo, Yanfang Li, Lijuan Guo, Fangwei Zhang, Hui Liu, Jiali Zhang, Jing Zheng, Jingyan Zhang, Shouwu Guo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Multidrug resistance (MDR) is the major factor in the failure of many forms of chemotherapy, mostly due to the increased efflux of anticancer drugs that mediated by ATP-binding cassette (ABC) transporters. Therefore, inhibiting ABC transporters is one of effective methods of overcoming MDR. However, high enrichment of ABC transporters in cells and their broad substrate spectra made to circumvent MDR are almost insurmountable by a single specific ABC transporter inhibitor. Here, this study demonstrates that graphene quantum dots (GQDs) could downregulate the expressions of P-glycoprotein, multidrug resistance protein MRP1, and breast cancer resistance protein genes via interacting with C-rich regions of their promoters. This is the first example that a single reagent could suppress multiple MDR genes, suggesting that it will be possible to target multiple ABC transporters simultaneously with a single reagent. The inhibitory ability of the GQDs to these drug-resistant genes is validated further by reversing the doxorubicin resistance of MCF-7/ADR cells. Notably, GQDs have superb chemical and physical properties, unique structure, low toxicity, and high biocompatibility; hence, their capability of inhibiting multiple drug-resistant genes holds great potential in cancer therapy.

Original languageEnglish (US)
Article number1700328
JournalAdvanced Healthcare Materials
Volume6
Issue number21
DOIs
StatePublished - Nov 8 2017
Externally publishedYes

Keywords

  • ABC transporters
  • gene regulation
  • graphene quantum dots
  • multidrug resistance

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