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

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.

Directed Graphene‐Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance

“…It is reported that pretreatment of cells with graphene quantum dots downregulates multidrug‐resistant genes and improves the chemotherapeutic efficiency intrinsically . However, the toxicities of GPD D and GPTD D without laser irradiation was low and a strong MDR effect was observed (Figure C).…”

Directed Graphene‐Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance

“…It is reported that pretreatment of cells with graphene quantum dots downregulates multidrug-resistant genes and improves the chemotherapeutic efficiency intrinsically. [12] However,t he toxicities of GPD D and GPTD D without laser irradiation was low and as trong MDR effect was observed ( Figure 3C). Ther easons for such different results can be different surface coatings,c oncentrations,a nd sizes of graphene derivatives as well as incubation times between our experiments and the reported work.…”

The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

“…Graphene quantum dots have exceptional physicochemical properties, good biocompatibility, low cytotoxic activity and emit intrinsic fluorescent light [53]. In addition to these properties, it was recently found [64] that a preincubation with GQDs can inhibit P-gp in MCF-7/ADR cell line-which overexpress this ABC transporter-via alternation modulation of the integrity and permeability of the cell membrane or depleting ATP pools. In addition, GQDs seems to be downregulating the P-gp (MDR1), MRP1 and BCRP genes of every cell line investigated in that study via interaction with their C-rich promoter region.…”