Enhancing Cell Nucleus Accumulation and DNA Cleavage Activity of Anti-Cancer Drug via Graphene Quantum Dots

Abstract

Graphene quantum dots (GQDs) maintain the intrinsic layered structural motif of graphene but with smaller lateral size and abundant periphery carboxylic groups, and are more compatible with biological system, thus are promising nanomaterials for therapeutic applications. Here we show that GQDs have a superb ability in drug delivery and anti-cancer activity boost without any pre-modification due to their unique structural properties. They could efficiently deliver doxorubicin (DOX) to the nucleus through DOX/GQD conjugates, because the conjugates assume different cellular and nuclear internalization pathways comparing to free DOX. Also, the conjugates could enhance DNA cleavage activity of DOX markedly. This enhancement combining with efficient nuclear delivery improved cytotoxicity of DOX dramatically. Furthermore, the DOX/GQD conjugates could also increase the nuclear uptake and cytotoxicity of DOX to drug-resistant cancer cells indicating that the conjugates may be capable to increase chemotherapy efficacy of anti-cancer drugs that are suboptimal due to the drug resistance.

Reduced graphene oxide–silver nanoparticle nanocomposite: a potential anticancer nanotherapy

“…18 A GOTiO 2 hybrid caused significant elevation in caspase-3 activity inducing apoptotic death; the hybrid showed excellent photodynamic anticancer activity without dark cytotoxicity. 19, 20 Hu et al 19 and Wang et al 20 demonstrated the dual functionality of graphene quantum dots as targeted anticancer drug carriers and DNA cleavage activity enhancers, which could be useful in cancer therapy. Transferrin-conjugated polyethylene glycolated GO was demonstrated as an efficient nanovector for the targeted delivery of anticancer drugs to brain tumors both in in vitro and in vivo conditions.…”

Improving cytotoxicity against cancer cells by chemo-photodynamic combined modalities using silver-graphene quantum dots nanocomposites

“…carbon nanomaterials, 10,[16][17][18][19][20][21][22] and magnetic nanoparticles 23,24 have been explored for theranostic applications. Graphene and graphene-based materials, ie, graphene oxide (GO) and graphene quantum dots (GQDs), have attracted interest in the biomedical field and have shown great potential for making a significant impact in cancer therapy and diagnosis.…”

“…10,[16][17][18][19][20][21][22][25][26][27][28][29][30] GQDs demonstrated excellent electrochemical and optical properties as well as the capability to bind with a variety of aromatic biomolecules through a π-π stacking interaction and/or electrostatic interaction, which make them ideal materials for loading chemotherapeutic drugs. 18,19,21,27,30 The use of GQDs to deliver doxorubicin (DOX), a chemotherapy drug, to cancer cells was reported, and the release of the anticancer drug was pH responsive. 19,30 Wang et al showed that GQDs delivered DOX to the nucleus of the cancer cells and enhanced the cytotoxicity of DOX dramatically.…”

“…19,30 Wang et al showed that GQDs delivered DOX to the nucleus of the cancer cells and enhanced the cytotoxicity of DOX dramatically. 18 They showed that GQDs do not release their cargo through a pH-triggering mechanism and postulated that DOX binds to the nuclear DNA after the diffusion of GQDs to the nucleus of the cell. Moreover, the use of GQDs in PDT was reported, with demonstrated cytotoxicity upon irradiation with visible light.…”

“…18 characterization of ag-gQDs/DOX nanoconjugates UV-Vis absorption and PL emission of the mixtures were recorded. The binding constant of DOX to Ag-GQDs was calculated by monitoring the quenching in the fluorescence of DOX according to a previously published method.…”