Development of a Graphene Oxide Nanocarrier for Dual-Drug Chemo-phototherapy to Overcome Drug Resistance in Cancer

Abstract

Despite tremendous progress in chemotherapy, drug resistance remains a major challenge for anticancer treatment. The combinations of chemo-photothermal and chemo-chemo treatments have been reported to be potential solutions to overcome drug resistance. In this study, we developed a dual-in-dual synergistic therapy based on the use of dual anticancer drug-loaded graphene oxide (GO) stabilized with poloxamer 188 for generating heat and delivering drugs to kill cancer cells under near-infrared (NIR) laser irradiation. The nanocomparable system is stable and uniform in size, generating sufficient heat to induce cell death. Dual drugs (doxorubicin and irinotecan)-loaded GO (GO-DI) in combination with laser irradiation caused higher cytotoxicity than that caused by the administration of a free single drug as well as a combination of drugs and blank GO in various cancer cells, especially in MDA-MB-231 resistant breast cancer cells. Exposure to "hot" NIR and GO-DI activated the intrinsic apoptosis pathway, which was confirmed based on changes in the morphology of cell nuclei and overexpression of apoptosis-related proteins. On the basis of the results, the combined treatment showed a synergistic effect compared to the effect of chemotherapy or photothermal treatment alone, demonstrating higher therapeutic efficacy to overcome one of the most severe problem in anticancer therapy, that of intrinsic resistance to chemotherapeutics.

Nanoparticle-based combination drug delivery systems for synergistic cancer treatment

“…For example, graphene oxide (Tran et al 2015), oil nanoemulsions (Ganta and Amiji 2009), and iron oxide nanoparticles (Dilnawaz et al 2010) are used for combination chemotherapy for various cancers. Graphene oxide possesses several peculiar characteristics that favor chemotherapeutic drug delivery to cancer cells, including a large surface area for drug incorporation and high drug loading based on p-p interactions with graphene sheets (Thapa et al 2016).…”

“…Graphene oxide possesses several peculiar characteristics that favor chemotherapeutic drug delivery to cancer cells, including a large surface area for drug incorporation and high drug loading based on p-p interactions with graphene sheets (Thapa et al 2016). Tran et al (2015) successfully loaded doxorubicin and irinotecan on nano-graphene oxides. An in vitro evaluation using different breast cancer cell lines suggested successful drug delivery to cancer cells.…”

Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration

“…Co., Eatontown, NJ) Sadahiro et al, 2015;Tran et al, 2015;Poudel et al, 2016). However, like other anticancer drugs, this drug produces severe cytotoxic side effects, such as body weight loss, irritation and diarrhea, owing to very high plasma concentrations.…”

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway

“…61 When the size of a GO molecule is too small, this may affect drug loading and the drug may be easily phagocytosed. 62 When the size of a GO molecule is too large, this may influence drug transport in the body. 63 The size of GO molecule investigated in this research did not affect drug loading and drug transport.…”