title: 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.
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Tuan Hiep
authors.initials: TH
authors.lastname: Tran
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Hanh Thuy
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Tung Thanh
authors.initials: TT
authors.lastname: Pham
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Hanyang University , 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University , 214-1 Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D010087:Oxides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010087:Oxides; D006108:Graphite; D004317:Doxorubicin
keywords: NIR; combination chemotherapy; doxorubicin; drug resistance; graphene oxide; irinotecan; poloxamer 188