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( Tuan Hiep Tran ),( Hanh Thuy Nguyeon ),( Tung Thanh Pham ),( Ju Yeon Choi ),( Han Gon Choi ),( Chul Soon Yong ),( Jong Oh Kim ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
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-Dl) 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.
( Tuan Hiep Tran ),( Tuan Duc Nguyen ),( Bijay Kumar Poudel ),( Hanh Thuy Nguyeon ),( Jong Oh Kim ),( Chul Soon Yong ),( Chien Ngoc Nguyen ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Artesunate (ART)-a well-known hydrophobic anti-malarial agent was incorporated in a polymer-lipid hybrid nanocolloidal system for anti-cancer therapeulic, The lipid negatively charged nanocmulsion was formulated by modified hot homogenization method then covered with positively charged chitosan via clectroslatic interaction to obtain chitosan-coated lipid nanocapsule (ART-CLN). Physical properties of the system were characterized in terms of size, charge morphology, drug loading capacity, and physicca stale, In addition, anti-cancer activities were confirmed by conductiong MTT assay for ART and ART-CLN, on different cancer cell lines. Obtained ART_CLN after coating chilosan revelated positive charge (13.2±0.87 mV), small particle size (160.9±3.5 nm), and spherical shape. High drug entrapment cfficiency (95.49±1.13%) and sustaubed rekease pattern were obscrved. Moreover, the good cellular uptake was recorded by flow cytomctry as well as confocal image. Finally, ART-CLN Exhibited stronger anti-cancer activity than free ART on breast cancer cell lines (MCF-7, MDA-MB-231). These results suggested that by lading ART into lipid core of polymer lipid hybrid carrier, the activity and physical stability of ART can be significantly increased for cancer chemotherapy.