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Folate-Mediated Targeted Delivery of Combination Chemotherapeutics Loaded Reduced Graphene Oxide for Synergistic Chemo-Photothermal Therapy of Cancers

Title
Folate-Mediated Targeted Delivery of Combination Chemotherapeutics Loaded Reduced Graphene Oxide for Synergistic Chemo-Photothermal Therapy of Cancers
Author
최한곤
Keywords
combination chemotherapy; docetaxel; folic acid; irinotecan; reduced graphene oxide; LIQUID-CRYSTALLINE NANOPARTICLES; AQUEOUS DISPERSIONS; ANTICANCER DRUGS; DOCETAXEL; NANOSHEETS; RECEPTOR; CELLS; NANOCARRIER; DIAGNOSIS
Issue Date
2016-10
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
PHARMACEUTICAL RESEARCH, v. 33, No. 11, Page. 2815-2827
Abstract
Purpose Larger surface area for drug incorporation and superior optical activity makes reduced graphene oxide (rGO) a suitable drug carrier for combination chemotherapeutics delivery. And folate receptors are potential mediators for cancer targeted delivery. This study mainly aimed to prepare irinotecan (IRI)- and docetaxel (DOC)-loaded, folate (FA)-conjugated rGO (FA-P407-rGO/ID) for synergistic cancer therapy. Methods FA-P407-rGO/ID was prepared as aqueous dispersion. Characterization was performed using high performance liquid chromatography (HPLC), transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet/visible spectroscopy, fourier transform infrared spectroscopy (FTIR) and drug release. In vitro cellular studies were performed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), fluorescence-activated cell sorting (FACS) and western blot analyses. Results Our results revealed successful preparation of stable FA-P407-rGO/ID formulation with enhanced drug release profiles in acidic microenvironment. In vitro cytotoxicity of the formulation on folate receptor-expressing human mammary carcinoma (MCF-7) cells was higher than that when free IRI/DOC combination (ID) was used; such increased cytotoxicity was not observed in folate receptor-negative hepatocellular carcinoma (HepG2) cells. Cellular uptake of FA-P407-rGO/ID in MCF-7 cells was higher than in HepG2 cells. Further, FACS and western blot analysis revealed better apoptotic effects of the formulation in MCF-7 cells than in HepG2 cells, suggesting the important role of folate receptors for targeted chemotherapy delivery to cancer cells. Near infrared irradiation further enhanced the apoptotic effect in cancer cells, resulting from the photothermal effects of rGO. Conclusions Hence, FA-P407-rGO/ID can be considered as a potential formulation for folate-targeted chemophotothermal therapy in cancer cells.
URI
https://link.springer.com/article/10.1007%2Fs11095-016-2007-0https://repository.hanyang.ac.kr/handle/20.500.11754/70374
ISSN
0724-8741; 1573-904X
DOI
10.1007/s11095-016-2007-0
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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