Raj Kumar Thapa1, Yongjoo Choi1, Jee-Heon Jeong1, Yu Seok Youn2, Han-Gon Choi3, Chul Soon Yong4, Jong Oh Kim5. 1. College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea. 2. School of Pharmacy, SungKyunKwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, 440-746, South Korea. 3. College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea. 4. College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea. csyong@yu.ac.kr. 5. College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea. jongohkim@yu.ac.kr.
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 chemo-photothermal therapy in cancer cells.
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 chemo-photothermal therapy in cancer cells.
Authors: Lena A L Tang; Wong Cheng Lee; Hui Shi; Ethel Y L Wong; Anton Sadovoy; Sergey Gorelik; Jonathan Hobley; Chwee Teck Lim; Kian Ping Loh Journal: Small Date: 2011-12-13 Impact factor: 13.281