title: Folate-Mediated Targeted Delivery of Combination Chemotherapeutics Loaded Reduced Graphene Oxide for Synergistic Chemo-Photothermal Therapy of Cancers.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Hence, FA-P407-rGO/ID can be considered as a potential formulation for folate-targeted chemo-photothermal therapy in cancer cells.
authors: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea.
authors: Raj Kumar
authors: RK
authors: Thapa
authors: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea.
authors: Yongjoo
authors: Y
authors: Choi
authors: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea.
authors: Jee-Heon
authors: JH
authors: Jeong
authors: School of Pharmacy, SungKyunKwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, 440-746, South Korea.
authors: Yu Seok
authors: YS
authors: Youn
authors: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
authors: Han-Gon
authors: HG
authors: Choi
authors: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea. csyong@yu.ac.kr.
authors: Chul Soon
authors: CS
authors: Yong
authors: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, South Korea. jongohkim@yu.ac.kr.
authors: Jong Oh
authors: JO
authors: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival; D000077143:Docetaxel; D004337:Drug Carriers; D065546:Drug Liberation; D004357:Drug Synergism; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D006108:Graphite / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D000077146:Irinotecan; D061986:MCF-7 Cells; D053758:Nanoparticles; D010316:Particle Size; D010789:Phototherapy; D013499:Surface Properties; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D006108:Graphite; D005492:Folic Acid; D002166:Camptothecin
keywords: combination chemotherapy; docetaxel; folic acid; irinotecan; reduced graphene oxide