title: Silver nanoparticle-embedded graphene oxide-methotrexate for targeted cancer treatment.
abstract: Combination therapies are widely investigated cancer treatment modalities. Carbon based systems such as graphene oxide (GO), plasmonic nanoparticles such as silver nanoparticles (AgNPs), and the folate analog, methotrexate (MTX), have been separately studied for their potential anticancer effects. In this study, we combined these systems to develop AgNPs-embedded GO with conjugated MTX (MTX-GO/AgNPs) and studied their folate receptor-targeted anticancer effects. Results revealed successful formation of AgNPs on GO along with MTX conjugation as suggested by UV/visible, TEM, AFM, FTIR, and XRD analysis. Folate receptor-positive MCF-7 cells were more prone to cytotoxic effects of MTX-GO/AgNPs compared to folate receptor-negative HepG2 cells. Folic acid analog MTX interacts with folate receptors expressed in MCF-7 cells, improving cellular uptake and subsequent anticancer effects of the system. Importantly, AgNPs enhanced the total ROS production within the treated cells leading to improve cellular apoptosis, as evidenced by western blot. Moreover, near infrared (NIR)-induced photothermal effects of GO improved the anticancer activity of the system. Therefore, the combinational therapy system MTX-GO/AgNPs can be potentially applied for effective folate receptor-targeted treatment of cancers.
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Thapa
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea.
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 330 Geumrak 1-ri, Hayang Eup, Gyeongsan, 38430, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Republic of Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea. Electronic address: csyong@ynu.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, 712-749, Republic of Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D058972:Folic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D058972:Folic Acid Transporters; D010087:Oxides; D017382:Reactive Oxygen Species; D012834:Silver; D006108:Graphite; D008727:Methotrexate
keywords: Combined chemotherapy; Graphene oxide; Methotrexate; Reactive oxygen species; Silver nanoparticles