title: Synthesis and evaluation of glycopolymeric decorated gold nanoparticles functionalized with gold-triphenyl phosphine as anti-cancer agents.
abstract: In this study, statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated glyconanoparticles with the anticancer drug, gold(I) triphenylphosphine. These glyconanoparticles and the corresponding conjugates were then tested for their in vitro cytotoxicity in both normal and cancer cell lines using Neutral Red assay. The glyconanoparticles and their Au(I)PPh3 conjugates were all active against MCF7 and HepG2 cells, but galactose-functionalized glyconanoparticles {P(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP} were found to be the most cytotoxic to HepG2 cells (IC50 ∼ 4.13 ± 0.73 μg/mL). The p(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP was found to be a 4-fold more potent antitumor agent in HepG2 cells, and the overexpressed asialoglycoprotein (ASGPR) receptors revealed to play an important role in the cytotoxicity, presumably by the enhanced uptake. In addition, the glyconanoparticles Au(I) conjugates are found to be significantly more toxic as compared to the standard chemotherapeutic reagents such as cisplatin and cytarabine.
authors.affiliation: Department of Chemical and Materials Engineering and §Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB, Canada.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Adokoh
authors.forename: Stephen
authors.initials: S
authors.lastname: Quan
authors.forename: Mary
authors.initials: M
authors.lastname: Hitt
authors.forename: James
authors.initials: J
authors.lastname: Darkwa
authors.forename: Piyush
authors.initials: P
authors.lastname: Kumar
authors.forename: Ravin
authors.initials: R
authors.lastname: Narain
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D003561:Cytarabine / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D011108:Polymers; D003561:Cytarabine; C061896:triphenylphosphine; D006046:Gold; D002945:Cisplatin