title: Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro.
abstract: MicroRNAs have been demonstrated to be deregulated in different types of cancer. miR-21 is a key player in the majority of cancers. Down-regulation of miR-21 in glioblastoma cells leads to repression of cell growth, increased cellular apoptosis and cell-cycle arrest, which can theoretically enhance the chemotherapeutic effect in cancer therapy. In this study, the poly(amidoamine) (PAMAM) dendrimer was employed as a carrier to co-deliver antisense-miR-21 oligonucleotide (as-miR-21) and 5-fluorouracil (5-FU) to achieve delivery of as-miR-21 to human glioblastoma cells and enhance the cytotoxicity of 5-FU antisense therapy. The inhibitory effect toward brain tumors was evaluated by MTT assay, and measurements of cell apoptosis and invasion using the human brain glioma cell line U251. PAMAM could be simultaneously loaded with 5-FU and as-miR-21, forming a complex smaller than 100 nm in diameter. Both the chemotherapeutant and as-miR-21 could be efficiently introduced into tumor cells. The co-delivery of as-miR-21 significantly improved the cytotoxicity of 5-FU and dramatically increased the apoptosis of U251 cells, while the migration ability of the tumor cells was decreased. These results suggest that our co-delivery system may have important clinical applications in the treatment of miR-21-overexpressing glioblastoma.
authors.affiliation: School of Materials Science & Engineering, Tianjin University, Tianjin 300072, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
authors.forename: Xu-Bo
authors.initials: XB
authors.lastname: Yuan
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Guang Xiu
authors.initials: GX
authors.lastname: Wang
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Jia
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhong
authors.forename: Shizhu
authors.initials: S
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Sheng
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Pu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D050091:Dendrimers / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
chemical_list: D000964:Antimetabolites, Antineoplastic; D050091:Dendrimers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C104700:PAMAM Starburst; D005472:Fluorouracil