Co-delivery of as-miR-21 and 5-FU by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro.
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.
Ren
Yu
Y
School of Materials Science & Engineering, Tianjin University, Tianjin 300072, P.R. China.
Kang
Chun-Sheng
CS
Yuan
Xu-Bo
XB
Zhou
Xuan
X
Xu
Peng
P
Han
Lei
L
Wang
Guang Xiu
GX
Jia
Zhifan
Z
Zhong
Yue
Y
Yu
Shizhu
S
Sheng
Jing
J
Pu
Pei-Yu
PY
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
D000964:Antimetabolites, Antineoplastic; D050091:Dendrimers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C104700:PAMAM Starburst; D005472:Fluorouracil