Open AccessCo‐delivery of micro RNA ‐21 antisense oligonucleotides and gemcitabine using nanomedicine for pancreatic cancer therapy
Author(s) -
Li Yaqing,
Chen Yinting,
Li Jiajia,
Zhang Zuoquan,
Huang Chumei,
Lian Guoda,
Yang Kege,
Chen Shaojie,
Lin Ying,
Wang Lingyun,
Huang Kaihong,
Zeng Linjuan
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13267
Subject(s) - pancreatic cancer , cancer research , downregulation and upregulation , metastasis , gemcitabine , gene silencing , polyethylenimine , chemistry , growth inhibition , cancer , apoptosis , biology , medicine , transfection , biochemistry , gene
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining downregulation of target genes with chemotherapy drugs, is expected to improve therapeutic effects. Therefore, we developed a combined therapy of micro RNA ‐21 antisense oligonucleotides ( ASO ‐miR‐21) and gemcitabine (Gem) using a targeted co‐delivery nanoparticle ( NP ) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth. Polyethylene glycol–polyethylenimine–magnetic iron oxide NP s were used to co‐deliver ASO ‐miR‐21 and Gem. An anti‐ CD 44v6 single‐chain variable fragment (scFv CD 44v6 ) was used to coat the particles to obtain active and targeted delivery. Our results showed that the downregulation of the oncogenic miR‐21 by ASO resulted in upregulation of the tumor‐suppressor genes PDCD 4 and PTEN and the suppression of epithelial–mesenchymal transition, which inhibited the proliferation and induced the clonal formation, migration, and invasion of pancreatic cancer cells in vitro . The co‐delivery of ASO ‐miR‐21 and Gem induced more cell apoptosis and inhibited the growth of pancreatic cancer cells to a greater extent than single ASO ‐miR‐21 or Gem treatment in vitro . In animal tests, more scFv CD 44v6 ‐ PEG ‐polyethylenimine/ ASO ‐magnetic iron oxide NP /Gem accumulated at the tumor site than non‐targeted NP s and induced a potent inhibition of tumor proliferation and metastasis. Magnetic resonance imaging was used to observed tumor homing of NP s. These results imply that the combination of miR‐21 gene silencing and Gem therapy using an scFv‐functionalized NP carrier exerted synergistic antitumor effects on pancreatic cancer cells, which is a promising strategy for pancreatic cancer therapy.