Cancer Targeted Gene Therapy for Inhibition of Melanoma Lung Metastasis with eIF3i shRNA Loaded Liposomes

Mol Pharm. 2020 Jan 6;17(1):229-238. doi: 10.1021/acs.molpharmaceut.9b00943. Epub 2019 Dec 10.

Abstract

Eukaryotic translation initiation factors 3i (eIF3i) is a proto-oncogene that is overexpressed in various tumors, reducing its expression by eIF3i shRNA is a promising strategy to inhibit tumor growth or metastasis. Tumor cell is the target of eIF3i shRNA so that tumor-site accumulation could be important for fulfilling its therapeutic effect. Thus, the iRGD modified liposome (R-LP) was rationally synthesized to enhance the antitumor effect by active targeted delivery of eIF3i shRNA to B16F10 melanoma cells. R-LP encapsulating eIF3i shRNA gene (R-LP/sheIF3i) were prepared by a film dispersion method. The transfection experiment proves that R-LP could effectively transfect B16F10 cells. R-LP/sheIF3i notably restrained the migration, invasion, and adhesion of melanoma cells in vitro. In a mouse model of lung metastasis, R-LP/sheIF3i administered by intravenous injection suppressed pulmonary metastasis of melanoma by dramatically downregulated eIF3i expression and subsequently inhibiting tumor neovascularization and tumor cells proliferation in vivo. Our results provide a basis for tumor cells targeting strategies to reduce the expression of eIF3i by RNAi in the treatment of tumor metastasis.

Keywords: B16F10 melanoma cells; eIF3i shRNA; iRGD; liposome; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Eukaryotic Initiation Factor-3 / genetics*
  • Eukaryotic Initiation Factor-3 / metabolism
  • Genetic Therapy*
  • Liposomes / chemistry
  • Liposomes / ultrastructure
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy
  • Male
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / secondary*
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Neovascularization, Pathologic / genetics
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use
  • RNA, Small Interfering
  • Transfection
  • Transplantation, Homologous

Substances

  • Eukaryotic Initiation Factor-3
  • Liposomes
  • N-end cysteine peptide tumor-homing peptide
  • Oligopeptides
  • RNA, Small Interfering