RPV-modified epirubicin and dioscin co-delivery liposomes suppress non-small cell lung cancer growth by limiting nutrition supply

Cancer Sci. 2020 Feb;111(2):621-636. doi: 10.1111/cas.14256. Epub 2020 Jan 18.

Abstract

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.

Keywords: angiogenesis; cell-penetrating peptide; co-delivery liposome; non-small cell lung cancer; vasculogenic mimicry.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell-Penetrating Peptides / chemistry*
  • Diosgenin / administration & dosage
  • Diosgenin / analogs & derivatives*
  • Diosgenin / chemistry
  • Diosgenin / pharmacology
  • Epirubicin / administration & dosage*
  • Epirubicin / chemistry
  • Epirubicin / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liposomes
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Neovascularization, Pathologic / drug therapy*
  • Rats
  • Xenograft Model Antitumor Assays

Substances

  • Cell-Penetrating Peptides
  • Liposomes
  • dioscin
  • Epirubicin
  • Diosgenin