Functionalized selenium nanoparticles for targeted delivery of doxorubicin to improve non-small-cell lung cancer therapy

Int J Nanomedicine. 2018 Oct 30:13:6929-6939. doi: 10.2147/IJN.S174909. eCollection 2018.

Abstract

Background: Selenium nanoparticles (SeNPs) loaded with chemotherapeutic drugs provided a novel perspective for cancer therapy.

Materials and methods: Here, SeNPs were modified with cyclic peptide (Arg-Gly-Asp-d-Phe-Cys [RGDfC]) to fabricate tumor-targeting delivery carrier RGDfC-SeNPs and, then, doxorubicin (DOX) was loaded to the surface of RGDfC-SeNPs for improving the antitumor efficacy of DOX in non-small-cell lung carcinoma therapy.

Results: The chemical structure characterization of RGDfC-Se@DOX showed that DOX was successfully loaded to the surface of RGDfC-SeNPs to prepare functionalized antitumor drug delivery system RGDfC-Se@DOX. RGDfC-Se@DOX exhibited effective cellular uptake in A549 cells and entered A549 cells mainly by clathrin-mediated endocytosis pathway. Compared to free DOX or Se@DOX at the equivalent dose of DOX, RGDfC-Se@DOX showed greater activity to inhibit A549 cells' proliferation and migration/invasion and induce A549 cells' apoptosis. More importantly, compared with passive targeting delivery system Se@DOX, active targeting delivery system RGDfC-Se@DOX exhibited more significant antitumor efficacy in vivo.

Conclusion: Taken together, RGDfC-Se@DOX may be a novel promising drug candidate for the lung carcinoma therapy.

Keywords: RGDfC peptide; antitumor; apoptosis; chemotherapy; nanoscale drug carrier.

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Drug Delivery Systems*
  • Drug Liberation
  • Endocytosis / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasm Invasiveness
  • Selenium / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Doxorubicin
  • Selenium