Gefitinib-loaded DSPE-PEG2000 nanomicelles with CD133 aptamers target lung cancer stem cells

World J Surg Oncol. 2017 Aug 30;15(1):167. doi: 10.1186/s12957-017-1230-4.

Abstract

Background: Lung cancer stem cells (CSCs) are considered to be the seed of lung cancer, and CD133 is a marker of lung CSCs. Here, we developed gefitinib-loaded poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles with CD133 aptamers (M-Gef-CD133) to eliminate CD133+ lung CSCs.

Methods: M-Gef-CD133 was prepared using a lipid-film-based approach. The targeting and activity of M-Gef-CD133 towards lung CSCs were evaluated.

Results: M-Gef-CD133 were small (25 nm) and showed enhanced cytotoxic effect towards CD133+ lung CSCs compared with non-targeted M-Gef and gefitinib. Notably, M-Gef-CD133 could significantly reduce tumor sphere formation and the percentage of CD133+ lung CSCs, indicating that it possesses selective toxicity against CD133+ lung CSCs.

Conclusions: The interaction of CD133 aptamers and CD133 shows promise in the delivery of gefitinib to CD133+ lung CSCs, and M-Gef-CD133 represents a promising treatment to target lung CSCs.

Keywords: CD133; Cancer stem cells; Gefitinib; Lung cancer; Nanomicelles.

MeSH terms

  • A549 Cells
  • AC133 Antigen / antagonists & inhibitors*
  • AC133 Antigen / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Aptamers, Peptide / chemistry
  • Drug Carriers / chemistry*
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mice
  • Mice, SCID
  • Nanoparticles / chemistry
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Quinazolines / pharmacology*
  • Quinazolines / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • AC133 Antigen
  • Antineoplastic Agents
  • Aptamers, Peptide
  • Drug Carriers
  • PROM1 protein, human
  • Phosphatidylethanolamines
  • Quinazolines
  • Polyethylene Glycols
  • Gefitinib