The promotion of salinomycin delivery to hepatocellular carcinoma cells through EGFR and CD133 aptamers conjugation by PLGA nanoparticles

Nanomedicine (Lond). 2015 Jul;10(12):1863-79. doi: 10.2217/nnm.15.43.

Abstract

Aims: To develop salinomycin-loaded poly(lactic-co-glycolic acid) nanoparticles conjugated with both CD133 aptamers A15 and EGFR aptamers CL4 (CESN), to target hepatocellular carcinoma (HCC) cells simultaneously expressing EGFR and CD133.

Materials & methods: The antitumor activity and mechanism of CESN were investigated.

Results & conclusion: The cytotoxicity of CESN in HCC cells and CD133(+) HCC cells was superior to that of A15 or CL4-conjugted or nontargeted salinomycin-loaded nanoparticles. The antitumor assay in mice bearing HCC xenograft tumors confirmed the superior antitumor activity of CESN over other controls. We speculated that the improved therapeutic effect of CESN may be attributed to both targeting a higher percentage of HCC cells and increased delivery of salinomycin to HCC cells.

Keywords: CD133; EGFR; hepatocellular carcinoma; nanoparticles; salinomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Antigens, CD / genetics*
  • Antineoplastic Agents / administration & dosage
  • Aptamers, Nucleotide / genetics
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Synergism
  • ErbB Receptors / genetics*
  • Glycoproteins / genetics*
  • Humans
  • Lactic Acid / chemistry
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Molecular Targeted Therapy / methods
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Nanoconjugates / administration & dosage
  • Nanoconjugates / chemistry
  • Nanoconjugates / ultrastructure
  • Particle Size
  • Peptides / genetics*
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pyrans / administration & dosage*
  • Pyrans / chemistry
  • Treatment Outcome

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Glycoproteins
  • Nanocapsules
  • Nanoconjugates
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Pyrans
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • salinomycin
  • EGFR protein, human
  • ErbB Receptors