Aptamer Functionalization of Nanosystems for Glioblastoma Targeting through the Blood-Brain Barrier

J Med Chem. 2017 May 25;60(10):4510-4516. doi: 10.1021/acs.jmedchem.7b00527. Epub 2017 May 10.

Abstract

Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake into U87MG glioblastoma (GBM) cells and with astonishing EC50 value (38 pM) when loaded with a PI3K-mTOR inhibitor. We also demonstrated in vivo BBB passage and tumor accumulation in a GBM orthotopic model.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / metabolism
  • Blood-Brain Barrier / metabolism*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Delivery Systems
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Polymers / chemistry
  • Polymers / metabolism
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacokinetics
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Aptamers, Nucleotide
  • Drug Carriers
  • Phosphoinositide-3 Kinase Inhibitors
  • Polymers
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases