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