Aptamers, Nucleotide; Drug Carriers; Phosphoinositide-3 Kinase Inhibitors; Polymers; Protein Kinase Inhibitors; EC 2.7.11.1 (TOR Serine-Threonine Kinases); Aptamers, Nucleotide/chemistry/metabolism; Blood-Brain Barrier/metabolism; Brain Neoplasms/drug therapy/metabolism; Cell Line, Tumor; Drug Carriers/chemistry/metabolism; Drug Delivery Systems; Glioblastoma/drug therapy/metabolism; Humans; Nanoparticles/chemistry/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Polymers/chemistry/metabolism; Protein Kinase Inhibitors/administration & dosage/pharmacokinetics; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
Résumé :
[en] 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 EC(50) 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.
Disciplines :
Oncologie
Auteur, co-auteur :
Monaco, Ilaria; Department of Industrial Chemistry "Toso Montanari", University of Bologna , Viale Risorgimento 4, 40136 Bologna, Italy.
Camorani, Simona; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore" (IEOS), Consiglio Nazionale delle Ricerche (CNR) , Via S. Pansini 5, 80131 Naples, Italy.
Colecchia, David; Istituto Toscano Tumori (ITT), Core Research Laboratory and Consiglio Nazionale delle Ricerche (CNR), Istituto di Fisiologia Clinica , Via Fiorentina 1, 53100, Siena, Italy.
Locatelli, Erica ; Department of Industrial Chemistry "Toso Montanari", University of Bologna , Viale Risorgimento 4, 40136 Bologna, Italy.
Calandro, Pierpaolo; Istituto Toscano Tumori (ITT), Core Research Laboratory and Consiglio Nazionale delle Ricerche (CNR), Istituto di Fisiologia Clinica , Via Fiorentina 1, 53100, Siena, Italy.
Oudin, Anais; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health , 84 Val Fleuri, Luxembourg L-1586, Luxembourg.
NICLOU, Simone P. ; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health , 84 Val Fleuri, Luxembourg L-1586, Luxembourg.
Arra, Claudio; Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS , via M. Semmola, 80131 Naples, Italy.
Chiariello, Mario; Istituto Toscano Tumori (ITT), Core Research Laboratory and Consiglio Nazionale delle Ricerche (CNR), Istituto di Fisiologia Clinica , Via Fiorentina 1, 53100, Siena, Italy.
Cerchia, Laura; Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore" (IEOS), Consiglio Nazionale delle Ricerche (CNR) , Via S. Pansini 5, 80131 Naples, Italy.
Comes Franchini, Mauro ; Department of Industrial Chemistry "Toso Montanari", University of Bologna , Viale Risorgimento 4, 40136 Bologna, Italy.
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Aptamer Functionalization of Nanosystems for Glioblastoma Targeting through the Blood-Brain Barrier.
Date de publication/diffusion :
25 mai 2017
Titre du périodique :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Maison d'édition :
American Chemical Society, Washington, Etats-Unis - District de Columbia
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