Monaco Ilaria, Camorani Simona, Colecchia David, Locatelli Erica, Calandro Pierpaolo, Oudin Anais, Niclou Simone, Arra Claudio, Chiariello Mario, Cerchia Laura, Comes Franchini Mauro
Department of Industrial Chemistry "Toso Montanari", University of Bologna , Viale Risorgimento 4, 40136 Bologna, Italy.
Istituto per l'Endocrinologia e l'Oncologia Sperimentale "G. Salvatore" (IEOS), Consiglio Nazionale delle Ricerche (CNR) , Via S. Pansini 5, 80131 Naples, Italy.
J Med Chem. 2017 May 25;60(10):4510-4516. doi: 10.1021/acs.jmedchem.7b00527. Epub 2017 May 10.
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 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.
当与特定靶向剂偶联时，聚合物纳米颗粒（PNP）可有效地将体内治疗剂递送至肿瘤。Gint4.T适配体可特异性识别血小板衍生生长因子受体β，并可穿过血脑屏障（BBB）。我们合成了与Gint4.T偶联的PNP，其能够被U87MG胶质母细胞瘤（GBM）细胞高效摄取，并且在装载PI3K-mTOR抑制剂时具有惊人的EC值（38 pM）。我们还在GBM原位模型中证明了其在体内穿过血脑屏障及肿瘤蓄积的情况。
