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

被引：109

作者：

Monaco, Ilaria ^{[1
]}

Camorani, Simona ^{[2
]}

Colecchia, David ^{[3
,4
]}

Locatelli, Erica ^{[1
]}

Calandro, Pierpaolo ^{[3
,4
]}

Oudin, Anais ^{[5
]}

Niclou, Simone ^{[5
]}

Arra, Claudio ^{[6
]}

Chiariello, Mario ^{[3
,4
]}

Cerchia, Laura ^{[2
]}

Franchini, Mauro Comes ^{[1
]}

机构：

[1] Univ Bologna, Dept Ind Chem Toso Montanari, Viale Risorgimento 4, I-40136 Bologna, Italy

[2] CNR, Ist Endocrinol & Oncol Sperimentale G Salvatore I, Via S Pansini 5, I-80131 Naples, Italy

[3] ITT, Core Res Lab, Via Fiorentina 1, I-53100 Siena, Italy

[4] CNR, Ist Fisiol Clin, Via Fiorentina 1, I-53100 Siena, Italy

[5] Luxembourg Inst Hlth, Dept Oncol, NorLux Neurooncol Lab, 84 Val Fleuri, L-1586 Luxembourg, Luxembourg

[6] IRCCS, Ist Nazl Studio & Cura Tumori Fdn G Pascale, Anim Facil Unit, Dept Expt Oncol, Via M Semmola, I-80131 Naples, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 60卷 / 10期

关键词：

DRUG-DELIVERY; CANCER; NANOPARTICLES; CELLS; GROWTH; GLIOMA; BETA; INHIBITION; THERAPY; SYSTEM;

D O I：

10.1021/acs.jmedchem.7b00527

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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,8 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.

引用

页码：4510 / 4516

页数：7

共 29 条

[1] Function of the Blood-Brain Barrier and Restriction of Drug Delivery to Invasive Glioma Cells: Findings in an Orthotopic Rat Xenograft Model of Glioma [J].

Agarwal, Sagar ;

Manchanda, Pooja ;

Vogelbaum, Michael A. ;

Ohlfest, John R. ;

Elmquist, William F. .

DRUG METABOLISM AND DISPOSITION, 2013, 41 (01) :33-39

[2] De-Repression of PDGFRβ Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients [J].

Akhavan, David ;

Pourzia, Alexandra L. ;

Nourian, Alex A. ;

Williams, Kevin J. ;

Nathanson, David ;

Babic, Ivan ;

Villa, Genaro R. ;

Tanaka, Kazuhiro ;

Nael, Ali ;

Yang, Huijun ;

Dang, Julie ;

Vinters, Harry V. ;

Yong, William H. ;

Flagg, Mitchell ;

Tamanoi, Fuyuhiko ;

Sasayama, Takashi ;

James, C. David ;

Kornblum, Harley I. ;

Cloughesy, Tim F. ;

Cavenee, Webster K. ;

Bensinger, Steven J. ;

Mischel, Paul S. .

CANCER DISCOVERY, 2013, 3 (05) :534-547

[3] Aptamer targeting EGFRvIII mutant hampers its constitutive autophosphorylation and affects migration, invasion and proliferation of glioblastoma cells [J].

Camorani, Simona ;

Crescenzi, Elvira ;

Colecchia, David ;

Carpentieri, Andrea ;

Amoresano, Angela ;

Fedele, Monica ;

Chiariello, Mario ;

Cerchia, Laura .

ONCOTARGET, 2015, 6 (35) :37579-37596

[4]

Camorani Simona, 2015, Central Nervous System Agents in Medicinal Chemistry, V15, P126

[5] Inhibition of Receptor Signaling and of Glioblastoma-derived Tumor Growth by a Novel PDGFRβ Aptamer [J].

Camorani, Simona ;

Esposito, Carla L. ;

Rienzo, Anna ;

Catuogno, Silvia ;

Iaboni, Margherita ;

Condorelli, Gerolama ;

de Franciscis, Vittorio ;

Cerchia, Laura .

MOLECULAR THERAPY, 2014, 22 (04) :828-841

[6] Tyrosine Kinase Inhibitor Gefitinib Enhances Topotecan Penetration of Gliomas [J].

Carcaboso, Angel M. ;

Elmeliegy, Mohamed A. ;

Shen, Jun ;

Juel, Stephen J. ;

Zhang, Ziwei M. ;

Calabrese, Christopher ;

Tracey, Lorraine ;

Waters, Christopher M. ;

Stewart, Clinton F. .

CANCER RESEARCH, 2010, 70 (11) :4499-4508

[7] The blood-brain barrier and cancer:: Transporters, treatment, and Trojan horses [J].

Deeken, John F. ;

Loescher, Wolfgang .

CLINICAL CANCER RESEARCH, 2007, 13 (06) :1663-1674

[8] Inhibition of DNA Double-Strand Break Repair by the Dual PI3K/mTOR Inhibitor NVP-BEZ235 as a Strategy for Radiosensitization of Glioblastoma [J].

del Alcazar, Carlos Rodrigo Gil ;

Hardebeck, Molly Catherine ;

Mukherjee, Bipasha ;

Tomimatsu, Nozomi ;

Gao, Xiaohuan ;

Yan, Jingsheng ;

Xie, Xian-Jin ;

Bachoo, Robert ;

Li, Li ;

Habib, Amyn A. ;

Burma, Sandeep .

CLINICAL CANCER RESEARCH, 2014, 20 (05) :1235-1248

[9] A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells [J].

Esposito, Carla L. ;

Nuzzo, Silvia ;

Kumar, Swati A. ;

Rienzo, Anna ;

Lawrence, Clare L. ;

Pallini, Roberto ;

Shaw, Lisa ;

Alder, Jane E. ;

Ricci-Vitiani, Lucia ;

Catuogno, Silvia ;

de Franciscis, Vittorio .

JOURNAL OF CONTROLLED RELEASE, 2016, 238 :43-57

[10] Whole-cell SELEX aptamer-functionalised poly(ethyleneglycol)-poly(ε-caprolactone) nanoparticles for enhanced targeted glioblastoma therapy [J].

Gao, Huile ;

Qian, Jun ;

Yang, Zhi ;

Pang, Zhiqing ;

Xi, Zhangjie ;

Cao, Shijie ;

Wang, Yuchen ;

Pan, Shuaiqi ;

Zhang, Shuang ;

Wang, Wei ;

Jiang, Xinguo ;

Zhang, Qizhi .

BIOMATERIALS, 2012, 33 (26) :6264-6272

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