PAMAM-RGD Conjugates Enhance siRNA Delivery Through a Multicellular Spheroid Model of Malignant Glioma

被引：117

作者：

Waite, Carolyn L. ^{[1
]}

Roth, Charles M. ^{[1
,2
]}

机构：

[1] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA

[2] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA

来源：

BIOCONJUGATE CHEMISTRY | 2009年 / 20卷 / 10期

关键词：

TARGETED DRUG-DELIVERY; FUNCTIONALIZED DENDRIMERS; TUMOR SPHEROIDS; PHASE-I; CANCER; VECTORS; BINDING; CELL; OLIGONUCLEOTIDES; CILENGITIDE;

D O I：

10.1021/bc900228m

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Generation 5 poly(amidoamine) (PAMAM) dendrimers were modified by the addition of cyclic RGD targeting peptides and were evaluated for their ability to associate with siRNA and mediate siRNA delivery to U87 malignant glioma cells. PAMAM-RGD conjugates were able to complex with siRNA to form complexes of approximately 200 nm in size. Modest siRNA delivery was observed in U87 cell using either PAMAM or PAMAM-RGD conjugates. PAMAM-RGD conjugates prevented the adhesion of U87 cells to fibrinogen-coated plates, in a manner that depends on the number of RGD ligands per dendrimer. The delivery of siRNA through three-dimensional multicellular spheroids of U87 cells was enhanced using PAMAM-RGD conjugates compared to the native PAMAM dendrimers, presumably by interfering with integrin-ECM contacts present in a three-dimensional tumor model.

引用

页码：1908 / 1916

页数：9

共 38 条

[1] RNAi therapeutics: Principles, prospects and challenges [J].

Aagaard, Lars ;

Rossi, John J. .

ADVANCED DRUG DELIVERY REVIEWS, 2007, 59 (2-3) :75-86

[2] Synthesis, characterization, and biological evaluation of integrin αvβ3-targeted PAMAM dendrimers [J].

Boswell, C. Andrew ;

Eck, Peter K. ;

Regino, Celeste A. S. ;

Bernardo, Marcelino ;

Wong, Karen J. ;

Milenic, Diane E. ;

Choyke, Peter L. ;

Brechbiel, Martin W. .

MOLECULAR PHARMACEUTICS, 2008, 5 (04) :527-539

[3]

Cai Weibo, 2006, Anti-Cancer Agents in Medicinal Chemistry, V6, P407, DOI 10.2174/187152006778226530

[4] RGD conjugation to polyethyleneimine does not improve DNA delivery to bone marrow stromal cells [J].

Clements, Basak Acan ;

Bai, Jiang ;

Kucharski, Cezary ;

Farrell, Laura-Lee ;

Lavasanifar, Afsaneh ;

Ritchie, Bruce ;

Ghahary, Aziz ;

Uludag, Hasan .

BIOMACROMOLECULES, 2006, 7 (05) :1481-1488

[5] Spheroid preparation from hanging drops: characterization of a model of brain tumor invasion [J].

Del Duca, D ;

Werbowetski, T ;

Del Maestro, RF .

JOURNAL OF NEURO-ONCOLOGY, 2004, 67 (03) :295-303

[6] Cell adhesion molecules for targeted drug delivery [J].

Dunehoo, Alison L. ;

Anderson, Meagan ;

Majumdar, Sumit ;

Kobayashi, Naoki ;

Berkland, Cory ;

Siahaan, Teruna J. .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 95 (09) :1856-1872

[7] Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours [J].

Eskens, FALM ;

Dumez, H ;

Hoekstra, R ;

Perschl, A ;

Brindley, C ;

Böttcher, S ;

Wynendaele, W ;

Drevs, J ;

Verweij, J ;

van Oosterom, AT .

EUROPEAN JOURNAL OF CANCER, 2003, 39 (07) :917-926

[8] Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement [J].

Fischbach, Claudia ;

Kong, Hyun Joon ;

Hsiong, Susan X. ;

Evangelista, Marta B. ;

Yuen, Will ;

Mooney, David J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (02) :399-404

[9] Spheroid-based drug screen: considerations and practical approach [J].

Friedrich, Juergen ;

Seidel, Claudia ;

Ebner, Reinhard ;

Kunz-Schughart, Leoni A. .

NATURE PROTOCOLS, 2009, 4 (03) :309-324

[10] RNA interference in cancer [J].

Gartel, AL ;

Kandel, ES .

BIOMOLECULAR ENGINEERING, 2006, 23 (01) :17-34

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