Oncotarget

Research Papers:

Thioaptamer Conjugated Liposomes for Tumor Vasculature Targeting

Aman P. Mann, Rohan C. Bhavane, Anoma Somasunderam, Brenda Liz Montalvo-Ortiz, Ketan B. Ghaghada, David Volk, René Nieves-Alicea, K. Stephen Suh, Mauro Ferrari, Ananth Annapragada, David G. Gorenstein and Takemi Tanaka _

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Oncotarget. 2011; 2:298-304. https://doi.org/10.18632/oncotarget.261

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Abstract

Aman P. Mann1,6, Rohan C. Bhavane2, Anoma Somasunderam3, Brenda Liz Montalvo-Ortiz4 , Ketan B. Ghaghada2, David Volk3, René Nieves-Alicea5, K. Stephen Suh5, Mauro Ferrari6, Ananth Annapragada2, David G. Gorenstein3, Takemi Tanaka4

1 Department of Nanomedicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, Texas, 77030

2 School of Biomedical Informatics, University of Texas Health Science Center at Houston, 7000 Fannin, Houston, Texas, 77030

3 Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, Texas, 77030

4 Department of Pharmaceutical Sciences, Thomas Jefferson University,130 South 9th Street, Philadelphia, PA, 19107

5 The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, 07601

6 The Methodist Hospital Research Institute, Houston, Texas, 77030

Keywords: drug delivery; aptamer; E-selectin

Received: April 11, 2011; Accepted: May 6, 2011; Published: May 7, 2011;

Correspondence:

Takemi Tanaka, e-mail:

Abstract

Recent developments in multi-functional nanoparticles offer a great potential for targeted delivery of therapeutic compounds and imaging contrast agents to specific cell types, in turn, enhancing therapeutic effect and minimizing side effects. Despite the promise, site specific delivery carriers have not been translated into clinical reality. In this study, we have developed long circulating liposomes with the outer surface decorated with thioated oligonucleotide aptamer (thioaptamer) against E-selectin (ESTA) and evaluated the targeting efficacy and PK parameters. In vitro targeting studies using Human Umbilical Cord Vein Endothelial Cell (HUVEC) demonstrated efficient and rapid uptake of the ESTA conjugated liposomes (ESTA-lip).  In vivo, the intravenous administration of ESTA-lip resulted in their accumulation at the tumor vasculature of breast tumor xenografts without shortening the circulation half-life. The study presented here represents an exemplary use of thioaptamer for targeting and opens the door to testing various combinations of thioaptamer and nanocarriers that can be constructed to target multiple cancer types and tumor components for delivery of both therapeutics and imaging agents.


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