Authors

Aman P Mann, Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX
Anoma Somasunderam, Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX
René Nieves-Alicea, Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX
Xin Li, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX
Austin Hu, Department of Biomedical Engineering, University of Texas Austin, Austin, TX
Anil K Sood, Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX
Mauro Ferrari, Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX; Department of Biomedical Engineering, University of Texas Austin, Austin, TX; Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 5 Department of Bioengineering, Rice University, Houston, TX; Department of Bioengineering, Rice University, Houston, TX
David G Gorenstein, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX
Takemi Tanaka, Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, Houston, TX; Department of Biomedical Engineering, University of Texas Austin, Austin, TX; Department of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, PAFollow

Document Type

Article

Publication Date

9-1-2010

Comments

This article has been peer reviewed and is published in PLoS One 2010, 5(9). The published version is available at DOI: 10.1371/journal.pone.0013050. © Public Library of Science

Abstract

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D) = 47 nM) while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition) of sLe(x) positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1) that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.

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