Identification of thioaptamer ligand against E-selectin: Potential application for inflamed vasculature targeting

Aman P. Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K. Sood, Mauro Ferrari, David G. Gorenstein, Takemi Tanaka

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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 (KD = 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 sLex 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.

Original languageEnglish (US)
Article numbere13050
Pages (from-to)1-11
Number of pages11
JournalPLoS ONE
Issue number9
StatePublished - 2010

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Identification of thioaptamer ligand against E-selectin: Potential application for inflamed vasculature targeting'. Together they form a unique fingerprint.

Cite this