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, Takemi Tanaka

Research output: Contribution to journalArticle

71 Scopus citations

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 (ESTAlip). 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.

Original languageEnglish (US)
Pages (from-to)298-304
Number of pages7
JournalOncotarget
Volume2
Issue number4
DOIs
StatePublished - 2011

Keywords

  • Cancer
  • Liposomes
  • Nanoparticles
  • Therapy
  • Tumor vasculature

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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