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Title
  • en Construction of an Aptamer Modified Liposomal System Targeted to Tumor Endothelial Cells
Creator
Accessrights open access
Subject
  • Other en aptamer based liposome
  • Other en targeted drug delivery
  • Other en tumor endothelial cell
  • Other en heat shock protein 70 (HSP70)
  • Other en cell-based systematic evolution of ligands by exponential enrichment
  • NDC 499
Description
  • Abstract en We describe herein the development of a high affinity and specific DNA aptamer as a new ligand for use in liposomal nanoparticles to target cultured mouse tumor endothelial cells (mTECs). Active targeted nanotechnology based drug delivery systems are currently of great interest, due to their potential for reducing side effects and facilitating the delivery of cytotoxic drugs or genes in a site specific manner. In this study, we report on a promising aptamer candidate AraHH036 that shows selective binding towards mTECs. The aptamer does not bind to normal cells, normal endothelial cells or tumor cells. Therefore, we synthesized an aptamer-polyethylene glycol (PEG) lipid conjugate and prepared aptamer based liposomes (ALPs) by the standard lipid hydration method. First, we quantified the higher capacity of ALPs to internalize into mTECs by incubating ALPs containing 1 mol%, 5 mol% and 10 mol% aptamer of total lipids and compared the results to those for unmodified PEGylated liposomes (PLPs). A confocal laser scanning microscope (CLSM) uptake study indicated that the ALPs were taken up more efficiently than PLPs. The measured K-d value of the ALPs was 142 nM. An intracellular trafficking study confirmed that most of the rhodamine labeled ALPs were taken up and co-localized with the green lysotracker, thus confirming that they were located in lysosomes. Finally, using an aptamer based proteomics approach, the molecular target protein of the aptamer was identified as heat shock protein 70 (HSP70). The results suggest that these ALPs offer promise as a new carrier molecule for delivering anti-angiogenesis drugs to tumor vasculature.
Publisher en The Pharmaceutical Society of Japan
Date
    Issued2014-11
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/57651
Relation
  • isIdenticalTo DOI https://doi.org/10.1248/bpb.b14-00338
  • PMID 25366480
Journal
    • PISSN 0918-6158
      • en Biological & pharmaceutical bulletin
      • Volume Number37 Issue Number11 Page Start1742 Page End1749
File
Oaidate 2023-07-26