Grafting aptamers onto gold nanostars increases in vitro efficacy in a wide range of cancer cell types

Duncan Hieu M. Dam, Kayla S.B. Culver, Teri W. Odom

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We report the design of a nanoconstruct that can function as a cell-type independent agent by targeting the ubiquitous protein nucleolin. Gold nanostars (AuNS) loaded with high densities of nucleolin-specific DNA aptamer AS1411 (Apt-AuNS) produced anticancer effects in a panel of 12 cancer lines containing four representative subcategories. We found that the nanoconstructs could be internalized by cancer cells and trafficked to perinuclear regions. Apt-AuNS resulted in downregulation of antiapoptotic Bcl-2 mRNA expression by ca. 200% compared to cells without the nanoconstructs. The caspase 3/7 activity (apoptosis) and cell death in cancer cells treated with Apt-AuNS increased by 1.5 times and by ca. 17%, respectively, compared to cells treated with free AS1411 at over 10 times the concentration. Moreover, light-triggered release of aptamer from the AuNS further enhanced the in vitro efficacy of the nanoconstructs in the cancer line panel with a 2-fold increase in caspase activity and a 40% decrease in cell viability compared to treatment with Apt-AuNS only. In contrast, treatments of the nanoconstructs with or without light-triggered release on a panel of normal cell lines had no adverse effects.

Original languageEnglish
Pages (from-to)580-587
Number of pages8
JournalMolecular Pharmaceutics
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 3 2014

Keywords

  • anticancer agents
  • aptamers
  • gold nanostars
  • nucleolin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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