Enhanced Human Epidermal Growth Factor Receptor 2 Degradation in Breast Cancer Cells by Lysosome-Targeting Gold Nanoconstructs

Hyojin Lee, Duncan Hieu M Dam, Ji Won Ha, Jun Yue, Teri W Odom

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

This paper describes how gold nanoparticle nanoconstructs can enhance anticancer effects of lysosomal targeting aptamers in breast cancer cells. Nanoconstructs consisting of anti-HER2 aptamer (human epidermal growth factor receptor 2, HApt) densely grafted on gold nanostars (AuNS) first targeted HER2 and then were internalized via HER2-mediated endocytosis. As incubation time increased, the nanoconstruct complexes were found in vesicular structures, starting from early endosomes to lysosomes as visualized by confocal fluorescence and differential interference contrast microscopy. Within the target organelle, lysosomes, HER2 was degraded by enzymes at low pH, which resulted in apoptosis. At specific time points related to the doubling time of the cancer cells, we found that accumulation of HER2-HApt-AuNS complexes in lysosomes, lysosomal activity, and lysosomal degradation of HER2 were positively correlated. Increased HER2 degradation by HApt-AuNS triggered cell death and cell cycle arrest in the G0/G1 phase inhibition of cell proliferation. This work shows how a perceived disadvantage of nanoparticle-based therapeutics - the inability of nanoconstructs to escape from vesicles and thus induce a biological response - can be overcome by both targeting lysosomes and exploiting lysosomal degradation of the biomarkers.

Original languageEnglish
Pages (from-to)9859-9867
Number of pages9
JournalACS Nano
Volume9
Issue number10
DOIs
Publication statusPublished - Sep 3 2015

Fingerprint

lysosomes
breast
Gold
cancer
Cells
Cell death
gold
degradation
Degradation
Nanoparticles
Cell proliferation
Biomarkers
Microscopic examination
Enzymes
Fluorescence
nanoparticles
organelles
Apoptosis
biomarkers
apoptosis

Keywords

  • DNA aptamers
  • gold nanostars
  • lysosomes
  • nanoparticles
  • targeted drug delivery

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Enhanced Human Epidermal Growth Factor Receptor 2 Degradation in Breast Cancer Cells by Lysosome-Targeting Gold Nanoconstructs. / Lee, Hyojin; Dam, Duncan Hieu M; Ha, Ji Won; Yue, Jun; Odom, Teri W.

In: ACS Nano, Vol. 9, No. 10, 03.09.2015, p. 9859-9867.

Research output: Contribution to journalArticle

Lee, Hyojin ; Dam, Duncan Hieu M ; Ha, Ji Won ; Yue, Jun ; Odom, Teri W. / Enhanced Human Epidermal Growth Factor Receptor 2 Degradation in Breast Cancer Cells by Lysosome-Targeting Gold Nanoconstructs. In: ACS Nano. 2015 ; Vol. 9, No. 10. pp. 9859-9867.
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