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

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• 作者：Hyojin Lee ; Duncan Hieu M. Dam ; Ji Won Ha ; Jun Yue ; Teri W. Odom
• 刊名：ACS Nano
• 出版年：2015
• 出版时间：October 27, 2015
• 年：2015
• 卷：9
• 期：10
• 页码：9859-9867
• 全文大小：546K
• ISSN：1936-086X

文摘

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鈥攖he inability of nanoconstructs to escape from vesicles and thus induce a biological response鈥攃an be overcome by both targeting lysosomes and exploiting lysosomal degradation of the biomarkers.