Turning On/Off the Anti-Tumor Effect of the Au Cluster via Atomically Controlling Its Molecular Size

Jiao Zhai, Yanwei Jia, Lina Zhao, Qing Yuan, Fuping Gao, Xiangchun Zhang, Pengju Cai, Liang Gao, Juanjuan Guo, Shuhong Yi, Zhifang Chai, Yuliang Zhao, Xueyun Gao

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We reported two Au clusters with precisely controlled molecular size (Au5Peptide3 and Au22Peptide10) showing different antitumor effects. In vitro, both Au5Peptide3 and Au22Peptide10 were well taken up by human nasopharyngeal cancer cells (CNE1 cells). However, only Au5Peptide3 significantly induced CNE1 cell apoptosis. Further studies showed that CNE1 cells took up Au5Peptide3 (1.98 × 10-15 mol/cell), and 9% of them entered mitochondria (0.186 × 10-15 mol/cell). As a comparison, the uptake of Au22Peptide10 was only half the amount of Au5Peptide3 (1.11 × 10-15 mol/cell), and only 1% of them entered mitochondria (0.016 × 10-15 mol/cell). That gave 11.6-fold more Au5Peptide3 in mitochondria of CNE1 cells than Au22Peptide10. Further cell studies revealed that the antitumor effect may be due to the enrichment of Au5Peptide3 in mitochondria. Au5Peptide3 slightly decreased the Mcl-1 (antiapoptotic protein of mitochondria) and significantly increased the Puma (pro-apoptotic protein of mitochondria) expression level in CNE1 cells, which resulted in mitochondrial transmembrane potential change and triggered the caspase 9-caspase 3-PARP pathway to induce CNE1 cell apoptosis. In vivo, CNE1 tumor growth was significantly suppressed by Au5Peptide3 in the xenograft model after 3 weeks of intraperitoneal injection. The TUNEL and immuno-histochemical studies of tumor tissue verified that CNE1 cell apoptosis was mainly via the Puma and Mcl-1 apoptosis pathway in the xenograft model, which matched the aforementioned CNE1 cell studies in vitro. The discovery of Au5 but not Au22 suppressing tumor growth via the mitochondria target was a breakthrough in the nanomedical field, as this provided a robust approach to turn on/off the nanoparticles' medical properties via atomically controlling their sizes.

Original languageEnglish (US)
Pages (from-to)4378-4386
Number of pages9
JournalACS Nano
Volume12
Issue number5
DOIs
StatePublished - May 22 2018

Keywords

  • Mcl-1
  • Puma
  • antitumor effect
  • cell apoptosis
  • mitochondria
  • peptide-Au cluster

ASJC Scopus subject areas

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

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