Near infrared-responsive quinacrine-gold hybrid nanoparticles deregulate HSP-70/P300-mediated H3K14 acetylation in ER/PR+ breast cancer stem cells

Nanomedicine (Lond). 2024 Mar;19(7):581-596. doi: 10.2217/nnm-2023-0269. Epub 2024 Jan 31.

Abstract

Aim: This study aimed to determine if quinacrine-gold hybrid nanoparticles (QAuNPs) + near-infrared (NIR) deregulate HSP-70/P300 complex-mediated H3K14 acetylation in estrogen receptor/progesterone receptor (ER/PR+) breast cancer stem cells (CSCs). Materials & methods: Various cells and mouse-based systems were used as models. Results: QAuNP + NIR treatment reduced the nuclear translocation of HSP-70, affected the histone acetyltransferase activity of P300 and specifically decreased H3K14 acetylation in ER/PR+ breast CSCs. Finally, HSP-70 knockdown showed a reduction in P300 histone acetyltransferase activity, decreased H3K14 acetylation and inhibited activation of the TGF-β gene. Conclusion: This study revealed that QAuNP + NIR irradiation inhibits oncogenic activation of the TGF-β gene by decreasing H3K14 acetylation mediated through the HSP-70/P300 nuclear complex in ER/PR+ breast CSCs.

Keywords: HSP-70; MCF-7-CSCs; P300; T47D-CSCs; TGF-β; histone acetylation; near-infrared; quinacrine–gold hybrid nanoparticle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Female
  • Gold
  • Histone Acetyltransferases
  • Humans
  • Mice
  • Nanoparticles*
  • Neoplasms*
  • Neoplastic Stem Cells
  • Quinacrine / pharmacology
  • Transforming Growth Factor beta

Substances

  • Gold
  • Histone Acetyltransferases
  • Quinacrine
  • Transforming Growth Factor beta