Preclinical evaluation of platinum-loaded hydroxyapatite nanoparticles in an embryonic zebrafish xenograft model

Nanoscale. 2020 Jul 2;12(25):13582-13594. doi: 10.1039/d0nr04064a.

Abstract

Hydroxyapatite (HA) nanoparticles are commonly used as building blocks in the design of bone-substituting biomaterials. Recently, these nanoparticles have been considered for the treatment of metastasis disease, since their pH-dependent dissolution behavior allows for precise tuning of release kinetics of loaded cargo. Herein we show that the capacity of drug-loaded nanoparticles stabilized with citrate ions reduce cancer cell survival in an embryonic zebrafish xenograft model. In particular, in vitro studies demonstrate that PtPP-loaded HA nanoparticles exhibit anti-proliferative activity against breast cancer cells at reduced pH. In vivo studies using an embryonic zebrafish xenograft model reveal that PtPP co-delivered with human breast cancer cells strongly reduce cancer cell survival. Similarly, co-injection of breast cancer cells with citrate-functionalized and PtPP-loaded HA nanoparticles into zebrafish significantly reduces survival of cancer cells due to release of chemotherapeutically active kiteplatin species. These results demonstrate the preclinical efficacy of drug-loaded nanoparticles against human breast cancer cells in a xenogenic embryonic in vivo model.

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Durapatite
  • Heterografts
  • Humans
  • Nanoparticles*
  • Platinum
  • Xenograft Model Antitumor Assays
  • Zebrafish

Substances

  • Platinum
  • Durapatite