Platinum-loaded, selenium-doped hydroxyapatite nanoparticles selectively reduce proliferation of prostate and breast cancer cells co-cultured in the presence of stem cells

J Mater Chem B. 2020 Apr 8;8(14):2792-2804. doi: 10.1039/d0tb00390e.

Abstract

Chemotherapeutic treatment of patients with bone tumors or bone metastases often leads to severe side effects such as high drug toxicity, lack of tumor specificity and induced drug resistance. A novel strategy to treat early stages of bone metastases involves local co-delivery of multiple chemotherapeutic agents to synergistically improve the curative effect and overcome shortcomings of traditional chemotherapy. Herein we show that selenite-doped hydroxyapatite nanoparticles loaded with a hydroxyapatite-binding anti-tumor platinum complex (PtPP-HASe) selectively reduce proliferation of cancer cells without reducing proliferation of bone marrow stem cells. These PtPP-HASe particles were nanocrystalline with selenium (Se) and platinum (Pt) contents ranging between 0-10 and 1.5-3 wt%, respectively. Release kinetics of Se and Pt from PtPP-HASe nanoparticles resulted in a cumulative release of ∼10 and ∼66 wt% after 7 days, respectively. At a Pt/Se ratio of 8, released Pt and Se species selectively reduced cell number of human prostate (PC3) and human breast cancer cells (MDA-MB-231) by a factor of >10 with limited effects on co-cultured human bone marrow stem cells (hBMSc). These novel nanoparticles demonstrate high anti-cancer selectivity, which offers ample opportunities for the design of novel biomaterials with potent and selective chemotherapeutic efficacy against cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques*
  • Drug Liberation
  • Drug Screening Assays, Antitumor
  • Durapatite / chemistry
  • Durapatite / pharmacology
  • Humans
  • Kinetics
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Platinum / chemistry
  • Platinum / pharmacology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Selenium / chemistry
  • Selenium / pharmacology
  • Stem Cells / drug effects*
  • Surface Properties
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Platinum
  • Durapatite
  • Selenium