Selenium-doped calcium phosphate biomineral reverses multidrug resistance to enhance bone tumor chemotherapy

Nanomedicine. 2021 Feb:32:102322. doi: 10.1016/j.nano.2020.102322. Epub 2020 Nov 10.

Abstract

The construction of a functional drug delivery system to reverse the multidrug resistance (MDR) of bone tumors in cases of failed chemotherapy remains a challenge. Herein, we demonstrate a selenium-doped calcium phosphate (Se-CaP) biomineral with high biocompatibility, biodegradability and pH-sensitive drug release properties. Se-CaP may not only serve as an effective drug-carrier to enhance the uptake of doxorubicin (DOX), but may also synchronously induce caspases-mediated apoptosis of osteosarcoma by generating intracellular reactive oxygen species (ROS). Furthermore, in vitro and in vivo studies obviously demonstrate that Se-CaP can reverse the MDR of osteosarcoma by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, DOX-loaded Se-CaP can significantly inhibit DOX-resistant MG63 (MG63/DXR) tumor growth in nude mice. Considering its biomimetic chemical properties, the Se-CaP biomineral, with the multiple functions mentioned above, could be a promising candidate for treating bone tumors with MDR characteristics.

Keywords: Biomineral; Calcium phosphate; Drug delivery; Multidrug resistance; Osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Calcium Phosphates / chemistry*
  • Cell Death
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans
  • Microspheres
  • Minerals / chemistry*
  • Reactive Oxygen Species / metabolism
  • Selenium / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Calcium Phosphates
  • Minerals
  • Reactive Oxygen Species
  • Doxorubicin
  • Selenium