Exfoliated Black Phosphorus Promotes in Vitro Bone Regeneration and Suppresses Osteosarcoma Progression through Cancer-Related Inflammation Inhibition

ACS Appl Mater Interfaces. 2019 Mar 6;11(9):9333-9342. doi: 10.1021/acsami.8b21592. Epub 2019 Feb 22.

Abstract

Nowadays chemotherapy is the main treatment for osteosarcoma disease, even if limited by the lack of selectivity between healthy and cancer cells during the inhibition of cell division. Herein, we propose the use of few-layer two-dimensional black phosphorous (2D bP) as an alternative tool for osteosarcoma treatment and report how 2D bP can stimulate newly forming bone tissue generation after osteosarcoma resection. In our study, we have developed an in vitro model to evaluate the efficacy of 2D bP material with and without near-infrared light irradiation treatment, and we have demonstrated that the presence of 2D bP without treatment inhibits the metabolic activity of osteosarcoma cells (SAOS-2) while inducing both the proliferation and the osteogenic differentiation of human preosteoblast cells (HOb) and mesenchymal stem cells. Furthermore, we also propose an in vitro coculture model (SAOS-2 and HOb cell lines) in order to study the effect of 2D bP on inflammatory response related to cancer. On this coculture model, 2D bP may increase anti-inflammatory cytokine generation (i.e., interleukin-10) and inhibit proinflammatory mediators synthesis (i.e., interleukin-6), thus suggesting the opportunity to prevent cancer-related inflammation. Finally, we have demonstrated that 2D bP represents a promising candidate for future regenerative medicine and anticancer applications.

Keywords: biomaterials; bone cancer treatment; bone regeneration; bone-cancer-related inflammation; few-layer black phosphorus; tissue regeneration.

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Biocompatible Materials / therapeutic use
  • Bone Regeneration / drug effects*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Coculture Techniques
  • Disease Progression
  • Humans
  • Inflammation / prevention & control
  • Infrared Rays
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Phosphorus / chemistry*
  • Phosphorus / pharmacology
  • Phosphorus / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Biocompatible Materials
  • Interleukin-6
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Interleukin-10
  • Phosphorus