Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation

Biomaterials. 2017 Mar:121:1-14. doi: 10.1016/j.biomaterials.2016.12.031. Epub 2016 Dec 28.

Abstract

Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.

Keywords: Bioactivity; Calcium phosphate; Drug delivery; Osteogenic differentiation; Osteosarcoma.

MeSH terms

  • Absorbable Implants
  • Adenosine / administration & dosage*
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Antineoplastic Agents / administration & dosage
  • Calcium Phosphates / administration & dosage*
  • Capsules / administration & dosage
  • Capsules / chemical synthesis*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Female
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred BALB C
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / physiology
  • Osteogenesis / drug effects
  • Osteogenesis / physiology
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Phosphorylation
  • Porosity
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Calcium Phosphates
  • Capsules
  • Doxorubicin
  • calcium phosphate
  • Adenosine