Toward a doxorubicin-loaded bioinspired bone cement for the localized treatment of osteosarcoma

Future Oncol. 2021 Sep;17(26):3511-3528. doi: 10.2217/fon-2021-0128. Epub 2021 Jul 2.

Abstract

Aims: Osteosarcoma represents the second most common cause of death in children and young adults. No biomaterial allowing local drug delivery has been specifically developed. However, a biocompatible bioactive implantable material could prevent some amputations, and the local release of an antitumor agent could limit risks of relapse and metastasis. Methods: We propose a proof of concept of a self-setting paste combining amorphous calcium phosphate and doxorubicin-loaded particles of bone-like carbonated nanocrystalline apatite, as a means of local release. Results: The cement formulation and doping, first with folic acid and then with doxorubicin, was successful. Its physicochemistry was scrutinized. Preliminary in vivo data on an invasive osteosarcoma rat model suggest a limiting effect on metastatic events in the lungs without signs of toxicity.

Keywords: ACP bone cement; bioinspired particles; doxorubicin; in vivo invasive model; metastasis limitation; nanocrystalline apatite; osteosarcoma local treatment.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis
  • Biocompatible Materials
  • Bone Cements / chemistry*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Calcium Phosphates / chemistry*
  • Cell Proliferation
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Rats
  • Rats, Nude
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Biocompatible Materials
  • Bone Cements
  • Calcium Phosphates
  • amorphous calcium phosphate
  • Doxorubicin