Apoptosis induced inn osteosarcome cells by drug delivery biomaterials

Osteosarcoma (OS) is a bone cancer, which affects pediatric/young adult and elderly patients. In recent years, novel drug‐delivery system approaches with bioactive bone substitutes have been proposed with the objectives to induce OS cell death and bone regrowth. Herein, injectable nanostructured strontium-doped calcium phosphate scaffold (SrCPC) was investigated as drug delivery system to combine bone regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The osteoinductivity of SrCPC was investigated analysing osteogenic activities in an in vitro model of human adipose stem cells (hASCs), such as (i) mineral matrix deposition by Alizarin Red Staining, (ii) osteocalcin protein expression by E.L.I.S.A. (III) osteogenic gene expression by Real-Time PCR Array. Drug-loaded biomaterials were tested in an in vitro model of human OS cell lines, named SAOS‐2, U2-OS, and genetically engineered SAOS‐2‐eGFP. The ability of scaffolds to induce OS cell death was assessed investigating cell proliferation, by Caspase‐3/7 activities, and Annexin V/IP positivity. To determine if OS cells grown on doped‐scaffolds change their migratory ability, wound‐healing assay was performed. SrCPC demonstrates a good cytocompatibility and upregulation of osteogenic genes, together with OCN protein expression and mineral matrix deposition. SrCPC-MTX and SrCPC-DOX induced cell‐killing effects and apoptosis in OS cell lines up to day 7. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements seems to be a promising approach aiming to combine anticancer therapy and bone regrowth