Abstract
Osteosarcoma (OSA) is malignant bone tumor, occurring in children and adults, characterized by poor prognosis. Despite advances in chemotherapy and surgical techniques, the survival of osteosarcoma patients is not improving significantly. Currently, great efforts are taken to identify novel selective strategies, distinguishing between cancer and normal cells. This includes development of biomimetic scaffolds with anticancer properties that can simultaneously support and modulate proper regeneration of bone tissue. In this study cytotoxicity of scaffolds composed from poly (L-lactic acid) functionalized with nanohydroxyapatite (nHAp) and doped with europium (III) ions—10 wt % 3 mol % Eu3+: nHAp@PLLA was tested using human osteosarcoma cells: U-2 OS, Saos-2 and MG-63. Human adipose tissue-derived stromal cells (HuASCs) were used as non-transformed cells to determine the selective cytotoxicity of the carrier. Analysis included evaluation of cells morphology (confocal/scanning electron microscopy (SEM)), metabolic activity and apoptosis profile in cultures on the scaffolds. Results obtained indicated on high cytotoxicity of scaffolds toward all OSA cell lines, associated with a decrease of cells’ viability, deterioration of metabolic activity and activation of apoptotic factors determined at mRNA and miRNA levels. Simultaneously, the biomaterials did not affect HuASCs’ viability and proliferation rate. Obtained scaffolds showed a bioimaging function, due to functionalization with luminescent europium ions, and thus may find application in theranostics treatment of OSA.
Highlights
Osteosarcoma (OSA) is well-examined neoplasm, which belongs to the group of bone-tissue sarcomas producing osteoid
Observations performed using confocal microscope revealed that osteosarcoma cell lines cultured in the presence of biomaterial had poorly developed cytoskeleton and did not form an integral monolayer, which was characteristic for cultures on polystyrene surface
The number of progenitor cells (HuASC) was reduced in cultures propagated on the biomaterial, unlike for osteosarcoma cells, no significant changes were noticed in terms of actin organization
Summary
Osteosarcoma (OSA) is well-examined neoplasm, which belongs to the group of bone-tissue sarcomas producing osteoid. No survival advantage to amputation over limb-salvage procedures was found in a large retrospective studies presented by Simon et al (1986) and Gherlinzoni et al (1992) [10,11] Given this fact, the limb salvage surgery is more frequently suggested, especially when proper surgical margins can be achieved [12,13,14]. Primary chemotherapeutics used for the treatment of osteosarcoma are: adriamycin (ADM), cisplatin (DDP), high-dose methotrexate (HD-MTX), ifosfamide (IFO) and epirubicin (EPI) [15]. These drugs improve the survival rate of patients with osteosarcoma, their efficacy is usually associated with the application of high-intensity doses
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