The Potential Selective Cytotoxicity of Poly (L- Lactic Acid)-Based Scaffolds Functionalized with Nanohydroxyapatite and Europium (III) Ions toward Osteosarcoma Cells.
Mateusz SikoraKlaudia MarcinkowskaKrzysztof MaryczRafał Jakub WigluszAgnieszka SmieszekPublished in: Materials (Basel, Switzerland) (2019)
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.
Keyphrases
- cell cycle arrest
- induced apoptosis
- quantum dots
- cell death
- poor prognosis
- adipose tissue
- endoplasmic reticulum stress
- tissue engineering
- signaling pathway
- obstructive sleep apnea
- lactic acid
- endothelial cells
- stem cells
- oxidative stress
- radiation therapy
- high resolution
- chronic kidney disease
- type diabetes
- end stage renal disease
- young adults
- insulin resistance
- risk assessment
- electron microscopy
- optical coherence tomography
- ejection fraction
- sensitive detection
- bone mineral density
- single molecule
- lymph node metastasis
- cell proliferation