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纳米羟基磷灰石和铕(III)离子功能化的聚(L-乳酸)基支架对骨肉瘤细胞的潜在选择性细胞毒性

The Potential Selective Cytotoxicity of Poly (L- Lactic Acid)-Based Scaffolds Functionalized with Nanohydroxyapatite and Europium (III) Ions toward Osteosarcoma Cells.

作者信息

Sikora Mateusz, Marcinkowska Klaudia, Marycz Krzysztof, Wiglusz Rafał Jakub, Śmieszek Agnieszka

机构信息

The Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw, 38 C Chelmonskiego St, 50-630 Wroclaw, Poland.

International Institute of Translational Medicine, Jesionowa 11 St, 55-124 Malin, Poland.

出版信息

Materials (Basel). 2019 Nov 18;12(22):3779. doi: 10.3390/ma12223779.

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 % Eu: 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.

摘要

骨肉瘤(OSA)是一种发生于儿童和成人的恶性骨肿瘤,预后较差。尽管化疗和手术技术有所进步,但骨肉瘤患者的生存率并未显著提高。目前,人们正在努力寻找新的选择性策略,以区分癌细胞和正常细胞。这包括开发具有抗癌特性的仿生支架,其能够同时支持和调节骨组织的正常再生。在本研究中,使用人骨肉瘤细胞:U-2 OS、Saos-2和MG-63测试了由纳米羟基磷灰石(nHAp)功能化并掺杂铕(III)离子-10 wt % 3 mol % Eu:nHAp@PLLA组成的支架的细胞毒性。人脂肪组织来源的基质细胞(HuASCs)作为未转化细胞用于确定载体的选择性细胞毒性。分析包括评估细胞形态(共聚焦/扫描电子显微镜(SEM))、代谢活性以及支架上培养物中的凋亡情况。所获结果表明,支架对所有OSA细胞系具有高细胞毒性,这与细胞活力下降、代谢活性恶化以及在mRNA和miRNA水平测定的凋亡因子激活有关。同时,生物材料不影响HuASCs的活力和增殖率。由于用发光铕离子进行了功能化,所获支架具有生物成像功能,因此可能在骨肉瘤的治疗诊断中得到应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e968/6888250/e58920bae3dd/materials-12-03779-g001.jpg

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