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Catechins-Modified Selenium-Doped Hydroxyapatite Nanomaterials for Improved Osteosarcoma Therapy Through Generation of Reactive Oxygen Species
日期: 2020-04-09
浏览次数:

出版物名称:Frontiers in Oncology

ISSN:2234-943X

第一作者:
通讯作者:杨光、万杰
文章类型:Article
IF:4.28
中科院分区:1

合作单位:1.郑州大学;2. 中国科学院水生生物研究所;3.北京中国科学院大学;4.河南省转化型脑血管病医学重点实验室;5.华中科技大学材料科学与工程学院

Abstract
Osteosarcoma is the most common bone cancer with limited therapeutic options. It can be treated by selenium-doped hydroxyapatite owing to its known antitumor potential. However, a high concentration of Se is toxic toward normal and stem cells whereas its low concentration cannot effectively remove cancer cells. Therefore, the current study was aimed to improve the anticancer activity of Se-HAp nanoparticles through catechins (CC) modification owing to their high cancer therapeutic value. The sequentially developed catechins modified Se-HAp nanocomposites (CC/Se-HAp) were characterized for various physico-chemical properties and antitumor activity. Structural analysis showed the synthesis of small rod-like single phase HAp nanoparticles (60 ± 15 nm), which effectively interacted with Se and catechins and formed agglomerated structures. TEM analysis showed the internalization and degradation of CC/Se-HAp nanomaterials within MNNG/HOS cells through a non-specific endocytosis process. Cell toxicity analysis showed that catechins modification improved the antitumor activity of Se-HAp nanocomposites by inducing apoptosis of human osteosarcoma MNNG/HOS cell lines, through generation of reactive oxygen species (ROS) which in turn activated the caspase-3 pathway, without significantly affecting the growth of human normal bone marrow stem cells (hBMSCs). qPCR and western blot analyses revealed that casp3, p53, and bax genes were significantly upregulated while cox-2 and PTK-2 were slightly downregulated as compared to control in CC/Se-HAp-treated MNNG/HOS cell lines. The current study of combining natural biomaterial (i.e., catechins) with Se and HAp, can prove to be an effective therapeutic approach for bone cancer therapy.


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