基于活性Se/Ti-MOF的pH响应性水凝胶支架用于骨肉瘤 协同治疗与机制解析

ISSN:2705-098X(P)

EISSN:2705-0505(O)

语言:中文

作者
符光戌,王 勇,郭钟义,谭登武,张 珍
文章摘要
目的:针对骨肉瘤术后局部复发与骨缺损问题,构建一种新型硒/钛金属有机框架(Se/Ti-MOF)复合水凝胶支架,以实现从“载体”到“活性治疗剂”的转变,避免传统载药系统对化疗药物的依赖。方法:采用水热法合成Se/Ti-MOF纳米颗粒,并通过物理共混-交联技术将其固载于明胶/壳聚糖基质中,制备Se/Ti-MOF@Gel/CS复合支架。利用SEM、XRD、FT-IR表征结构;测试力学、溶胀及降解性能;采用ICP-MS分析离子释放动力学;通过CCK-8、流式细胞术与Western Blot评估体外抗肿瘤活性及机制。结果:成功制备Se/Ti-MOF纳米颗粒(112.5±16.3 nm)及贯通多孔复合支架(孔径25.6±8.7μm)。Se/Ti-MOF使支架压缩模量由18.4±2.1 kPa提升至36.8±3.5 kPa。在pH 5.5条件下,支架溶胀与降解增强,Se/Ti离子协同释放加快。支架浸提液对143B和HOS细胞具有选择性毒性(IC50分别为4.197和5.624μg/mL),其机制涉及G2/M期阻滞、ROS爆发及线粒体凋亡通路激活。结论:Se/Ti-MOF@Gel/CS复合支架兼具良好力学性能、pH响应性及选择性抗肿瘤活性,通过调控细胞周期与ROS-线粒体凋亡通路发挥作用,为骨肉瘤术后“抗肿瘤-骨修复”一体化治疗提供了新平台。
文章关键词
硒/钛金属有机框架;水凝胶支架;骨肉瘤;细胞凋亡;活性氧
参考文献
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