负载丹参酮ⅡA的磁性纳米粒子Fe_(3)O_(4)@ZIF-8 MOF制备、对骨髓间充质干细胞增殖和成骨分化促进作用观察  

Preparation of magnetic nanoparticle Fe_(3)O_(4)@ZIF-8 MOF loaded with tanshinoneⅡA and its effects on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

作　　者：蒙泽婧 龙海军 陈滕 汪祖华 朱月 MENG Zejing;LONG Haijun;CHEN Teng;WANG Zuhua;ZHU Yue(College of Pharmaceutical Sciences,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;不详)

机构地区：[1]贵州中医药大学药学院,贵阳550025 [2]贵州中医药大学纳米药物研究中心

出　　处：《山东医药》2024年第24期24-28,共5页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(32160227);贵州省科技厅基础研究计划项目(黔科合基础-ZK[2022]一般513);贵州省教育厅青年科技人才成长项目(黔教合KY字[2022]252号)。

摘　　要：目的制备负载丹参酮ⅡA的磁性纳米粒子Fe_(3)O_(4)@ZIF-8MOF(Fe_(3)O_(4)@ZIF-8@TanⅡA),并观察Fe_(3)O_(4)@ZIF-8@TanⅡA对骨髓间充质干细胞(BMSCs)增殖、成骨分化的促进作用。方法 用沸石咪唑酯骨架材料(ZIF-8)对Fe_(3)O_(4)纳米粒进行表面修饰,将丹参酮ⅡA(TanⅡA)装载载入磁性纳米粒子Fe_(3)O_(4)@ZIF-8 MOF中,HPLC检测Fe_(3)O_(4)@ZIF-8@TanⅡA的载药量和包封率,测算Fe_(3)O_(4)@ZIF-8@TanⅡA的药物释放率。BMSCs细胞经体外培养后分为4组,对照组加入成骨诱导液+完全培养基,游离药物组加入成骨诱导液+含10.27μg/m L的TanⅡA完全培养基,载体组加入成骨诱导液+含100μg/m L的Fe_(3)O_(4)@ZIF-8 MOF完全培养基,载药组加入成骨诱导液+含100μg/m L的Fe_(3)O_(4)@ZIF-8@TanⅡA完全培养基,采用MTT法检测各组不同时点(给药1、4、7 d)细胞OD值,碱性磷酸酶(ALP)试剂盒检测不同时点(给药1、4 d)ALP活性。结果 Fe_(3)O_(4)@ZIF-8@TanⅡA的平均粒径为307.12 nm,PDI为0.090,电位为-40.03 m V,呈类球形,表面较为粗糙,比表面积为337.32 m^(2)/g,磁饱和强度约为48 emu/g,具有良好的超顺磁性;Fe_(3)O_(4)@ZIF-8@TanⅡA的载药量为10.27%,包封率为80.36%,体外释放具有p H响应性,能在骨质疏松微环境中加快释药速率。与对照组比较,载药组给药4 d细胞OD值增加,其余3组给药7 d细胞OD值增加(P均<0.05);与对照组比较,载药组给药1 d细胞ALP活性增强,载体组和载药组给药4 d细胞ALP活性增强(P均<0.05)。结论 Fe_(3)O_(4)@ZIF-8@TanⅡA具有良好的载药性能和超顺磁性,有较高的载药量和包封率,并能达到缓慢释放药物的效果,且能够改善TanⅡA水溶性、成药性差等缺点,Fe_(3)O_(4)@ZIF-8@TanⅡA对BMSCs的增殖和分化具有协同促进作用。Objective To prepare the magnetic nanoparticle Fe_(3)O_(4)@ZIF-8 MOF(Fe_(3)O_(4)@ZIF-8@TanⅡA)loaded with tanshinoneⅡA,and to observe the promoting effects of Fe_(3)O_(4)@ZIF-8@TanⅡA on proliferation and osteogenic differ-entiation of bone marrow mesenchymal stem cells(BMSCs).Methods Fe_(3)O_(4) nanoparticles were surface-modified with zeolite imidazolate skeleton material(ZIF-8),and tanshinoneⅡA(TanⅡA)was loaded into magnetic nanoparticle Fe_(3)O_(4)@ZIF-8 MOF and the drug loading and encapsulation rate of Fe_(3)O_(4)@ZIF-8@TanⅡA were detected by HPLC,and the drug release rate of Fe_(3)O_(4)@ZIF-8@TanⅡA was calculated.BMSCs were divided into four groups after culture in vitro.BMSCs in the control group were added with osteogenic induction solution+complete medium;BMSCs in the free drug group were added with osteogenic induction solution+TanⅡA complete medium containing 10.27µg/mL;BMSCs in the carrier group were added with osteogenic induction solution+Fe_(3)O_(4)@ZIF-8 MOF complete medium containing 100µg/mL;in the drug loading group,osteogenic induction solution+Fe_(3)O_(4)@ZIF-8@TanⅡA complete medium containing 100µg/mL were added.OD values of cells in each group were detected by MTT method at different time points(1,4,7 d),and ALP activity was detected by alkaline phosphatase(ALP)kit at different time points(1,4 d).Results The average particle size of Fe_(3)O_(4)@ZIF-8@TanⅡA was 307.12 nm,the PDI was 0.090,the potential was-40.03 mV;it was almost spherical with rough surface,the specific surface area was 337.32m^(2)/g,the magnetic saturation intensity was about 48 emu/g,and it had good superparamagnetism.The drug loading capacity of Fe_(3)O_(4)@ZIF-8@TanⅡA was 10.27%,and the encapsula-tion efficiency was 80.36%.The in vitro release behavior of Fe_(3)O_(4)@ZIF-8@TanⅡA was pH-responsive and could acceler-ate the release rate in a stimulated osteoporotic microenvironment.Compared with the control group,OD value of cells in the loading group increased after four days of administration,an

关 键 词：丹参酮ⅡA 磁性纳米粒子 沸石咪唑酯骨架材料 骨髓间充质干细胞 骨质疏松 

分 类 号：R283.6[医药卫生—中药学]