磁导向性光敏药物载体的制备及其阿糖胞苷释放效果的研究

Preparation of Site-specific Smart Nanocomposites for Drug Delivery and Study on Light-Controlled Cytarabine Release Performance

目的制备具有磁导向性的智能药物载体,初步研究其生物毒性及其对阿糖胞苷的控释效果。方法通过高压水热反应合成出具有超顺磁性的纳米核心-Fe_3O_4球,进一步于磁核外部包裹MCM-41分子筛以形成核-壳结构;在MCM-41分子筛孔道内连接"门控"分子4,5-二氮杂芴-9-酮(DAFO),从而获得具有大比表面积、良好承载能力的智能药物载体。结果本实验所制备得到的纳米Fe_3O_4球直径为280 nm,经SiO_2、MCM-41分子筛包覆、门控分子修饰后粒径增至540 nm左右。利用透射电镜(TEM)、扫描电镜(SEM)以及N_2吸附/解吸法等手段对载体的结构与吸附能力进行了测试;运用MTT法对载体细胞毒性进行了检测,并以阿糖胞苷为实验药物进行了初步体外控释效果分析。结论所得药物载体无细胞毒性,可在外加磁场下向所需部位聚集,并在特定波长光线照射下通过门控分子构型翻转释放出药物分子,从而实现磁导向性智能控释。

OBJECTIVE To prepare smart & site-specific drug carrier for controlled release purpose and study the bio-compatibilities and release performance.METHODS By using high pressure thermo-heat method in autoclave, superparamagnetic core was obtained and further coated by SiO2 and MCM-41, therefore the “core-shell” structure was formed. To make the carrier “smart” and thus responsive to stimuli which was light in this research, the tunnels of the molecular sieve were grafted with gating molecules, 4,5-diazafluoren-9-one (indicated in the paper as DAFO). For bio-compatibilities testing, MTT in-vitro experiment was conducted. Cytarabine was used as test drug to preliminarily evaluate the controlled release performance of the drug carrier in vitro.RESULTS The Fe3O4 nano-particles synthesized via high-pressure hydro-thermo procedure exhibited superparamagnetic with mean diameter of 280 nm. After SiO2 & molecular sieve coating steps and ligand grafting steps, the particles grew to 540 nm. The sub-structure of the carrier was confirmed by scanning/transmission electron microscope(SEM & TEM) and nitrogen adsorption/desorption. Our “smart” carrier was able to be guided to the sites or organs with magnetic field and more importantly it was able to unload drug molecules under 510 nm light irritation that could flip the gating-molecule. Furthermore, the drug carrier illustrated bio-compatibility and showed obvious cytotoxicity.CONCLUSION The novel nanocomposites developed in this study can be used as targeted drug carrier.