铁蛋白-普鲁士蓝纳米复合材料的制备及在肿瘤光热治疗中的应用研究

Preparation of ferritin-Prussian blue nanocomposite and its application in tumor photothermal therapy

目的建立铁蛋白-普鲁士蓝纳米材料(ferritin-PB NPs)的制备方法,并探究其光热转换性能和对肿瘤细胞的光热杀伤效果。方法首先通过沉淀法制备普鲁士蓝纳米材料(PB NPs),随后负载于铁蛋白空腔结构中,构建得到ferritin-PB NPs。采用红外光谱和紫外可见分光光谱测试ferritin-PB NPs中的成分组成,采用动态光散射仪和透射电子显微镜测试ferritin-PB NPs的尺寸及形貌,通过热成像仪测试ferritin-PB NPs的光热升温效果及光热稳定性效果,通过激光共聚焦显微镜观察ferritin-PB NPs在HeLa细胞和HepG2细胞中的摄取效果,并通过MTT实验测试ferritin-PB NPs对HeLa细胞的光热杀伤效果。结果ferritin-PB NPs的形貌为铁蛋白内部包覆PB NPs的复合结构,可响应730 nm激光辐照迅速将光能转化为热能,导致测试溶液温度明显升高。ferritin-PB NPs能迅速被HeLa细胞和HepG2细胞摄取,并且在730 nm光照条件下抑制HeLa细胞的增殖。结论通过简便的方法制备了ferritin-PB NPs,具有良好的生物相容性和光热细胞毒性效果,后期有望用于体内肿瘤治疗。

Objective To establish a method for preparing ferritin-Prussian blue nanocomposites(ferritin-PB NPs)and evaluate their photothermal conversion performance and photothermally responsive tumor cell killing effect.Methods Prussian blue nanomaterials were prepared by the precipitation method and then loaded into the ferritin cavity to construct ferritin-PB NPs.The composition of ferritin-PB NPs was tested by infrared spectroscopy and UV-vis absorption spectroscopy.The size and morphology of ferritin-PB NPs were measured by dynamic light scattering and transmission electron microscopy.The photothermal heating effect and photothermal stability effect of the ferritin-PB NPs material were tested by a thermal imager.The uptake effect of ferritin-PB NPs in HeLa and HepG2 tumor cells was observed by laser confocal microscopy.The photothermal killing effect of ferritin-PB NPs on HeLa tumor cells was tested by the MTT assay.Results The morphology of the ferritin-PB NPs is a composite structure of ferritin coated with PB NPs,which can rapidly convert light energy into heat energy in response to 730 nm laser irradiation,resulting in a significant increase in the temperature of the test solution.The ferritin-PB NPs were rapidly taken up by HeLa and HepG2 tumor cells and significantly inhibited the proliferation of HeLa cells under 730 nm light irradiation.Conclusions The ferritin-PB NPs were obtained by a simple preparation method,which has good biocompatibility and photothermal cytotoxicity and is expected to be used for in vivo tumor therapy in the extended research.