近红外荧光磁性复合载药脂质体的制备及应用

Preparation and Application of Near-infrared Fluorescence Magnetic Doxorubicin-loading Liposomes

拟建立以近红外荧光磁性复合脂质体(NFMSLs)为模型药物载体、盐酸多柔比星(DOX)为包封药物的药物输送系统,研究了近红外荧光磁性载药复合脂质体(DOX-NFMSLs)的制备、性质及初步应用。采用共沉淀法制备Fe3O4磁流体,CdTe掺杂Se制备近红外量子点CdSeTe,薄膜分散法制备DOX-NFMSLs。用DOX荧光分光光度法测定DOX-NFMSLs的包封率和体外药物释放率;用DOX-NFMSLs与HepG2肝癌细胞共孵育来进行细胞成像和细胞毒性实验。结果表明,近红外CdSeTe量子点粒径约为5nm,闪锌矿结构,发射波长824nm。磷脂与胆固醇质量比为8∶1,药脂比为1∶20的DOX-NFMSLs平均粒径为252.9nm,Zeta电位为-48.6mV,理想释放药物温度为41℃,平均包封率为(74.84±0.89)%。DOX-NFMSLs对HepG2肝癌细胞有一定的抗癌效果。得到了具有良好磁响应、释药温度T=41℃、可近红外成像的载药脂质体。

The preparation, properties and preliminary application of near-infrared fluorescence magnetic doxorubicin-loading liposomes （LX-NFMSLs） was studied, in which near-infrared fluorescence magnetic liposomes act as a model carrier, doxorubicin （DOX） as an entrapment drug. Fe3O4 magnetic fluid was prepared by using co-precipitation method. The near-infrared CdSeTe quantum dots （CdSeTe QDs） were prepared by incorporating selenium ions into CdTe nanocrystals. DOX-NFMSLs were prepared by the thin-film dispersion method. Fluorescence spectrophotometry was used to examine the drug content, entrapment efficiency （EEl） and in vitro drug release of DOX-NMSLs. The killer activity of HepG2 cells and fluorescent imaging were detected by cytotoxicity test and cell imaging experiments. The CdSeTe QDs had a zinc-blende crystal structure with emission at 824 nm, and an average par- ticle size of about 5 nm The mean particle size of DOX-NFMSLs was 252. 9 nm, the Zeta potential was -48. 6 mV and they had near-infrared fluorescent emission （815 nm）. The optimum recipe for preparation of DOX-NFMSLs was founded as.. liposome/Chol ratio 8 ： 1 （m/m）, DOX/liposome ratio 1 ： 20 （m/m）, with which the product＇s EE% was （74. 84±0. 89）%. The optimal tempera- ture of DOX release in vitro was 41℃ for DOX-NFMSLs. DOX-NFMSLs had antitumor efficacy in vitro and could be real-time ima- ged by near-infrared fluorescent microscope （cut-off filter of 800 nm）. The data showed that DOX-NFMSLs have suitable tempera- ture of DOX release （T=41 ℃）, good near-infrared fluorescence and magnetic property. After incubation with HepG2 cells, they realized near-infrared imaging and produced an anti-cancer effect. So DOX-NFMSLs open up new perspectives for near-infrared ima- ging and may aid in tumor detection as well as imaging-guided therapy.