近红外荧光磁性复合载药脂质体的制备及应用

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FeO4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824 nm.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252.9 nm,Zeta电位为-48.6 mV,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.

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

The preparation,properties and preliminary application of near-infrared fluorescence magnetic doxorubicin-loading liposomes (DOX-NFMSLs) was studied,in which near-infrared fluorescence magnetic liposomes act as a model carrier,doxorubicin (DOX) as an entrapment drug.Fe3 O4 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 (EE％) 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 particle 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 temperature of DOX release in vitro was 41 ℃ for DOX-NFMSLs.DOX-NFMSLs had antitumor efficacy in vitro and could be real-time imaged by near-infrared fluorescent microscope (cut-off filter of 800 nm).The data showed that DOX-NFMSLs have suitable temperature 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 imaging and may aid in tumor detection as well as imaging-guided therapy.