多功能纳米红细胞载药体系构建及其光热／光动力效应  

Preparation of multifunctional nanoscaled red blood cells drug delivery system and its photothermal and photodynamic effects

作　　者：陈伯玮[1] 史澍睿 万国运 王银松[1] 张连云[2] 王悦[2] Chen Bowei;Shi Shurui;Wan Guoyun;Wang Yinsong;Zhang Lianyun;Wang Yue(School of Pharmacy, Tianjin Medical University, Tianjin 300070, Chin;Stomatological Hospital, Tianjin Medical University, Tianjin 300070, Chin)

机构地区：[1]天津医科大学药学院,300070 [2]天津医科大学口腔医院,300070

出　　处：《国际生物医学工程杂志》2018年第1期32-37,共6页International Journal of Biomedical Engineering

基　　金：国家自然科学基金（81572655,81573005）;天津医科大学“十三五综投”研究生创新基金（YJSCx201713）

摘　　要：目的 制备一种基于红细胞的多功能纳米载药体系，研究其体外光热及光动力效应。 方法 通过挤出法制备吲哚菁绿（ICG）/阿霉素（DOX）共载纳米红细胞（DIRAs），并测定其形态、粒径、包封率及稳定性等参数；采用粒径电位测定仪研究其升温产气导致的粒径变化；通过红外热成像仪考察其体外光热效应；采用激光共聚焦显微镜研究乳腺癌4T1细胞对DIRAs的摄取情况；利用2 ＇，7 ＇-二氯荧光黄双乙酸盐（DCFH-DA）荧光探针及激光共聚焦显微镜考察光动力效应。 结果 成功制备了DIRAs，其形态规则均匀，平均粒径（97.0±20.1） nm，Zeta电位约-21.6 mV，ICG和DOX的包封率分别为93.5%和95.2%，28 d内稳定性良好。该纳米载药体系可以产生与游离ICG相同的体外光热效应。经激光照射后，DIRAs显著增强了4T1细胞对药物的摄取，且增强了光动力效应。 结论 制备的DIRAs纳米载药体系形态规则，粒径适宜，具有较高的包封率及光热转化效率,可增强4T1细胞对药物的摄取及光动力效应，有望用于联合光热/光动力和化疗对乳腺癌的治疗。Objective To prepare a red blood cells based multifunctional nanoscaled drug delivery system,and to study its in vitro photothermal and photodynamic effects.Methods The indocyanine green（ICG）/doxorubicin（DOX）co-loaded nanoscaled red blood cells（DIRAs）were prepared using an extrusion method.The morphology,particle size,encapsulation efficiency,and stability were determined.The heating related change of particle size was studied using a size and potential tester.The in vitro photothermal effect was studied using an infrared imaging device.The uptake of DIRAs to 4T1 cells was studied using a CLSM examination.The in vitro photodynamic effect was studied using a fluorescence probe and CLSM examination.Results DIRAs were successfully prepared with a uniform and homogeneous size which was about（97.0±20.1）nm.The Zeta potential was about-21.6 mV and the encapsulation efficiency of ICG and DOX were 93.5% and 95.2%,respectively.The DIRAs had excellent stability within 28 days.This nanoscaled drug delivery system had identical photothermal effect compared to free ICG.The cellular uptake of DOX was significantly improved after the laser irradiation and the photodynamic effect was enhanced.Conclusions The prepared DIRAs have regular shape,suitable particle size,high encapsulation efficiency and high photothermal conversion efficiency.DIRAs can improve the cellular uptake of DOX and enhance the photodynamic efficiency.This biomimetic multifunctional nano-system could facilitate breast cancer treatment by combining PTT/PDT and chemotherapy.

关 键 词：纳米红细胞 吲哚菁绿 阿霉素 联合治疗 乳腺癌 

分 类 号：R730.5[医药卫生—肿瘤] R737.9[医药卫生—临床医学]