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细胞穿膜肽PFV修饰紫杉醇/青蒿琥酯共载靶向胶束的制备及体
外抗肿瘤作用研究 Δ
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王 为 ，李学涛 ，孔 亮 ，姜 爽 ，罗一夫 ，王晓波 （1.辽宁中医药大学药学院，辽宁 大连 116600；2.解
放军联勤保障部队第九六七医院药物研究所，辽宁 大连 116011）
中图分类号 R94 文献标志码 A 文章编号 1001-0408（2020）21-2592-06
DOI 10.6039/j.issn.1001-0408.2020.21.06
摘 要 目的：制备细胞穿膜肽PFV修饰紫杉醇（PTX）/青蒿琥酯（ART）共载靶向胶束，并考察其体外抗肿瘤活性。方法：按前期
优化的工艺，采用薄膜水化法制备PFV修饰PTX/ART共载靶向胶束，并对其进行表征。以空白胶束作为空白对照，采用磺基罗丹
明B法评价PTX胶束、ART胶束、PTX/ART胶束以及PFV修饰PTX/ART共载靶向胶束对人胃癌BGC-823细胞的毒性；以香豆素
作为荧光探针取代PTX，制成相应的不同胶束，采用流式细胞仪和荧光显微镜测定和观察BGC-823细胞对各胶束的摄取情况和
靶向性；并通过Transwell小室法考察PTX胶束、ART胶束、PTX/ART胶束以及PFV修饰PTX/ART共载靶向胶束对BGC-823细胞
侵袭的影响。结果：PFV 修饰 PTX/ART 共载靶向胶束的平均粒径为（51.30±3.95）nm，分散系数为 0.19±0.01，Zeta 电位为
（0.21±0.02）mV，PTX、ART 的包封率均高于 90％，形态呈圆球形。空白胶束对 BGC-823 细胞无明显毒性，PTX 胶束、PTX/ART
胶束以及 PFV 修饰 PTX/ART 共载靶向胶束对 BGC-823 细胞的半数抑制浓度分别为（3.09±0.22）、（1.93±0.24）、（1.11±0.15）
μmol/L；不同胶束在BGC-823细胞核中的分布数量排序依次为PFV修饰香豆素/ART胶束＞香豆素/ART胶束＞香豆素胶束＞空
白对照，抑制细胞侵袭作用的大小依次为 PFV 修饰 PTX/ART 共载靶向胶束＞PTX/ART 胶束＞ART 胶束＞PTX 胶束＞空白对
照。结论：制备的PFV修饰PTX/ART共载靶向胶束符合《中国药典》要求；其对BGC-823细胞具有较强的细胞毒性，可提高药物的
靶向性和细胞对药物的摄取能力，并能抑制肿瘤细胞的侵袭和转移。
关键词 细胞穿膜肽；紫杉醇；青蒿琥酯；胶束；人胃癌BGC-823细胞；靶向作用；抗肿瘤作用
Study on Preparation and in vitro Anticancer Activity of Cell Penetrating Peptide PFV-modified Paclitaxel/
artesunate Co-loaded Targeting Micelles
WANG Wei ，LI Xuetao ，KONG Liang ，JIANG Shuang ，LUO Yifu ，WANG Xiaobo （1. School of Pharmacy，
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Liaoning University of TCM，Liaoning Dalian 116600，China；2. No.967 Hospital of the Joint Logistic Support
Force of PLA，Liaoning Dalian 116011，China）
ABSTRACT OBJECTIVE：To prepare cell penetrating peptide PFV-modified paclitaxel（PTX）/artesunate（ART）co-loaded
targeting micelles，and to investigate in vitro anti-tumor activity. METHODS：According to optimal technology，PFV-modified PTX/
ART co-loaded targeting micelles were prepared by membrane hydration method，and were characterized. Using blank micelle as
blank control，sulforhodamine B （SRB） method was used to evaluate the toxicity of PTX micelles，ART micelles，PTX/ART
micelles and PFV-modified PTX/ART co-loaded targeting micelles to human gastric cancer BGC-823 cells. The coumarin was used
as fluorescent probe replacing PTX to prepare corresponding micelles. Then，the uptake of BGC-823 cells to corresponding micelles
and targeting effect were observed and determined by flow cytometry and fluorescence microscope. The effects of PTX micelles，
ART micelles，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles on the invasion of BGC-823 cells were
investigated by Transwell chamber method. RESULTS：Average particle size of PFV-modified PTX/ART co-loaded targeting
micelles was（51.30±3.95）nm；PDI was 0.19±0.01，and Zeta potential was（0.21±0.02）mV. The encapsulation efficiency of
PTX and ART were higher than 90％ . The shape of micelles were spherical. The blank micelles had no obvious toxicity to
BGC-823 cells. The IC50 value of PTX micelles，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to
BGC-823 cells were（3.09±0.22），（1.93±0.24），（1.11±0.15）μmol/L，respectively. The distribution amount of different micelles
in BGC-823 cell nucleus in the descending order were PFV-modified coumarin/ART micelles＞coumarin/ART micelles＞coumarin
micelles＞blank control. The order of inhibitory effect was PFV-modified PTX/ART co-loaded targeting micelles＞PTX/ART
micelles＞ART micelles＞PTX micelles＞blank control.
Δ 基 金 项 目 ：国 家 自 然 科 学 基 金 资 助 项 目（No.81973462，
CONCLUSIONS： Prepared PFV-modified PTX/ART
No.81874347）
co-loaded targeting micelles are in line with the quality of
＊ 硕 士 研 究 生 。 研 究 方 向 ：药 物 新 型 给 药 系 统 。 E-mail：
1915286446@qq.com Chinese Pharmacopoeia. It shows strong cytotoxicity to
# 通信作者：教授，博士生导师，博士。研究方向：药物新型给药 BGC-823 cells，can improve the drug targeting and the cell
系统。E-mail：wxbbenson0653@sina.com uptake，and inhibit the invasion and metastasis of BGC-823
·2592 · China Pharmacy 2020 Vol. 31 No. 21 中国药房 2020年第31卷第21期
