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CREKA肽修饰的载多西他赛脂质体抗前列腺癌靶向研究
CREKA peptide-modified docetaxel loaded liposomes for targeted treatment of prostate cancer
in vitro - 第三军医大学学报 2020年42卷第21期 页码：2107-2115
- 作者机构：
1.400010 重庆，重庆医科大学附属第二医院：泌尿外科
2.400010 重庆，重庆医科大学附属第二医院：超声分子影像重庆市重点实验室
- 作者简介：
[张荣贵，E-mail: 1005983970@qq.com ZHANG Ronggui, E-mail: 1005983970@qq.com
- 基金信息：
DOI：10.16016/j.1000-5404.202005276
中图分类号： R737.25;R965;R979.1收稿：2020-05-29，
修回：2020-07-31，
纸质出版：2020-11-15
- 稿件说明：
移动端阅览
杨文波, 郝兰, 王志刚, 等. CREKA肽修饰的载多西他赛脂质体抗前列腺癌靶向研究[J]. 第三军医大学学报, 2020,42(21):2107-2115.
Wenbo YANG, Lan HAO, Zhigang WANG, et al. CREKA peptide-modified docetaxel loaded liposomes for targeted treatment of prostate cancer
in vitro [J]. Journal of Third Military Medical University, 2020, 42(21): 2107-2115.杨文波, 郝兰, 王志刚, 等. CREKA肽修饰的载多西他赛脂质体抗前列腺癌靶向研究[J]. 第三军医大学学报, 2020,42(21):2107-2115. DOI： 10.16016/j.1000-5404.202005276.
Wenbo YANG, Lan HAO, Zhigang WANG, et al. CREKA peptide-modified docetaxel loaded liposomes for targeted treatment of prostate cancer
in vitro [J]. Journal of Third Military Medical University, 2020, 42(21): 2107-2115. DOI： 10.16016/j.1000-5404.202005276.
摘要
目的
2
构建以CREKA肽修饰的包载多西他赛脂质体(CREKA-lipo-DTX)，评价该药物传递系统体外靶向性和体外抗肿瘤效应。
方法
2
首先采用迈克尔加成反应合成靶向部分DSPE-PEG2000-CREKA，随后使用薄膜水化-超声法制备CREKA-lipo-DTX并对其基本表征进行评价；将PC-3细胞和RWPE-1细胞分别分为3组(
n
=3)：空白对照组、PEG-lipo-DiI组和CREKA-PEG-DiI组，脂质体与细胞共孵育后，用激光共聚焦显微镜和流式细胞术分别对脂质体的细胞摄入进行定性和定量的分析，从而评价CREKA修饰脂质体对PC-3细胞的靶向性；将PC-3细胞分为4组(
n
=3)：空白对照组、游离DTX组、PEG-lipo-DiI组和CREKA-PEG-DiI组，通过CCK-8法和Annexin V/PI双染色法评价该药物载体对PC-3细胞的增殖抑制效应。
结果
2
成功制备出CREKA肽修饰的载药脂质体(CREKA-lipo-DTX)
其粒径为(130.37±1.44)nm，包封率为(91.93±4.64)%。该药物载体稳定性良好，体外释放结果显示其具有较好的缓释性。激光共聚焦显微镜和流式细胞术分析结果显示，与PEG-lipo-DiI组相比，PC-3细胞对CREKA修饰脂质体的摄取显著增加(
P
＜0.05)，而RWPE-1细胞对CREKA修饰脂质体的摄取差异无统计学意义(
P
>
0.05)；体外抗肿瘤实验结果显示，与游离DTX组和PEG-lipo-DTX组相比，CREKA-lipo-DTX组增强了多西他赛对PC-3细胞的杀伤作用(
P
＜0.05)，而且使PC-3细胞早期凋亡和晚期凋亡的数量均显著增加(
P
＜0.05)。
结论
2
成功制备出一种具有长循环和肿瘤特异靶向特性的高效低毒的脂质体载药系统，体外可以特异靶向于PC-3细胞，提高了该载体的体外抗肿瘤效应。
Abstract
Objective
2
To prepare CREKA peptide-modified docetaxel (DTX) loaded liposomes (CREKA-lipo-DTX) and to evaluate their targeted binding ability and anti-proliferative activity
in vitro
.
Methods
2
Firstly
Michael addition reaction was used to synthesize the targeted part DSPE-PEG2000-CREKA
and then CREKA-lipo-DTX was prepared by thin film hydration-ultrasound method
and its basic characterization was evaluated. Both PC-3 cells and RWPE-1 cells were divided into 3 groups respectively (
n
=3): blank control group
PEG-lipo-DiI group and CREKA-lipo-DiI group. After co-incubation with the cells
the cellular uptake of liposomes was analyzed qualitatively and quantitatively by laser confocal microscopy and flow cytometry respectively
so as to evaluate the targeting effect of CREKA modified vector on PC-3 cells. The cellular uptake of liposomes was analyzed qualitatively and quantitatively by laser confocal microscopy and flow cytometry respectively. The anti-proliferative activity of CREKA-lipo-DTX was evaluated by CCK-8 assay and Annexin V-PI apoptosis detection kit on blank control group
free DTX group
PEG-lipo-DiI group and CREKA-PEG-DiI group of PC-3 cells.
Results
2
CREKA-lipo-DTX was successfully prepared
with an average particle size of 130.37±1.44 nm
and encapsulation rate of (91.93±4.64)%. The obtained drug carrier had good stability and showed good slow-release behavior
in vitro
. The results of laser confocal microscopy and flow cytometry analysis indicated that the uptake of CREKA-modified liposomes by PC-3 cells was significantly increased (
P
<
0.05) when compared with the unmodified liposome group (PEG-lipo-DiI)
while no such difference was seen in RWPE-1 cells (
P
>
0.05).
In vitro
anti-tumor experimental results suggested that enhanced killing effect of DTX on PC-3 cells and significantly increased numbers of early and late apopto
tic PC-3 cells were observed in the CREKA-lipo-DTX group when compared with the free DTX and PEG-lipo -DTX groups (
P
<
0.05).
Conclusion
2
A high-efficiency and low-toxicity lipoid drug delivery system with long cycle and tumor specific targeting characteristics has been successfully prepared
which can specifically target PC-3 cells
in vitro
and thus can improve the anti-tumor effect of the carrier
in vitro
.
关键词
Keywords
references
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