Preparation of vincristine loaded low density lipoprotein nanoparticles modified by T7 peptide and evaluation of therapeutic effect on glioma
10.16438/j.0513-4870.2017-1108
- VernacularTitle:T7肽修饰的载长春新碱低密度脂蛋白纳米粒的制备及脑胶质瘤靶向性和治疗作用评价
- Author:
Yue ZHANG
1
;
Yang YANG
2
;
Mei-fang ZHAI
2
;
Zhi-jiang CHEN
1
;
Lin CUI
2
;
Shi-yao FU
2
;
Fang-lin YU
2
;
Zhi-ping LI
2
;
Xing-guo MEI
1
Author Information
1. School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China
2. Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
low density lipoprotein;
peptide;
vincristine;
target;
glioma
- From:
Acta Pharmaceutica Sinica
2018;53(3):460-466
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this study was to prepare T7 peptide modified vincristine loaded low density lipoprotein (T7-LDL-VCR) nanoparticles to penetrate through blood brain barrier for targeting the brain tumor cells. Firstly, the low density lipoprotein (LDL) nanoparticles were extracted and separated from human serum by density gradient centrifugation method, and then was loaded into the nanoparticle's lipid core by the dry film method, T7 peptide was covalent modified on the surface of the nanoparticles. T7-LDL-VCR was characterized by particle size, entrapment efficiency and peptide attachment efficiency. The fluorescent probe DiR was used to track the brain biodistribution of T7-LDL-VCR in mice bearing intracranial C6 glioma by means of in vivo imaging. The therapeutic effect of nanoparticles was observed with magnetic resonance imaging (MRI). Finally, relative tumor volume and survival curve were determined in mice. The results showed that the mean size of the prepared T7-LDL-VCR nanoparticle was about 30 nm, encapsulation efficiency was 30.1%, and peptide attachment efficiency was 63.88%. As expected, the prepared preparation has good brain targeting and good effect on the treatment of glioma in mice:the relative tumor volumes of T7-VCR-LDL, LDL-VCR and VCR were 30%, 51.50% and 79.25%, respectively; the median survival time (36 days), which was 2, 1.85 and 1.38 fold higher than that of physiological saline, free VCR and LDL-VCR, respectively. This study suggests that dual modified hposomes possessed a better ability penetrating the blood brain barrier to target the brain tumor with significant antitumor activities.
