PEG-PCL 纳米胶束用于肿瘤诊断治疗的靶向成像和药物输送

doi:10.5246/jcps.2012.06.075

PEG-PCL 纳米胶束用于肿瘤诊断治疗的靶向成像和药物输送

郑华, 侯文杰, 王坚成^*, 张强

1. 北京大学医学部药学院药剂学系, 北京 100191
2. 山东绿叶制药国家重点实验室, 山东烟台 264003

收稿日期:2012-05-08 修回日期:2012-08-20 出版日期:2012-10-25 发布日期:2012-10-25
通讯作者: 王坚成*

PEG-PCL nanomicelles for cancer theranosis: targeted imaging and drug delivery

Hua Zheng, Wenjie Hou, Jiancheng Wang^*, Qiang Zhang

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State Key Laboratory of Long-acting and Targeting Drug Delivery System, LUYE PHARMA, Yantai 264003,China

Received:2012-05-08 Revised:2012-08-20 Online:2012-10-25 Published:2012-10-25
Contact: Jiancheng Wang*

摘要/Abstract

摘要： 纳米胶束, 是由疏水性内核及亲水性外壳自组装形成的纳米粒子, 利用其在肿瘤部位增强的渗透和滞留效应 (EPR效应), 已成功用作靶向药物输送载体。本研究将近红外荧光染料Cy7-NHS与NH₂-PEG-b-PCL连接合成了Cy7-PEG-PCL, 并将其组装修饰在胶束结构中, 作为紫杉醇药物的递送载体。研究结果显示, 当药物/载体比例确定为1/4, 由聚乙二醇-聚己内酯共聚物自组装形成的胶束粒径为30 nm左右, zeta电位为 -3 mV, 包封率可达95%以上。体外细胞毒实验表明, 载紫杉醇胶束对人乳腺癌MCF-7细胞增殖的抑制能力与Taxol^®制剂相似。活体成像实验结果显示Cy7标记的聚合物胶束在静脉注射后可以有效地被动靶向到肿瘤部位。另外, 以异位接种MCF-7细胞荷瘤裸鼠为模型的体内药效学实验中, 载紫杉醇聚合物胶束显示出与Taxol^®制剂相似的抗肿瘤活性。综上所述, 在肿瘤靶向成像和治疗方面, 本研究所构建的胶束载药系统显示出良好的潜力。

关键词: 胶束, 聚乙二醇-聚己内酯共聚物, 紫杉醇, 菁染料, 活体成像, 肿瘤治疗

Abstract:

Nanomicelles, self-assembling nanosized particles with a hydrophobic core and hydrophilic shell, are currently successfully used as carriers for targeted drug delivery systems via the enhanced permeability and retention (EPR) effect at the tumor sites. In this study, a near-infrared fluorescent cyanine dye (Cy7-NHS) was conjugated to poly (ethylene glycol)-block-poly (ε-caprolactone) (NH₂-PEG-b-PCL), and the resulting Cy7-PEG-PCL was further mixed with mPEG-b-PCL to form nanomicelles as carriers for paclitaxel (PTX) delivery. Our results showed that the selected mPEG₄₀₀₀-b-PCL₂₅₀₀copolymers self-assembled to form stable micelles with an average size of 30 nm in diameter and a zeta potential of approximately –3 mV. The micelles also exhibited more than 95% encapsulation efficiency of PTX when the molar ratio between paclitaxel and copolymers was 1/4. In vitro cytotoxicity study showed that the PTX-loaded nanomicelles had a similar cell growth inhibition efficacy to that of Taxol^® against human breast cancer MCF-7 cells. In vivo imaging showed that the Cy7-labeled nanomicelles could be passively targeted to tumor sites effectively after intravenous injection via the tail vein. Also, a strong anti-tumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treatment with PTX-loaded micelles, similar to that of Taxol^®. As a result, the micelle drug delivery system designed in this paper has great potential in targeted imaging of tumors and chemotherapy.

Key words: Micelles, PEG-b-PCL block copolymers, Paclitaxel, Cyanine dye, In vivo imaging, Tumor therapy

中图分类号:

R943

Supporting:

Foundation items: National Basic Research Program of China (973 Program, Grant No. 2007CB935800 and 2009CB930300), Program for New Drug R&D (Grant No. 2009ZX09310-001), NSFC projects (Grant No. 81072597), Beijing NSF project (Grant No. 7112089) and Programs from Ministry of Education (Grant No. BMU20110268 and BMU20110263).
^*Corresponding author. Tel.: 86-10-82802683

郑华, 侯文杰, 王坚成^*, 张强. PEG-PCL 纳米胶束用于肿瘤诊断治疗的靶向成像和药物输送[J]. , DOI: 10.5246/jcps.2012.06.075.

Hua Zheng, Wenjie Hou, Jiancheng Wang^*, Qiang Zhang. PEG-PCL nanomicelles for cancer theranosis: targeted imaging and drug delivery [J]. , DOI: 10.5246/jcps.2012.06.075.

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