PEG-PCLnanomicelles for cancer theranosis:targeted imaging and drug delivery  

PEG-PCL 纳米胶束用于肿瘤诊断治疗的靶向成像和药物输送(英文)

作　　者：郑华[1] 侯文杰[1] 王坚成[1,2] 张强[1] 

机构地区：[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

出　　处：《Journal of Chinese Pharmaceutical Sciences》2012年第6期591-597,共7页中国药学（英文版）

基　　金：National Basic Research Program of China (973Program,Grant No. 2007CB935800 and 2009CB930300);Program forNew Drug R&D (Grant No. 2009ZX09310-001);NSFC projects(Grant No. 81072597);Beijing NSF project (Grant No. 7112089);Programs from Ministry of Education (Grant No. BMU20110268and BMU20110263)

摘　　要：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）（NH 2-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 mPEG 4000-b-PCL 2500 copolymers 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.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：Micelles PEG-b-PCL block copolymers PACLITAXEL Cyanine dye In vivo imaging Tumor therapy 

分 类 号：TB383[一般工业技术—材料科学与工程] R730.5[医药卫生—肿瘤]