CRCU

Chemical Research in Chinese Universities ›› 2011, Vol. 27 ›› Issue (4): 628-634.

• Articles • Previous Articles     Next Articles

EPR Effect of Amphiphilic Copolymer Micelles Observed by Fluorescent Imaging

LIU Tong-jun1*, LIU Shi2, HU Xiu-li2, SHENG Shi-hou1, HUANG Yu-bin2 and JING Xia-bin2*   

  1. 1. Department of Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China;
    2. State Key Laboratory of Polymer Physics and Chemistry, Changchun Institue of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
  • Received:2010-11-26 Revised:2011-03-18 Online:2011-07-25 Published:2011-06-29
  • Contact: LIU Tong-jun;JING Xia-bin E-mail:tjliu@jlu.edu.cn; xbjing@ciac.jl.cn
  • Supported by:

    Supported by the National Basic Research Program of China(No.2009CB930102) and the National High Technology    Research and Development Program of China(No. 2007AA03Z535), the National Natural Science Foundation of China(No. 21004062), the China-Japan-Korea Foresight Program(No.20621140369), “100 Talents Program” of the Chinese Academy of Sciences(No.KGCX2- YW-802) and the Project of Jilin Provincial Science & Technology Department, China(No.200705110).

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Abstract: Enhanced permeation and retention(EPR) targeting effect of rhodamine B labeled PEG-b-P(LA-co-DHP) [PEG: poly(ethylene glycol); LA: L-lactide; DHP: 2,2-dihydroxylmethyl-propylene carbonate] micelles(RhB-    micelles) was observed in H22 liver cancer bearing mice. The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P(LA-co-DHP) followed by subsequent self-assembling of the conjugate. The parent copolymer PEG-b-P(LA-co-DHP) was synthesized by ring-opening  copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc(ZnEt2) as catalyst. The micelles have a spherical shape and the average diameter is ca. 50 nm by TEM(transmission electron microscope) or 80 nm by DLS(dynamic light scattering). Their in vitro cell uptake experiment by CLSM(confocal laser scanning microscopy) and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB. The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection, free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end. But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration(fluorescent intensity) in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h, indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.

Key words: Enhanced permeability and retention(EPR) effect, Fluorescent imaging, Micelle, Passive targeting