Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and imaging

被引:85
作者
Tsai, Hsieh-Chih [1 ]
Chang, Wei-Hsiang [1 ]
Lo, Chun-Liang [3 ]
Tsai, Cheng-Hung [1 ]
Chang, Che-Hau [1 ]
Ou, Ta-Wei [4 ]
Yen, Tzu-Chen [5 ,6 ]
Hsiue, Ging-Ho [1 ,2 ]
机构
[1] Natl Tsing Hua Univ, Dept Chem Engn, Hsinchu 300, Taiwan
[2] Chung Yuan Christian Univ, R&D Ctr Membrane Technol, Dept Chem Engn, Chungli 320, Taiwan
[3] Natl Yang Ming Univ, Dept Biomed Engn, Taipei 112, Taiwan
[4] Natl Cent Univ, Dept Chem Engn, Tao Yuan 320, Taiwan
[5] Chang Gung Med Hosp & Univ, Dept Nucl Med, Tao Yuan 333, Taiwan
[6] Chang Gung Med Hosp & Univ, Mol Image Ctr, Tao Yuan 333, Taiwan
关键词
Micelles; Drug delivery; Biocompatibility; Copolymer; In vivo test; INTRACELLULAR DRUG-DELIVERY; POLYMERIC MICELLE; KB-CELLS; IN-VIVO; FOLATE; PH; NANOPARTICLES; AGENTS; ADRIAMYCIN; SYSTEM;
D O I
10.1016/j.biomaterials.2009.11.059
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g-PLA and diblock copolymer PEG-PLA with functional moiety was developed in this study. The mixed micelles had well defined core shell structure which was evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA exhibited pH stimulate to enable intracellular drug delivery and outer shell of PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate for cancer specific targeting were synthesized at the end of the polymer chain. The graft and diblock copolymer self assembled to nanospheres against water with an average diameter below 120 nm without doxorubicin, and an average diameter of around 200 nm when loaded with drug. From drug released study, a change in pH destroy the inner core to lead a significant doxorubicin(Dox) release from mixed micelles. Cellular uptake of folate-micelles was found to be higher than that of non-folate-micelles due to the folate-binding effect on the cell membrane, thereby providing a similar cytotoxic effect to drug only against the HeLa cell line. In vivo study revealed that specific targeting of folate-micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate-PEG-PLA have great potential in cancer chemotherapy and diagnosis. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2293 / 2301
页数:9
相关论文
共 31 条
[1]   Ligand-targeted therapeutics in anticancer therapy [J].
Allen, TM .
NATURE REVIEWS CANCER, 2002, 2 (10) :750-763
[2]  
ANTONSEN KP, 1993, BIOMAT ARTIF CELL IM, V21, P1
[3]  
Bae Y, 2005, MOL BIOSYST, V1, P242, DOI 10.1039/b500266d
[4]   In vivo antitumor activity of the folate-conjugated pH-Sensitive polymeric micelle selectively releasing adriamycin in the intracellular acidic compartments [J].
Bae, Younsoo ;
Nishiyama, Nobuhiro ;
Kataoka, Kazunori .
BIOCONJUGATE CHEMISTRY, 2007, 18 (04) :1131-1139
[5]   Multifunctional polymeric nanoparticles from diverse bioactive agents [J].
Bertin, PA ;
Gibbs, JM ;
Shen, CKF ;
Thaxton, CS ;
Russin, WA ;
Mirkin, CA ;
Nguyen, ST .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (13) :4168-4169
[6]  
DI DA, 1997, NEPHRON, V76, P192
[7]   Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates [J].
Dubé, D ;
Francis, M ;
Leroux, JC ;
Winnik, FM .
BIOCONJUGATE CHEMISTRY, 2002, 13 (03) :685-692
[8]  
ELWOOD PC, 1989, J BIOL CHEM, V264, P14893
[9]   Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment [J].
Hobbs, SK ;
Monsky, WL ;
Yuan, F ;
Roberts, WG ;
Griffith, L ;
Torchilin, VP ;
Jain, RK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4607-4612
[10]   Folate functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs [J].
Hong, Guobin ;
Yuan, Renxu ;
Liang, Biling ;
Shen, Jun ;
Yang, Xiaoqiang ;
Shuai, Xintao .
BIOMEDICAL MICRODEVICES, 2008, 10 (05) :693-700