Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles

被引:123
作者
Peng, Cheng-Liang [1 ,2 ]
Lai, Ping-Shan [3 ]
Lin, Fen-Huei [1 ,2 ]
Wu, Steven Yueh-Hsiu [1 ,2 ]
Shieh, Ming-Jium [1 ,2 ,4 ,5 ]
机构
[1] Natl Taiwan Univ, Coll Med, Inst Biomed Engn, Taipei 100, Taiwan
[2] Natl Taiwan Univ, Coll Engn, Taipei 100, Taiwan
[3] Natl Chung Hsing Univ, Dept Chem, Taichung 402, Taiwan
[4] Natl Taiwan Univ Hosp, Dept Oncol, Taipei 100, Taiwan
[5] Coll Med, Taipei 100, Taiwan
关键词
Star-shaped copolymer; Micelle; Photodynamic therapy; SN-38; Chemotherapy; Colon cancer; ENDOTHELIAL GROWTH-FACTOR; POLYAMIDOAMINE DENDRIMER CONJUGATION; METASTATIC COLORECTAL-CANCER; POLYION COMPLEX MICELLES; CELL LUNG-CANCER; POLYMERIC MICELLES; PHOTOCHEMICAL INTERNALIZATION; PHARMACOKINETIC TRIAL; TOPOISOMERASE-I; PHASE-I;
D O I
10.1016/j.biomaterials.2009.03.048
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form micelles, which act as nanosized photosensitizing agents for photodynamic therapy (PDT) and further encapsulate hydrophobic drugs. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer. In this study, SN-38 encapsulated CSBC micelles were successfully prepared using a lyophilization-hydration method. Our results show that the prolonged plasma residence time of SN-38/CSBC micelles as compared with free CPT-11 permit increased tumor accumulation and consequently, improved antitumor activity. The combined effects of SN-38/CSBC micelles with PDT were evaluated in an HT-29 human colon cancer xenograft model. Interesting, SN-38/CSBC-mediated PDT synergistically inhibited tumor growth, resulting in up to 60% complete regression of well-established tumors after 3 treatments. These treatments also decreased the microvessel density (MVD) and cell proliferation within the subcutaneous tumors. Therefore, this SN-38/CBSC delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3614 / 3625
页数:12
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