CD133-targeted SN38 mPEG-PCL/mal-PEG-PCL micelles for human colorectal cancer stem cell therapy

• Main Authors: Sin-Tzu Ning, 寗欣慈
• Other Authors: Ming-Jium Shieh
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/35974076911061790222

碩士 === 國立臺灣大學 === 醫學工程學研究所 === 102 === Cancer stem-like cells play key role in tumor development and these cells is relevant to the failure of conventional chemotherapy. To achieve a favorable therapy of colorectal cancer, amphiphilic polymer ethylene-glycol-ε-caprolactone (mPEG-PCL) and maleimide-ethylene-glycol-ε-caprolactone (mal-PEG-PCL) is fabricated and may self-assemble to form micelle which possesses well biological compatibility as a topoisomerases inhibitor, SN38 nanocarrier. For cancer stem cell therapy, CD133 (prominin-1) is a putative cancer stem-like cells (CSLCs) maker for colorectal cancer and is suggested to be a therapeutic target. Overexpression of CD133 has demonstrated enhanced tumor initiating ability and tumor relapse probability. To resolve the problems of chemotherapy failure, SN38 loaded micelles was conjugated CD133 antibody for targeting CD133+ cells. In this study, CD133 antibody-conjugated SN38 loaded nanoparticles (CD133Ab-NPs-SN38) were efficiently binding to HCT116 cells, which overexpression of CD133 glycoprotein. In cytotoxic effect, CD133Ab-NPs- SN38 was more than non-targeted mixed nanoparticles (NPs-SN38) in HCT116 cells. Furthermore, CD133Ab-NPs-SN38 could target to CD133+ cells and inhibits colony formation compare to NPs-SN38. In vivo studies in HCT116 xenograft model revealed that CD133Ab-NPs-SN38 depresses tumor growth and retard recurrence. Immuno- histochemistry image showed that reduction of CD133 expression when treated with CD133Ab-NPs-SN38. Therefore, this CD133-targeted nanoparticles delivery system could killing CD133 positive cells and has potential to offer cancer stem cell therapy.