CD44细胞
单克隆抗体
阿霉素
癌症研究
流式细胞术
化学
靶向治疗
医学
药理学
治疗指标
脂质体
癌症
抗体
体外
免疫学
化疗
内科学
药品
生物化学
作者
Leila Arabi,Ali Badiee,Fatemeh Mosaffa,Mahmoud Reza Jaafari
标识
DOI:10.1016/j.jconrel.2015.10.044
摘要
Although liposomes improve the safety and pharmacokinetic properties of free drugs, they have not sufficiently enhanced the therapeutic efficacy compared to them. To address this problem, targeted therapy of tumor cells holds great promise to further enhance therapeutic index and decreases off-target effects compared with non-targeted liposomes. In the context of antibody-mediated targeted cancer therapy, we evaluated the anti-tumor activity and therapeutic efficacy of Doxil, and that of Doxil modified with a monoclonal antibody (mAb) against CD44, which is one of the most well-known surface markers associated with Cancer Stem Cells (CSCs). Flow cytometry analyses and confocal laser scanning microscopy results showed significant enhanced cellular uptake of CD44-targeted Doxil (CD44-Doxil) in CD44-positive C-26 cells compared to Doxil. However, CD44-negative NIH-3T3 cells showed a similar uptake and in vitro cytotoxicity with both CD44-Doxil and non-targeted Doxil. In BALB/c mice bearing C-26 murine carcinoma, CD44-Doxil groups exhibited significantly higher doxorubicin concentration (than Doxil) inside the tumor cells, while their circulation time and distribution profile remained comparable. CD44-Doxil at doses of either 10 or 15 mg/kg resulted in superior tumor growth inhibition and higher inclination to tumor, indicating the potential of anti-CD44 mAb targeting in therapeutic efficacy improvement. This study provides proof-of-principle for actively tumor-targeting concept and merits further investigations.
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