Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer
Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer
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DOI：
10.1016/j.jconrel.2011.10.010
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发表时间：
2012-06-10
影响因子：
10.8
通讯作者：
Minamino, Tetsuo
中科院分区：
文献类型：
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作者：
Nishikawa, Kaoru;Asai, Tomohiro;Minamino, Tetsuo
肝素结合表皮生长因子样生长因子（HB-EGF）的表达增加在某些癌症如卵巢癌和乳腺癌中经常被观察到，这种蛋白是药物递送系统（DDS）给药的理想靶点。在本研究中，我们开发了靶向HB-EGF的新型免疫脂质体用于癌症治疗。与与野生型Vero细胞的结合相比，免疫脂质体与过表达HB-EGF的Vero- h细胞显著相关，而未经抗体修饰的脂质体与两种类型的细胞均不相关。此外，免疫脂质体在Vero-H细胞和MDA-MB-231人乳腺癌细胞中的摄取增强，后者已知高表达HB-EGF。这些结果表明HB-EGF介导了表达HB-EGF的细胞中免疫脂质体的结合和摄取。接下来，我们测定了包封抗癌药物的免疫脂质体对荷瘤小鼠的治疗效果。为此，我们制备了多柔比星（DOX）包裹的免疫脂质体，并将其静脉注射到携带MDA-MB-231癌细胞的小鼠体内。结果，这些dox包封的免疫脂质体不仅抑制肿瘤进展，而且抑制肿瘤消退。总之，我们的研究结果表明，抗hb - egf抗体修饰的脂质体可能是一种有效的DDS载体，用于治疗表达hb - egf的癌症。(C) 2011 Elsevier b.v.版权所有
Increased expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) is frequently observed in certain cancers such as ovarian and breast cancers, and this protein is a desirable target for drug delivery by a drug delivery system (DDS). In the present study, we developed novel immunoliposomes targeting HB-EGF for cancer therapy. The immunoliposomes significantly associated with Vero-H cells overexpressing HB-EGF compared with their binding to wild-type Vero cells, whereas liposomes without modification by the antibody did not associate with either type of cells. Moreover, enhanced uptake of the immunoliposomes into Vero-H cells was observed as well as that into MDA-MB-231 human breast cancer cells, which are known to highly express HB-EGF. These results suggest that HB-EGF mediates the binding and uptake of the immunoliposomes in HB-EGF-expressing cells. Next, we determined the therapeutic effect of these immunoliposomes encapsulating an anticancer drug on tumor-bearing mice. For this purpose, we prepared doxorubicin (DOX)-encapsulated immunoliposomes and injected them intravenously into mice bearing MDA-MB-231 cancer cells. As a result, these DOX-encapsulated immunoliposomes suppressed not only tumor progression but also tumor regression. In conclusion, our results indicate that anti-HB-EGF antibody-modified liposomes could be a useful DDS carrier for the treatment of HB-EGF-expressing cancers. (C) 2011 Elsevier B. V. All rights reserved.