Bauhinia purprea agglutinin-modified liposomes for human prostate cancer treatment.
Bauhinia purprea agglutinin-modified liposomes for human prostate cancer treatment.
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DOI：
10.1111/cas.12839
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发表时间：
2016-01
期刊：
影响因子：
5.7
通讯作者：
Oku N
中科院分区：
文献类型：
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作者：
Ikemoto K;Shimizu K;Ohashi K;Takeuchi Y;Shimizu M;Oku N
羊蹄甲凝集素（BPA）是一种众所周知的凝集素，可识别半乳糖基糖蛋白和糖脂。在本研究中，我们首次发现BPA与人前列腺癌组织结合，而与正常前列腺组织不结合。因此，我们试图开发用于治疗前列腺癌的包封抗癌药物的BPA-PEG-修饰的脂质体（BPA-PEG-LP）。我们检查了BPA-PEG-LP与人前列腺癌DU 145细胞的肿瘤靶向性，并观察到荧光标记的BPA-PEG-LP主要通过脂质体表面BPA和细胞表面半乳糖基分子之间的相互作用与细胞结合。我们还观察到，在静脉注射给DU 145实体癌荷瘤小鼠后，BPA-PEG-LP在前列腺癌组织中积累，并与癌细胞强烈结合。在一项治疗研究中，对DU 145实体瘤荷瘤小鼠静脉注射三次包封多柔比星的BPA-PEG-LP（BPA-PEG-LPDOX，DOX剂量为2 mg/kg/天）或包封DOX的PEG修饰脂质体（PEG-LPDOX）。结果，BPA-PEG-LPDOX显著抑制了DU 145癌细胞的生长，而与DOX相同剂量的PEG-LPDOX几乎没有显示出抗癌效果。目前的研究表明，BPA‐PEG‐LP可能是一种有用的药物载体，用于治疗人类前列腺癌。
Bauhinia purprea agglutinin (BPA) is a well‐known lectin that recognizes galactosyl glycoproteins and glycolipids. In the present study, we firstly found that BPA bound to human prostate cancer specimens but not to normal prostate ones. Therefore, we sought to develop BPA‐PEG‐modified liposomes (BPA‐PEG‐LP) encapsulating anticancer drugs for the treatment of prostate cancer. We examined the tumor targetability of BPA‐PEG‐LP with human prostate cancer DU145 cells, and observed that fluorescently labeled BPA‐PEG‐LP dominantly associated with the cells via the interaction between liposome‐surface BPA and cell‐surface galactosyl molecules. We also observed that BPA‐PEG‐LP accumulated in the prostate cancer tissue after the i.v. injection to DU145 solid cancer‐bearing mice, and strongly bound to the cancer cells. In a therapeutic study, DU145 solid cancer‐bearing mice were i.v. injected thrice with BPA‐PEG‐LP encapsulating doxorubicin (BPA‐PEG‐LPDOX, 2 mg/kg/day as the DOX dosage) or PEG‐modified liposomes encapsulating DOX (PEG‐LPDOX). As a result, BPA‐PEG‐LPDOX significantly suppressed the growth of the DU145 cancer cells, whereas PEG‐LPDOX at the same dosage as DOX showed little anti‐cancer effect. The present study suggested that BPA‐PEG‐LP could be a useful drug carrier for the treatment of human prostate cancers.