Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24-positive cells in ovarian cancer
Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24-positive cells in ovarian cancer
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DOI：
10.3892/ol.2020.11279
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发表时间：
2020-03-01
期刊：
影响因子：
2.9
通讯作者：
Ohmichi, Masahide
中科院分区：
文献类型：
--
作者：
Ashihara, Keisuke;Terai, Yoshito;Ohmichi, Masahide
CD24在几种人类恶性肿瘤中表达上调，与上皮-间质转化（Epithelial-mesenchymal-transition， EMT）有关，具有癌症干细胞样细胞的特征，尤其是在顺铂耐药卵巢癌细胞中。药物递送系统是治疗耐药疾病的一种很有前景的治疗方法，本研究研究了一种新的cd24靶向药物递送系统用于晚期卵巢癌。我们用红色荧光物质菁氨酸5.5 （GL-CDDP-Cy5.5）制备了顺铂脂质体。为了靶向cd24阳性细胞，将抗cd24单克隆抗体修饰为上述药物（CD24-GL-CDDP-Cy5.5）。使用治疗耐药卵巢癌细胞系Caov-3细胞证实了CD24-GL-CDDP-Cy5.5的特异性摄取。CD24-GL-CDDP-Cy5.5在Caov-3异种移植小鼠体内的抗肿瘤作用。流式细胞术显示CD24-GL-CDDP-Cy5.5比GL-CDDP-Cy5.5摄取特异性更强。在异种移植小鼠中，与顺铂相比，GL-CDDP-Cy5.5和CD24-GL-CDDP-Cy5.5治疗可显著提高播散性肿瘤细胞中的铂浓度(P
CD24, which is upregulated in several human malignancies, is related to Epithelial-mesenchymal-transition (EMT) and has characteristics of cancer stem-like cells, especially in cisplatin-resistant ovarian carcinoma cells. Drug delivery systems represent a promising therapeutic approach for diseases with treatment resistance, and the present study investigated a novel CD24-targeted drug delivery system for advanced ovarian carcinoma. We produced liposomal cisplatin with a red fluorescent substance - cyanine 5.5 (GL-CDDP-Cy5.5). In order to target CD24-positive cells, an anti-CD24 monoclonal antibody was modified to the above drug (CD24-GL-CDDP-Cy5.5). Specific uptake of CD24-GL-CDDP-Cy5.5 was confirmed using a therapeutically resistant ovarian cancer cell line, Caov-3 cells. Antitumor effects of CD24-GL-CDDP-Cy5.5 were then evaluated in Caov-3 xenograft mice. CD24-GL-CDDP-Cy5.5 showed more specific uptake by flow cytometry than GL-CDDP-Cy5.5. In xenograft mice, GL-CDDP-Cy5.5 and CD24-GL-CDDP-Cy5.5 treatment had significantly higher platinum concentration in disseminated tumor cells than cisplatin (P