A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells
A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells
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CD123抗体介导的新型免疫脂质体靶向急性髓系白血病细胞
DOI：
10.1016/j.ijpharm.2017.06.003
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发表时间：
2017
影响因子：
5.8
通讯作者：
Mao Shengjun
中科院分区：
文献类型：
--
作者：
Wang Yin;Liu Furong;Wang Qiantao;Xiang Honglin;Jin Hui;Li Hui;Mao Shengjun
肿瘤靶向抗体介导的免疫脂质体(ILP)的应用为治疗急性髓系白血病(AML)等恶性肿瘤提供了一种潜在的有效策略。CD123在AML细胞上特异性过表达，在细胞周期中发挥重要作用，增强细胞对凋亡刺激的抵抗力。鉴于CD123在AML细胞中的独特作用，本研究旨在利用CD123单抗开发一种新型的药物靶向递送系统。在柔红霉素(DNR)聚乙二醇化脂质体(DNR-LP)的基础上，采用插入后的方法将抗CD123单抗共价连接到脂质体表面，得到抗CD123单抗修饰的免疫脂质体(CD123-ILP)。制备了不同浓度抗CD123mAb的免疫脂质体(mAb/脂质体S100PC，摩尔比0.06%，L-CD123-ILP和H-CD123-ILP 0.14%)。流式细胞仪检测KG-1a、Kasumi-1、HL-60、NB4和THP-1细胞CD123的表达。细胞结合和摄取实验表明CD123-ILP内化到CD123+AML细胞中，而MTT法显示CD123-ILP对高表达CD123的THP-1和KG-1a细胞的生长有较强的抑制作用。此外，在体外药物释放研究中，DNR-LP和CD123-ILP在两个系统中都表现出了缓释特征，这在大鼠体内的药物动力学研究中得到了进一步的证实。在本研究中，我们首次报道了CD123-ILP的发展，为CD123+AML细胞提供了一种很有前途的药物靶向递送系统。
The application of the tumor targeting antibody-mediated immunoliposomes (ILP) provides us a potential effective strategy for treating malignancies, such as acute myeloid leukemia (AML). CD123, which is specifically overexpressed on AML cells, plays an important role in cell cycling and enhances the cell resistance to the apoptotic stimuli. Given such a unique role of CD123 in AML cells, we aim to develop a novel drug targeting delivery system using CD123 monoclonal antibody (mAb) in this study. On the basis of the daunorubicin (DNR) loaded PEGylated liposomes (DNR-LP), a post-insertion method was applied to covalently attach the anti-CD123 mAb onto the surface of the liposomes to obtain the anti-CD123 mAb modified immunoliposomes (CD123-ILP). Immunoliposomes with different anti-CD123 mAb density (mAb/liposomal S100PC, molar ratio, 0.06%, L-CD123-ILP and 0.14%, H-CD123-ILP) were prepared, respectively. The expressions of CD123 in KG-1a, Kasumi-1, HL-60, NB4 and THP-1 cells were determined by flow cytometry. The cell binding and uptake assays revealed that CD123-ILP was internalized into the CD123+AML cells, while the MTT assay indicated that CD123-ILP had stronger inhibitory effect on the growth of THP-1 and KG-1a cells, in which CD123 were highly expressed. Furthermore,in vitrodrug release studies of DNR-LP and CD123-ILP showed a sustained release profile for both systems, which were further confirmed byin vivopharmacokinetics study of liposomal DNR in rats. In this study, we reported the development of CD123-ILP for the first time by our best knowledge, which offered a promising drug targeting delivery system against CD123+AML cells.