Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody
Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody
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DOI：
10.1016/j.biomaterials.2013.07.067
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发表时间：
2013-11-01
期刊：
影响因子：
14
通讯作者：
Shieh, Ming-Jium
中科院分区：
文献类型：
--
作者：
Lee, Pei-Chi;Chiou, Yu-Chi;Shieh, Ming-Jium
本研究利用单壁碳纳米管（SWNTs）结合抗体C225实现对EGFR过表达的结直肠癌细胞的靶向治疗。此外，还对化疗药物7-乙基-10-羟基喜树碱（SN 38）的控释进行了研究。我们使用了三种不同的结直肠癌细胞系，HCT 116，HT 29和SW 620，按EGFR表达水平降低的顺序列出。我们的结果表明，SWNT可以使用C225特异性结合EGER表达的细胞。EGFR过表达细胞（HCT 116和HT 29）对SWNT的摄取明显高于阴性对照（SW 620）。接下来，我们证明了受体介导的内吞作用是SWNT进入细胞的主要途径。结果，释放了大量的SN 38，并杀死了EGFR过表达的细胞。利用人羧酸酯酶（hCE）在细胞质中破坏SN 38与SWNT载体之间的键，研究了药物的控制释放过程。通过共聚焦显微镜观察到的细胞内SN 38释放显示SN 38实际上首先从SWNT载体解离。SN 38进入细胞核，而SWNT载体仍留在细胞质中。总之，这些数据表明，单壁碳纳米管是一个很好的载体靶向控制释放治疗。(C)2013爱思唯尔有限公司保留所有权利。
In this study, single-walled carbon nanotubes (SWNTs) conjugated with antibody C225 were used to achieve targeted therapy against EGFR over-expressed colorectal cancer cells. In addition, the control release of the chemotherapeutic drug, 7-Ethyl-10-hydroxy-camptothecin (SN38), was studied. We used three different colorectal cancer cell lines, HCT116, HT29, and SW620, listed in the order of decreasing expression levels of EGFR. Our results showed that SWNT could use C225 to specifically bind to EGER-expressed cells. The cellular uptakes of SWNT of EGFR over-expressed cells (HCT116 and HT29) were much higher than that of the negative control (SW620). We, next, demonstrated that receptor-mediated endocytosis was the primary cell entry route for SWNT. As a consequence, abundant amount of SN38 was released and EGFR over-expressed cells were killed. The drug control release process was studied by utilizing human carboxylesterase enzyme (hCE) that would break the bond linking SN38 and SWNT-carrier in cytoplasm. The intracellular SN38 release observed by confocal microscopy showed that SN38 actually dissociated from the SWNT-carrier first. SN38's entry to nucleus was then followed while the SWNT-carrier still remained in the cytoplasm. Overall, all these data suggested that SWNT could be a good carrier for targeting controlled release therapy. (C) 2013 Elsevier Ltd. All rights reserved.