Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials.
Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials.
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DOI：
10.1016/j.jconrel.2015.04.036
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Jingjing Xie;Yu Gao;Rongli Zhao;P. Sinko;S. Gu;Jichuang Wang;Yuanfang Li;Yusheng Lu;Suhong Yu-Suhong
中科院分区：
文献类型：
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作者：
Jingjing Xie;Yu Gao;Rongli Zhao;P. Sinko;S. Gu;Jichuang Wang;Yuanfang Li;Yusheng Lu;Suhong Yu-Suhong
循环肿瘤细胞（CTC）已经被我们和其他人在癌症患者血液中检测到。然而，人们对如何在体内特异性捕获和灭活CTCs知之甚少，这可能会导致手术后无症状癌症幸存者成功预防转移。我们假设双抗体缀合物可能具有特异性捕获CTC的优势，优于其单抗体对应物。在这里，我们表明，表面官能化的树枝状聚合物可以依次涂覆有两种抗体，针对人结肠直肠CTC的表面生物标志物（EpCAM和Slex）。双抗体包被的树枝状聚合物在干扰血细胞的存在下，以及在八名患者的血液和施用标记的CTC的裸鼠中，与它们的单抗体包被的对应物相比，在捕获CTC方面表现出显著增强的特异性。双抗体包被的缀合物下调捕获的CTC。这项研究提供了第一个概念性证据，表明两种抗体可以生物相容地缀合到纳米材料上，以增强的特异性在体内捕获和下调CTC。
Circulating tumor cells (CTCs) have been detected by us and others in cancer patient blood. However, little is known about how to specifically capture and deactivate CTCs in vivo, which may lead to successful metastasis prevention in asymptomatic cancer survivors after surgery. We hypothesize that the dual antibody conjugates may have the advantage of capturing CTCs specifically over their single antibody counterparts. Here we show that the surface-functionalized dendrimers can be sequentially coated with two antibodies directed to surface biomarkers (EpCAM and Slex) of human colorectal CTCs. The dual antibody-coated dendrimers exhibit a significantly enhanced specificity in capturing CTCs in the presence of interfering blood cells, and in both eight-patient bloods and nude mice administered with the labeled CTCs in comparison to their single antibody-coated counterparts. The dual antibody-coated conjugates down-regulate the captured CTCs. This study provides the first conceptual evidence that two antibodies can be biocompatibly conjugated to a nanomaterial to capture and down-regulate CTCs in vivo with the enhanced specificity.