首页> 外文会议>2014 40th Annual Northeast Bioengineering Conference >Differentially charged nanomaterials control selectin-mediated adhesion and isolation of cancer cells and leukocytes under flow
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Differentially charged nanomaterials control selectin-mediated adhesion and isolation of cancer cells and leukocytes under flow

机译:带电荷的纳米材料可控制选择素介导的流动下癌细胞和白细胞的粘附和分离

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The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Biomimetic flow devices hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, we developed surfaces of nanoscale roughness and varying surface charge for E-selectin mediated adhesion and separation of cancer cells and leukocytes from flow. Halloysite nanotubes (HNTs) functionalized with the negatively charged surfactant sodium dodecanoate (NaL) significantly increased the number of colon and breast cancer cells captured from flow. Conversely, HNT functionalization with the positively charged surfactant decyl trimethyl ammonium bromide (DTAB) abrogated nearly all cancer cell adhesion to E-selectin (ES). The opposite trend was observed with leukocytes, with decreased cell adhesion to E-selectin on NaL-functionalized HNTs, and increased adhesion to DTAB-functionalized HNTs. This work reveals that differentially charged nanomaterials can control receptor-mediated cancer cell and leukocyte adhesion, enabling new approaches to increase the number and purity of separated CTCs from patient blood.
机译:癌细胞从原发肿瘤向远处转移的转移导致源自多个器官的癌症的预后不良。越来越多的证据表明,循环肿瘤细胞(CTC)与微血管内皮细胞之间基于选择蛋白的黏附与转移性传播有关,其方式类似于炎症过程中的白细胞黏附。利用抗体和选择素介导的相互作用在流动下捕获细胞,仿生流动装置有望成为一种诊断工具,可以分离四氯化碳并潜在地治疗转移。但是,CTC和白细胞都具有选择素配体这一事实对高纯度捕集提出了挑战。在这里,我们开发了纳米级粗糙度和E-选择蛋白介导的粘附力以及从流动中分离癌细胞和白细胞的表面电荷变化的表面。用带负电荷的表面活性剂十二烷酸钠(NaL)官能化的埃洛石纳米管(HNT)显着增加了从流动中捕获的结肠和乳腺癌细胞的数量。相反,用带正电荷的表面活性剂癸基三甲基溴化铵(DTAB)进行的HNT功能化几乎消除了所有癌细胞对E-选择素(ES)的粘附。白细胞观察到相反的趋势,细胞对NaL功能化的HNTs对E-选择蛋白的粘附减少,对DTAB功能化的HNTs的粘附增加。这项工作表明,带电荷的纳米材料可以控制受体介导的癌细胞和白细胞的粘附,从而使新方法能够增加从患者血液中分离出的四氯化碳的数量和纯度。

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