Immunoavidity-Based Capture of Tumor Exosomes Using Poly(amidoamine) Dendrimer Surfaces
Immunoavidity-Based Capture of Tumor Exosomes Using Poly(amidoamine) Dendrimer Surfaces
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DOI：
10.1021/acs.nanolett.0c00950
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发表时间：
2020-08-12
期刊：
影响因子：
10.8
通讯作者：
Hong, Seungpyo
中科院分区：
文献类型：
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作者：
Poellmann, Michael J.;Nair, Ashita;Hong, Seungpyo
肿瘤来源的血液循环外泌体作为一种生物标志物具有极大改善癌症治疗的潜力。然而，有效地分离外泌体仍然是一个巨大的技术挑战。本研究提出了一种新型的纳米结构聚合物表面，通过强贪婪性高效捕获外泌体。使用从肿瘤细胞系中分离的外泌体测试了各种表面结构，包括多价树状大分子、PEG和肿瘤靶向抗体。我们发现双层树突结构在捕获加入人血清的培养外泌体时表现出最高的效率。重要的是，优化后的表面从头颈癌患者血浆样本中捕获的肿瘤外泌体数量是健康供体的4倍。原子力显微镜的纳米力学分析也表明，这种增强是由于树状大分子介导的多价结合（亲合力）和增强的短程粘附。我们的研究结果支持树突表面以高灵敏度和特异性检测肿瘤外泌体，显示其作为新的癌症液体活检平台的潜力。
Tumor-derived blood-circulating exosomes have potential as a biomarker to greatly improve cancer treatment. However, effective isolation of exosomes remains a tremendous technical challenge. This study presents a novel nanostructured polymer surface for highly effective capture of exosomes through strong avidity. Various surface configurations, consisting of multivalent dendrimers, PEG, and tumor-targeting antibodies, were tested using exosomes isolated from tumor cell lines. We found that a dual layer dendrimer configuration exhibited the highest efficiency in capturing cultured exosomes spiked into human serum. Importantly, the optimized surface captured a > 4-fold greater amount of tumor exosomes from head and neck cancer patient plasma samples than that from healthy donors. Nanomechanical analysis using atomic force microscopy also revealed that the enhancement was attributed to multivalent binding (avidity) and augmented short-range adhesion mediated by dendrimers. Our results support that the dendrimer surface detects tumor exosomes at high sensitivity and specificity, demonstrating its potential as a new cancer liquid biopsy platform.