Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.
Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.
Nano Lett. 2020 Aug 12;20(8):5686-5692. doi: 10.1021/acs.nanolett.0c00950. Epub 2020 May 19.
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.
肿瘤来源的血循环外泌体有望成为一种极大改善癌症治疗的生物标志物。然而，外泌体的有效分离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化聚合物表面，通过强亲和性实现外泌体的高效捕获。使用从肿瘤细胞系中分离的外泌体，对各种表面构型（包含多价树状大分子、PEG 和肿瘤靶向抗体）进行了测试。我们发现，双层树状大分子构型在捕获培养的外泌体方面表现出最高的效率，这些外泌体被掺入人血清中。重要的是，与健康供体相比，优化后的表面从头颈癌患者的血浆样本中捕获的肿瘤外泌体数量增加了 4 倍以上。原子力显微镜的纳米力学分析也表明，这种增强归因于多价结合（亲合力）和树状大分子介导的短程粘附的增强。我们的研究结果支持该树状大分子表面具有高灵敏度和特异性地检测肿瘤外泌体的能力，表明其作为一种新的癌症液体活检平台具有潜力。
