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Immunoavidity-Based Capture of Tumor Exosomes Using Poly(amidoamine) Dendrimer Surfaces

May 14, 2020
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Abstract

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.

Enhanced immunoavidity capture through dendrimer-mediated multivalent and short range interactions

Published

Nano Letters
Nano Letters Volume 20 Issue 8 journal cover

Cited by

This article is cited by 16 publications

  1. Poellmann, M. J., Bu, J., Liu, S., Wang, A. Z., Seyedin, S. N., Chandrasekharan, C., Hong, H., Kim, Y., Caster, J. M., & Hong, S. (2023). Nanotechnology and machine learning enable circulating tumor cells as a reliable biomarker for radiotherapy responses of gastrointestinal cancer patients. Biosensors & bioelectronics, 226, 115117. https://doi.org/10.1016/j.bios.2023.115117
  2. Yin, Y., Han, X., Li, C., Sun, T., Li, K., Liu, X., & Liu, M. (2022). The status of industrialization and development of exosomes as a drug delivery system: A review. Frontiers in pharmacology, 13, 961127. https://doi.org/10.3389/fphar.2022.961127
  3. Poellmann, M. J., Rawding, P., Kim, D., Bu, J., Kim, Y., & Hong, S. (2022). Branched, dendritic, and hyperbranched polymers in liquid biopsy device design. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 14(3), e1770. https://doi.org/10.1002/wnan.1770
  4. Lee, T., Rawding, P. A., Bu, J., Hyun, S., Rou, W., Jeon, H., Kim, S., Lee, B., Kubiatowicz, L. J., Kim, D., Hong, S., & Eun, H. (2022). Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC). Cancers, 14(9), 2061. https://doi.org/10.3390/cancers14092061
  5. Rawding, P. A., Bu, J., Wang, J., Kim, D. W., Drelich, A. J., Kim, Y., & Hong, S. (2022). Dendrimers for cancer immunotherapy: Avidity-based drug delivery vehicles for effective anti-tumor immune response. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology, 14(2), e1752. https://doi.org/10.1002/wnan.1752