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Nano Pom-poms Prepared Highly Specific Extracellular Vesicles Expand the Detectable Cancer Biomarkers

Nan He, Sirisha Thippabhotla, Cuncong Zhong, Zachary Greenberg, Liang Xu, Ziyan Pessetto, Andrew K. Godwin, Yong Zeng, Mei He
doi: https://doi.org/10.1101/2021.02.21.432188
Nan He
1Department of Chemical and Petroleum Engineering, Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA
2Clara Biotech Inc., Lawrence, KS 66047, USA
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Sirisha Thippabhotla
3Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS 66045, USA
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Cuncong Zhong
3Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS 66045, USA
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Zachary Greenberg
4Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
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Liang Xu
5Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA
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Ziyan Pessetto
6Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Andrew K. Godwin
6Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
7University of Kansas Cancer Center, Kansas City, KS 66160, USA
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Yong Zeng
8Department of Chemistry, University of Florida, Gainesville, FL 32603, USA
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Mei He
1Department of Chemical and Petroleum Engineering, Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA
4Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
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  • For correspondence: mhe@cop.ufl.edu
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Abstract

Extracellular vesicles (EVs), particularly exosomes, are emerging biomarker sources. However, due to heterogeneous populations secreted from diverse cell types, mapping EV multi-omic molecular information specifically to their pathogenesis origin for cancer biomarker identification is still extraordinary challenging. Herein, we introduced a novel 3D-structured nanographene immunomagnetic particles (NanoPoms) with unique flower pom-poms morphology and photo-click chemistry for specific marker-defined capture and release of intact small EVs. This specific EV isolation approach leads to the expanded identification of targetable cancer biomarkers with enhanced specificity and sensitivity, as demonstrated by multi-omic EV analysis of bladder cancer patient tissue fluids using the next generation sequencing of somatic DNA mutations, miRNAs, and the global proteome. The NanoPoms prepared sEVs also exhibit distinctive in vivo biodistribution patterns, highlighting the highly viable and integral quality. The developed method is simple and straightforward, and is applicable to nearly all types of biological fluids and amenable for scale up and high-throughput EV isolation.

Competing Interest Statement

Related to this research, the author M.H. has patent application: Methods for generative therapeutic delivery platform (PCT/US2019/057237) and is licensed by Clara Biotech Inc. All other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 22, 2021.
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Nano Pom-poms Prepared Highly Specific Extracellular Vesicles Expand the Detectable Cancer Biomarkers
Nan He, Sirisha Thippabhotla, Cuncong Zhong, Zachary Greenberg, Liang Xu, Ziyan Pessetto, Andrew K. Godwin, Yong Zeng, Mei He
bioRxiv 2021.02.21.432188; doi: https://doi.org/10.1101/2021.02.21.432188
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Nano Pom-poms Prepared Highly Specific Extracellular Vesicles Expand the Detectable Cancer Biomarkers
Nan He, Sirisha Thippabhotla, Cuncong Zhong, Zachary Greenberg, Liang Xu, Ziyan Pessetto, Andrew K. Godwin, Yong Zeng, Mei He
bioRxiv 2021.02.21.432188; doi: https://doi.org/10.1101/2021.02.21.432188

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