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Udukala et al. J Cancer Metastasis Treat 2020;6:25 Journal of Cancer
DOI: 10.20517/2394-4722.2020.45 Metastasis and Treatment

Original Article Open Access

Early detection of non-small cell lung cancer in
liquid biopsies by ultrasensitive protease activity

analysis

Dinusha N. Udukala , Sebastian O. Wendel 1,2,# , Hongwang Wang , Asanka S. Yapa , Obdulia Covarrubias-
1,#
1
1
Zambrano , Katharine Janik , Gary Gadbury , Deryl L. Troyer , Stefan H. Bossmann 1
2
1
1
3
1 Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA.
2 Department of Statistics, Kansas State University, Manhattan, KS 66506, USA.
3 Department of Anatomy & Physiology, Kansas State University, Manhattan, KS 66506, USA.
# Authors contributed equally.
Correspondence to: Prof. Stefan H. Bossmann, Department of Chemistry, 201 CBC Building, Kansas State University, Manhattan,
KS 66506, USA. E-mail: sbossman@ksu.edu
How to cite this article: Udukala DN, Wendel SO, Wang H, Yapa AS, Covarrubias-Zambrano O, Janik K, Gadbury G, Troyer
DL, Bossmann SH. Early detection of non-small cell lung cancer in liquid biopsies by ultrasensitive protease activity analysis. J
Cancer Metastasis Treat 2020;6:25. http://dx.doi.org/10.20517/2394-4722.2020.45

Received: 12 May 2020 First Decision: 23 Jun 2020 Revised: 3 Jul 2020 Accepted: 14 Jul 2020 Published: 7 Aug 2020
Academic Editor: Wei Zhang Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: A significant fraction of mortalities from non-small cell lung cancer could be prevented, if the cancer would
be diagnosed earlier. Nanobiosensors for the ultrasensitive detection of active proteases in serum were designed
to detect a significant protease activity signature of non-small cell lung cancer (stage I and higher).

Methods: We determined the activity of nine protease biomarkers in the sera of non-small cell lung cancer
patients and compared them with the protease activities of a control group of healthy human subjects using
optical nanobiosensors. They consist of a central Fe/Fe 3 O 4 core/shell nanoparticle with an attached Fluorescence
resonance energy transfer-pair [tetrakis-carboxyphenyl porphyrin (TCPP) and cyanine 5.5]. TCPP is attached
to the central nanoparticle via a protease-cleavable tether, whereas cyanine 5.5 is tethered permanently to the
dopamine-layer surrounding the nanoparticle.

Results: Based on the activity pattern of urokinase plasminogen activator, matrix metalloproteinases 1, 2, 3, 7, 9,
and 13, and cathepsins B and L as well, non-small cell lung cancer could be detected at stage I by means of a liquid
biopsy.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
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