Breast cancer is generally asymptomatic at early stages of the disease. Current state of the art screening tools such as mammography and breast examination miss early breast cancers due to the absence of mass lesions, are ineffective in detecting cancer in young women, and require invasive biopsy. New methods are needed to complement current methods for the detection and prognosis of precancerous and cancerous breast lesions while they are small and more easily treated. The analysis of the secreted glycoantigens, protein antigens and non-coding microRNAs (miRNA) in nipple aspirate fluid represents a very promising approach able to detect cancer-related biomarkers directly in body fluids mirroring the breast tissue-specific tumor microenvironment. Our long term goal is to develop a simple, sensitive and robust detection platform for diagnosing diseases at an asymptomatic early stage. Our diagnostic platform is based on the elegant and elaborate protein channel of a biological motor. We have inserted the motor channel into a lipid bilayer and the resulting system exhibits robust properties and generates extremely sensitive, stable and reproducible conductance signatures when analytes interact with the channel. We further demonstrated its utility as a highly sensitive device for detection of cancer-associated proteins i presence of many contaminants at single molecule level. The short-term goal of this proposal is to develop this motor channel as a nanopore for high-throughput single molecule detection of glyco-antigen, protein antigen and miRNA biomarkers extracted from breast cancer patient nipple aspirate fluid. The platform consists of: a membrane-embedded motor channel serving as a highly sensitive nanopore; programmable probes for capturing breast cancer associated antigens; and ultra-sensitive electrophysiological setup for multiplexed high-throughput single molecule detection. Incorporating our device into routine practice will enable physicians to monitor cellular changes within breast ducts earlier, before they develop into larger, potentially cancerous lesions.

Public Health Relevance

We have recently developed a robust single pore diagnostic platform based on the motor channel of a biological motor for detection of analytes with high sensitivity and specificity. Herein, the motor channel will be engineered to harbor programmable probes for multiplexed high-throughput single molecule detection of glyco- antigen, protein antigen and miRNA biomarkers extracted from breast cancer patients. This platform will enable diagnosis of breast cancer at early stages where it is treatable.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
2R01EB012135-07
Application #
9106837
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Lash, Tiffani Bailey
Project Start
2010-10-01
Project End
2020-02-29
Budget Start
2016-05-01
Budget End
2017-02-28
Support Year
7
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Ohio State University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Haque, Farzin; Zhang, Hui; Wang, Shaoying et al. (2018) Methods for Single-Molecule Sensing and Detection Using Bacteriophage Phi29 DNA Packaging Motor. Methods Mol Biol 1805:423-450
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Zhao, Zhengyi; Zhang, Hui; Shu, Dan et al. (2017) Construction of Asymmetrical Hexameric Biomimetic Motors with Continuous Single-Directional Motion by Sequential Coordination. Small 13:
Haque, Farzin; Wang, Shaoying; Wu, Taoxiang et al. (2017) Advances in nanopore sensing promises to transform healthcare. Nanomedicine (Lond) 12:1907-1909
Wang, Shaoying; Zhou, Zhi; Zhao, Zhengyi et al. (2017) Channel of viral DNA packaging motor for real time kinetic analysis of peptide oxidation states. Biomaterials 126:10-17
Wang, Shaoying; Ji, Zhouxiang; Yan, Erfu et al. (2017) Three-step channel conformational changes common to DNA packaging motors of bacterial viruses T3, T4, SPP1, and Phi29. Virology 500:285-291
Pi, Fengmei; Zhao, Zhengyi; Chelikani, Venkata et al. (2016) Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism. J Virol 90:8036-46
Ji, Zhouxiang; Wang, Shaoying; Zhao, Zhengyi et al. (2016) Fingerprinting of Peptides with a Large Channel of Bacteriophage Phi29 DNA Packaging Motor. Small 12:4572-8
Pi, Fengmei; Vieweger, Mario; Zhao, Zhengyi et al. (2016) Discovery of a new method for potent drug development using power function of stoichiometry of homomeric biocomplexes or biological nanomotors. Expert Opin Drug Deliv 13:23-36

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