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Disease detection by ultrasensitive quantification of microdosed synthetic urinary biomarkers.

ABSTRACT: The delivery of exogenous agents can enable noninvasive disease monitoring, but existing low-dose approaches require complex infrastructure. In this paper, we describe a microdose-scale injectable formulation of nanoparticles that interrogate the activity of thrombin, a key regulator of clotting, and produce urinary reporters of disease state. We establish a customized single molecule detection assay that enables urinary discrimination of thromboembolic disease in mice using doses of the nanoparticulate diagnostic agents that fall under regulatory guidelines for "microdosing."

SUBMITTER: Warren AD

PROVIDER: S-EPMC4183649 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Disease detection by ultrasensitive quantification of microdosed synthetic urinary biomarkers.

Warren Andrew D AD Gaylord Shonda T ST Ngan Kevin C KC Dumont Milutinovic Milena M Kwong Gabriel A GA Bhatia Sangeeta N SN Walt David R DR

Journal of the American Chemical Society 20140923 39

The delivery of exogenous agents can enable noninvasive disease monitoring, but existing low-dose approaches require complex infrastructure. In this paper, we describe a microdose-scale injectable formulation of nanoparticles that interrogate the activity of thrombin, a key regulator of clotting, and produce urinary reporters of disease state. We establish a customized single molecule detection assay that enables urinary discrimination of thromboembolic disease in mice using doses of the nanopar ...[more]

PMID: 25198059

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Project description:Background and study aims Bowel cancer is diagnosed in 40,000 people each year in the UK. Early detection and treatment of bowel cancer is important as it improves survival. This has led to a “fast-track” system to speed up waiting times and access to hospital tests. Deciding who to test is a hard for GPs and hospital doctors because bowel symptoms are common and are not usually due to cancer. In addition, not all people with a bowel cancer develop symptoms. Therefore, at present the vast majority of patients are required to undergo testing. An internal camera examination of the large bowel (colonoscopy) is the best way to look at the large bowel. This is invasive, can be uncomfortable and needs strong laxatives to prepare the bowel. There is a risk of unplanned admission to hospital and surgery. This test is also expensive and the demand is increasing in the NHS. In the UK, 300,000 people a year are referred through the fast-track system for suspected bowel cancer. Over 90% of these have normal results, meaning they have undergone unpleasant testing that did not help them. It is now possible to look at natural chemicals, produced by normal bacteria that live in everybody’s bowel, to help diagnose bowel conditions. Bowel cancer alters the chemical “signature”. The aim of this study is to test the urine of 600 people referred by their GP to the fast-track pathway for these chemicals to see how good they are at predicting bowel cancer. Who can participate? Patients aged 18 and over, referred by their GP for fast-track assessment due to symptoms of colorectal cancer What does the study involve? Participants provide a urine sample when they attend the hospital for colonoscopy or CT scanning. Participants are also asked to complete a short questionnaire collecting demographic information and some data about lifestyle including smoking status, alcohol use and dietary habit (meat eating, vegetarian or vegan diet). From that point on their clinical pathway is unaffected by participation in the study and the results of the volatile compound testing are not be available to the clinical team. At the end of their investigations (maximum of 63 days), a member of the research team accesses patient notes to collect disease outcome data coded as cancer, polyp or normal. The participants receive treatment as normal judged on the clinical data available to the clinicians caring for them. The urine samples are sent for analysis at the University of the West of England. They are analysed using three separate machines to identify which of these machines is the best for use in a clinical setting, to take forward into a larger study. Data from the testing are then analysed along with the data about disease status in order to assess the sensitivity and reliability of the testing for the identification of patients at high risk of having colon cancer.

Dataset Information

Disease detection by ultrasensitive quantification of microdosed synthetic urinary biomarkers.

Publications

Disease detection by ultrasensitive quantification of microdosed synthetic urinary biomarkers.

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