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Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology 
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2010 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 2, no 4, 504-518 p.Article in journal (Refereed) Published
Abstract [en]

Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology

Place, publisher, year, edition, pages
2010. Vol. 2, no 4, 504-518 p.
Keyword [en]
Peptidome; Cancer; Biomarker; Nanoparticle; Mass spectrometry
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-56870DOI: 10.1208/s12248-010-9211-3OAI: oai:DiVA.org:su-56870DiVA: diva2:413516
Available from: 2011-04-28 Created: 2011-04-28 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Colloidal/Solid Phase Extraction (C/S PE) Methods Based on Hydrogel Nanoparticles, Titanium dioxide microparticles and Empore Membranes Applied to Biological and Environmental Matrices
Open this publication in new window or tab >>Colloidal/Solid Phase Extraction (C/S PE) Methods Based on Hydrogel Nanoparticles, Titanium dioxide microparticles and Empore Membranes Applied to Biological and Environmental Matrices
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of the work described in this thesis was to create and develop novel technologies in order to overcome barriers and hurdles that analytical chemistry faces focusing on sample extraction. In paper I dye containing amine groups (e.g. Acid Black 48, Remazol Brilliant Blue R) were coupled to NIPA/Acrylic acid (AAc) particles by condensation of the amine group and the carboxylic group. The high affinity between dyes and proteins allow for fast kinetics and complete depletion of the supernatant and protection of the captured analyte from enzymatic degradation. The ability of particles to capture and concentrate analytes was tested against a panel of low abundance, labile tumor relevant biomarkers and in serum. Results indicate that the nanoparticles increased the sensitivity limit of mass spectrometry analysis and that the dye based baits have extremely high affinity for the target analytes so that particles capture all the analyte present in solution. Biomarker harvesting nanoparticles may be useful for discovery of novel diagnostic analytes, can increase the sensitivity of detection for analytical methods such as immunoassays and MS, and protect labile biomarkers from degradation during collection, shipment and storage. In paper II and paper III, applications of hydrogel nanoparticles to serum samples from cancer patients are reported. Hydrogel nanoparticles were integrated in a mass spectrometry based workflow for the discovery of candidate biomarkers. Lists of candidate biomarkers were identified that are under verification and validation. In paper IV and V hydrogel nanoparticles functionalized with dyes, were employed to increase the sensitivity of diagnostic test for Lyme disease and to detect human growth hormone (hGH) in urine samples. In paper VI, titanium dioxide (TiO2) microparticles were used to pack fused silica capillary column and used to capture and enrich phosphopeptides in vitreous samples. In paper VII, Empore disk membranes were used to capture organophosphates (OPEs) flame retardant from air samples. Empore disk membranes were used as on- line extraction followed by reverse phase liquid chromatography tandem mass spectrometry (RPLC-MS/MS) analysis. Optimized “geometry” settings were used to strip semi volatile and volatile compounds from C8 membrane. This novel design allowed for a better analyte focusing in the HPLC column, reduced the volume of the organic solvent employed for the extraction and the analysis time, and eliminated sample contamination, and loss of analyte.

Place, publisher, year, edition, pages
Stockholm: Department of Analytical Chemistry, Stockholms University, 2011. 110 p.
Keyword
biomarkers, nanogels, solid-phase extraction, organophosphate esters, peptides, mass spectrometry
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-56873 (URN)978-91-7447-231-8 (ISBN)
Public defence
2011-06-01, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
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Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Manuscript. Paper 6: Manuscript.Available from: 2011-05-10 Created: 2011-04-28 Last updated: 2011-05-02Bibliographically approved

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