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Multifunctional Cor...
Multifunctional Core-Shell Nanoparticles : Discovery of Previously Invisible Biomarkers
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- Tamburro, Davide (författare)
- Stockholms universitet,Institutionen för analytisk kemi
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- Fredolini, Claudia (författare)
- Stockholms universitet,Institutionen för analytisk kemi
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Espina, Virginia (författare)
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Douglas, Temple A. (författare)
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Ranganathan, Adarsh (författare)
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- Ilag, Leopold (författare)
- Stockholms universitet,Institutionen för analytisk kemi
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Zhou, Weidong (författare)
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Russo, Paul (författare)
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Espina, Benjamin H. (författare)
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Muto, Giovanni (författare)
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Petricoin, Emanuel F., III (författare)
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Liotta, Lance A. (författare)
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Luchini, Alessandra (författare)
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(creator_code:org_t)
- 2011-11-03
- 2011
- Engelska.
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 133:47, s. 19178-19188
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Many low-abundance biomarkers for early detection of cancer and other diseases are invisible to mass spectrometry because they exist in body fluids in very low concentrations, are masked by high-abundance proteins such as albumin and immunoglobulins, and are very labile. To overcome these barriers, we created porous, buoyant, core-shell hydrogel nanoparticles containing novel high affinity reactive chemical baits for protein and peptide harvesting, concentration, and preservation in body fluids. Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles were functionalized with amino-containing dyes via zero-length cross-linking amidation reactions. Nanoparticles functionalized in the core with 17 different (12 chemically novel) molecular baits showed preferential high affinities (K(D) < 10(-11) M) for specific low-abundance protein analytes. A poly(N-isopropylacrylamide-co-vinylsulfonic acid) shell was added to the core particles. This shell chemistry selectively prevented unwanted entry of all size peptides derived from albumin without hindering the penetration of non-albumin small proteins and peptides. Proteins and peptides entered the core to be captured with high affinity by baits immobilized in the core. Nanoparticles effectively protected interleukin-6 from enzymatic degradation in sweat and increased the effective detection sensitivity of human growth hormone in human urine using multiple reaction monitoring analysis. Used in whole blood as a one-step, in-solution preprocessing step, the nanoparticles greatly enriched the concentration of low-molecular weight proteins and peptides while excluding albumin and other proteins above 30 kDa; this achieved a 10,000-fold effective amplification of the analyte concentration, enabling mass spectrometry (MS) discovery of candidate biomarkers that were previously undetectable.
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Tamburro, Davide
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Fredolini, Claud ...
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Espina, Virginia
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Douglas, Temple ...
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Ranganathan, Ada ...
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Ilag, Leopold
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visa fler...
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Zhou, Weidong
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Russo, Paul
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Espina, Benjamin ...
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Muto, Giovanni
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Petricoin, Emanu ...
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Liotta, Lance A.
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Luchini, Alessan ...
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visa färre...
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Stockholms universitet