Multifunctional Core–Shell Nanoparticles: Discovery of Previously Invisible Biomarkers

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,...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of the American Chemical Society Vol. 133; no. 47; pp. 19178 - 19188
Main Authors:	Tamburro, Davide, Fredolini, Claudia, Espina, Virginia, Douglas, Temple A, Ranganathan, Adarsh, Ilag, Leopold, Zhou, Weidong, Russo, Paul, Espina, Benjamin H, Muto, Giovanni, Petricoin, Emanuel F, Liotta, Lance A, Luchini, Alessandra
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 30-11-2011
Subjects:	Acrylamides - chemical synthesis Acrylamides - chemistry Biomarkers, Tumor - blood Biomarkers, Tumor - chemistry Coloring Agents - chemistry Growth Hormone - urine Humans Hydrogel, Polyethylene Glycol Dimethacrylate - chemical synthesis Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry Molecular Structure Nanoparticles - chemistry Particle Size Peptides - chemistry Polymers - chemical synthesis Polymers - chemistry Porosity Proteins - chemistry Surface Properties
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0002-7863 1520-5126 1520-5126
DOI:	10.1021/ja207515j