Multifunctional core-shell nanoparticles: Discovery of previously invisible biomarkers

Davide Tamburro, Claudia Fredolini, Virginia Espina, Temple A. Douglas, Adarsh Ranganathan, Leopold Ilag, Weidong Zhou, Paul Russo, Benjamin H. Espina, Giovanni Muto, Emanuel F. Petricoin, Lance A. Liotta, Alessandra Luchini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)19178-19188
Number of pages11
JournalJournal of the American Chemical Society
Volume133
Issue number47
DOIs
StatePublished - 30 Nov 2011
Externally publishedYes

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