Probing Intracellular Biomarkers and Mediators of Cell Activation Using Nanosensors and Bioorthogonal Chemistry

Nanomaterials offer unique physical properties that make them ideal biosensors for scant cell populations. However, specific targeting of nanoparticles to intracellular proteins has been challenging. Here, we describe a technique to improve intracellular biomarker sensing using nanoparticles that is...

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Bibliographic Details
Published inACS nano Vol. 5; no. 4; pp. 3204 - 3213
Main Authors Haun, Jered B, Devaraj, Neal K, Marinelli, Brett S, Lee, Hakho, Weissleder, Ralph
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 26.04.2011
Subjects
Biomarkers - analysis
Cell Division
Cell Line, Tumor
Cell Survival
Humans
Nanoparticles
Nuclear Magnetic Resonance, Biomolecular
Proteins - analysis
targeting
nanoparticles
bioorthogonal chemistry
cancer
intracellular
tetrazine
diagnostic magnetic resonance
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Summary:Nanomaterials offer unique physical properties that make them ideal biosensors for scant cell populations. However, specific targeting of nanoparticles to intracellular proteins has been challenging. Here, we describe a technique to improve intracellular biomarker sensing using nanoparticles that is based on bioorthogonal chemistry. Using trans-cyclooctene-modified affinity ligands that are administered to semipermeabilized cells and revealed by cycloaddition reaction with tetrazine-conjugated nanoparticles, we demonstrate site-specific amplification of nanomaterial binding. We also show that this technique is capable of sensing protein biomarkers and phosho-protein signal mediators, both within the cytosol and nucleus, via magnetic or fluorescent modalities. We expect the described method will have broad applications in nanomaterial-based diagnostics and therapeutics.
ISSN:1936-0851
1936-086X
DOI:10.1021/nn200333m