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Probing intracellular biomarkers and mediators of cell activation using nanosensors and bioorthogonal chemistry.

ABSTRACT: 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.

SUBMITTER: Haun JB

PROVIDER: S-EPMC3088084 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Probing intracellular biomarkers and mediators of cell activation using nanosensors and bioorthogonal chemistry.

Haun Jered B JB Devaraj Neal K NK Marinelli Brett S BS Lee Hakho H Weissleder Ralph R

ACS nano 20110308 4

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 n ...[more]

PMID: 21351804

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