title: 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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, USA.
authors.forename: Jered B
authors.initials: JB
authors.lastname: Haun
authors.forename: Neal K
authors.initials: NK
authors.lastname: Devaraj
authors.forename: Brett S
authors.initials: BS
authors.lastname: Marinelli
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D053758:Nanoparticles; D019906:Nuclear Magnetic Resonance, Biomolecular; D011506:Proteins / Q000032:analysis
chemical_list: D015415:Biomarkers; D011506:Proteins