Self-assembling nanoprobes that display off/on 19F nuclear magnetic resonance signals for protein detection and imaging.

Magnetic resonance imaging (MRI) is one of the most promising techniques for the non-invasive visualization of biomarkers and biologically relevant species, both in vivo and ex vivo. Although (1)H MRI with paramagnetic contrast agents, such as Gd(3+) complexes and iron oxide, is widely used, it often suffers from low contrast because of the large background signals caused by the abundant distribution of protons in biological samples. Here we report the use of supramolecular organic nanoparticles to detect specific proteins by (19)F-based MRI in an off/on mode. In NMR spectroscopy these designed probes are silent when aggregated, but in the presence of a target protein they disassemble to produce a sharp signal. This 'turn-on' response allowed us to visualize clearly the protein within live cells by (19)F MRI and construct an in-cell inhibitor assay. This recognition-driven disassembly of nanoprobes for a turn-on (19)F signal is unprecedented and may extend the use of (19)F MRI for specific protein imaging.

[1]  B Morgenstern,et al.  Contrast agents and applications to assess tumor angiogenesis in vivo by magnetic resonance imaging. , 2007, Current medicinal chemistry.

[2]  Vikram D Kodibagkar,et al.  19F: a versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. , 2005, Current medicinal chemistry.

[3]  U. Dürr,et al.  Solid state 19F NMR parameters of fluorine-labeled amino acids. Part I: aromatic substituents. , 2008, Journal of magnetic resonance.

[4]  K. Hofmann,et al.  Hormone-receptor studies with avidin and biotinylinsulin-avidin complexes. , 1980, The Journal of biological chemistry.

[5]  R Talhout,et al.  Thermodynamic analysis of binding of p-substituted benzamidines to trypsin. , 2001, European journal of biochemistry.

[6]  A Dean Sherry,et al.  Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. , 2006, Chemical Society reviews.

[7]  Rika Takikawa,et al.  [In-vivo visualization of gene expression using magnetic resonance imaging]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[8]  N. Green,et al.  AVIDIN. 1. THE USE OF (14-C)BIOTIN FOR KINETIC STUDIES AND FOR ASSAY. , 1963, The Biochemical journal.

[9]  Nobuhisa Iwata,et al.  19F and 1H MRI detection of amyloid β plaques in vivo , 2005, Nature Neuroscience.

[10]  Ralph Weissleder,et al.  Emerging concepts in molecular MRI. , 2007, Current opinion in biotechnology.

[11]  C. Supuran,et al.  Carbonic anhydrase inhibitors. Design of anticonvulsant sulfonamides incorporating indane moieties. , 2004, Bioorganic & medicinal chemistry letters.

[12]  J. Falke,et al.  Use of 19F NMR to probe protein structure and conformational changes. , 1996, Annual review of biophysics and biomolecular structure.

[13]  R. Mason,et al.  Synthesis and evaluation of novel enhanced gene reporter molecules: Detection of β-galactosidase activity using 19F NMR of trifluoromethylated aryl β-d-galactopyranosides , 2006 .

[14]  이재현.  Chemical design of nanoparticle probes for high-performance magnetic resonance imaging , 2008 .

[15]  Ralph Weissleder,et al.  Magnetic relaxation switches capable of sensing molecular interactions , 2002, Nature Biotechnology.

[16]  Reinskje Talhout,et al.  Understanding binding affinity: a combined isothermal titration calorimetry/molecular dynamics study of the binding of a series of hydrophobically modified benzamidinium chloride inhibitors to trypsin. , 2003, Journal of the American Chemical Society.

[17]  A. Burgen,et al.  Kinetics of complex formation between human carbonic anhydrases and aromatic sulfonamides. , 1970, Biochemistry.

[18]  C. Supuran,et al.  Carbonic anhydrase inhibitors. Design of selective, membrane-impermeant inhibitors targeting the human tumor-associated isozyme IX. , 2004, Journal of medicinal chemistry.

[19]  C. Supuran,et al.  Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. , 2003, Bioorganic & medicinal chemistry letters.

[20]  U. Dürr,et al.  Solid state 19F NMR parameters of fluorine-labeled amino acids. Part II: aliphatic substituents. , 2008, Journal of magnetic resonance.

[21]  S. Thayumanavan,et al.  Disassembly of noncovalent amphiphilic polymers with proteins and utility in pattern sensing. , 2008, Journal of the American Chemical Society.

[22]  Markus Wälchli,et al.  Paramagnetic relaxation-based 19f MRI probe to detect protease activity. , 2008, Journal of the American Chemical Society.