A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals

We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples.

[1]  C. Maggi,et al.  The mammalian tachykinin receptors. , 1995, General pharmacology.

[2]  J. Mcclellan A GROWING FAMILY , 2002 .

[3]  C. Palma Tachykinins and their receptors in human malignancies. , 2006, Current drug targets.

[4]  Eric J. Nestler,et al.  New approaches to antidepressant drug discovery: beyond monoamines , 2006, Nature Reviews Neuroscience.

[5]  Stephen P. Hunt,et al.  Altered nociception, analgesia and aggression in mice lacking the receptor for substance P , 1998, Nature.

[6]  E.,et al.  Paramagnetic Metal Complexes as Water Proton Relaxation Agents for NMR Imaging : Theory and Design , 2001 .

[7]  Jianzhang Zhao,et al.  An enantioselective fluorescent sensor for sugar acids. , 2004, Journal of the American Chemical Society.

[8]  Cuichen Wu,et al.  A targeted, self-delivered, and photocontrolled molecular beacon for mRNA detection in living cells. , 2013, Journal of the American Chemical Society.

[9]  S. Belinsky,et al.  Gene-promoter hypermethylation as a biomarker in lung cancer , 2004, Nature Reviews Cancer.

[10]  R. Hargreaves,et al.  Clinical biomarkers in drug discovery and development , 2003, Nature Reviews Drug Discovery.

[11]  P. Sebastiani,et al.  Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer , 2007, Nature Medicine.

[12]  D. Payan,et al.  Binding characteristics and affinity labeling of protein constituents of the human IM-9 lymphoblast receptor for substance P. , 1986, The Journal of biological chemistry.

[13]  V. Almendro,et al.  Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2 , 2012, Journal of cellular physiology.

[14]  H. Tian,et al.  Photoelectric conversion properties of four novel carboxylated hemicyanine dyes on TiO2 electrode , 2003 .

[15]  S. Shaw Molecular imaging in cardiovascular disease: targets and opportunities , 2009, Nature Reviews Cardiology.

[16]  E. Unger,et al.  Status of liposomes as MR contrast agents , 1993, Journal of magnetic resonance imaging : JMRI.

[17]  Klara Stefflova,et al.  In vivo detection of phospholipase C by enzyme-activated near-infrared probes. , 2011, Bioconjugate chemistry.

[18]  Young-Tae Chang,et al.  The role of "disaggregation" in optical probe development. , 2014, Chemical Society reviews.

[19]  Silvio Aime,et al.  A quantitative relaxometric version of the ELISA test for the measurement of cell surface biomarkers. , 2014, Angewandte Chemie.

[20]  J. Laissue,et al.  Substance‐P receptors in human primary neoplasms: Tumoral and vascular localization , 1995, International journal of cancer.

[21]  Weihong Tan,et al.  Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. , 2013, Journal of the American Chemical Society.

[22]  R. Lauffer,et al.  Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design , 1987 .

[23]  T. Reineke,et al.  Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential? , 2012, Macromolecules.

[24]  Zhen Cheng,et al.  Ultrasmall near-infrared non-cadmium quantum dots for in vivo tumor imaging. , 2010, Small.

[25]  S. Fineschi,et al.  Neurokinin-1 receptor blockade and murine lung tumorigenesis. , 2006, American journal of respiratory and critical care medicine.

[26]  C. Maggi,et al.  Tachykinins and tachykinin receptors: a growing family. , 2004, Life sciences.

[27]  Andrea D Thompson,et al.  Analysis of the interaction of BCL9 with beta-catenin and development of fluorescence polarization and surface plasmon resonance binding assays for this interaction. , 2009, Biochemistry.

[28]  A. Ulman,et al.  Absorption and second-harmonic generation of monomer and aggregate hemicyanine dye in Langmuir-Blodgett films. , 1988, Optics letters.

[29]  D. Ding,et al.  Bioprobes based on AIE fluorogens. , 2013, Accounts of chemical research.

[30]  Yang Liu,et al.  Changing the Behavior of Chromophores from Aggregation‐Caused Quenching to Aggregation‐Induced Emission: Development of Highly Efficient Light Emitters in the Solid State , 2010, Advanced materials.

[31]  Weihong Tan,et al.  Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. , 2012, Analytical chemistry.

[32]  M. Muñoz,et al.  Involvement of substance P and the NK-1 receptor in cancer progression , 2013, Peptides.

[33]  Ronghua Yang,et al.  Functional DNA-Containing Nanomaterials: Cellular Applications in Biosensing, Imaging, and Targeted Therapy , 2014, Accounts of chemical research.

[34]  In vitro and in vivo magnetic resonance detection of tumor cells by targeting glutamine transporters with Gd-based probes. , 2006, Journal of medicinal chemistry.

[35]  Robert W. Bruce,et al.  Theory and design , 2012 .

[36]  C. Fowler,et al.  Substance P enhances forskolin-stimulated cyclic AMP production in human UC11MG astrocytoma cells. , 1994, Methods and findings in experimental and clinical pharmacology.

[37]  Peter Caravan,et al.  Gd(DOTAla): a single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development. , 2012, Journal of the American Chemical Society.

[38]  R. Zhuo,et al.  Multifunctional envelope-type mesoporous silica nanoparticles for tumor-triggered targeting drug delivery. , 2013, Journal of the American Chemical Society.

[39]  Weihong Tan,et al.  Engineering polymeric aptamers for selective cytotoxicity. , 2011, Journal of the American Chemical Society.

[40]  F. Esteban,et al.  Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours. , 2008, Oral oncology.

[41]  Peter Caravan,et al.  Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. , 2006, Chemical Society reviews.

[42]  Tao Yi,et al.  Peptide functionalized polydiacetylene liposomes act as a fluorescent turn-on sensor for bacterial lipopolysaccharide. , 2011, Journal of the American Chemical Society.

[43]  Brian L Hood,et al.  Lung cancer serum biomarker discovery using glycoprotein capture and liquid chromatography mass spectrometry. , 2010, Journal of proteome research.

[44]  Satyajit Mayor,et al.  Folate receptor endocytosis and trafficking. , 2004, Advanced drug delivery reviews.

[45]  Weihong Tan,et al.  Aptamers from cell-based selection for bioanalytical applications. , 2013, Chemical reviews.

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

[47]  U. Schubert,et al.  High molecular weight supramolecular polymers containing both terpyridine metal complexes and ureidopyrimidinone quadruple hydrogen-bonding units in the main chain. , 2005, Journal of the American Chemical Society.

[48]  C. Böttcher,et al.  Switchable supramolecular polymers from the self-assembly of a small monomer with two orthogonal binding interactions. , 2011, Journal of the American Chemical Society.

[49]  S. Aime,et al.  MRI visualization of melanoma cells by targeting overexpressed sialic acid with a Gd(III)-dota-en-pba imaging reporter. , 2013, Angewandte Chemie.

[50]  Ben Zhong Tang,et al.  Targeted theranostic platinum(IV) prodrug with a built-in aggregation-induced emission light-up apoptosis sensor for noninvasive early evaluation of its therapeutic responses in situ. , 2014, Journal of the American Chemical Society.

[51]  F. Hirsch,et al.  Early detection and screening of lung cancer , 2010, Expert review of molecular diagnostics.