Specific detection of integrin αvβ3 by light-up bioprobe with aggregation-induced emission characteristics.

Specific bioprobes with fluorescence turn-on response are highly desirable for high contrast biosensing and imaging. In this work, we developed a new generation bioprobe by integrating tetraphenylsilole, a fluorogenic unit with aggregation-induced emission (AIE) characteristic, with cyclic arginine-glycine-aspartic acid tripeptide (cRGD), a targeting ligand to integrin α(v)β(3) receptor. Emission of the AIE probe is switched on upon its specific binding to integrin α(v)β(3), which allows quantitative detection of integrin α(v)β(3) in solution and real-time imaging of the binding process between cRGD and integrin α(v)β(3) on cell membrane. The probe can be used for tracking integrin α(v)β(3) and for identifying integrin α(v)β(3)-positive cancer cells.

[1]  Yongqiang Dong,et al.  Fluorescent "light-up" bioprobes based on tetraphenylethylene derivatives with aggregation-induced emission characteristics. , 2006, Chemical communications.

[2]  Ben Zhong Tang,et al.  Aggregation-induced Emission of Silole Molecules and Polymers: Fundamental and Applications , 2009 .

[3]  Shuang Liu.  Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. , 2009, Bioconjugate chemistry.

[4]  B. Felding-Habermann,et al.  Integrin adhesion receptors in tumor metastasis , 2004, Clinical & Experimental Metastasis.

[5]  Morten Meldal,et al.  Cu-catalyzed azide-alkyne cycloaddition. , 2008, Chemical reviews.

[6]  Ben Zhong Tang,et al.  Biocompatible Nanoparticles with Aggregation‐Induced Emission Characteristics as Far‐Red/Near‐Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications , 2012 .

[7]  Daniel‐Adriano Silva,et al.  Monitoring and inhibition of insulin fibrillation by a small organic fluorogen with aggregation-induced emission characteristics. , 2012, Journal of the American Chemical Society.

[8]  R. Moats,et al.  In vivo Near-Infrared Fluorescence Imaging of Integrin αvβ3 in Brain Tumor Xenografts , 2004, Cancer Research.

[9]  R. Khokha,et al.  Molecular mechanisms of tumor invasion and metastasis: an integrated view. , 2003, Current molecular medicine.

[10]  Michael S. Pepper,et al.  αvβ3 and αvβ5 integrin antagonists inhibit angiogenesis in vitro , 2004, Angiogenesis.

[11]  J. B. Birks,et al.  Photophysics of aromatic molecules , 1970 .

[12]  Manfred Schwab,et al.  Arginine-glycine-aspartic acid (RGD)-peptide binds to both tumor and tumor-endothelial cells in vivo. , 2002, Cancer research.

[13]  Ben Zhong Tang,et al.  Aggregation-induced emission: phenomenon, mechanism and applications. , 2009, Chemical communications.

[14]  T. Koyama,et al.  Fluorescence quenching detection of peanut agglutinin based on photoluminescent silole-core carbosilane dendrimer peripherally functionalized with lactose , 2009 .

[15]  Deqing Zhang,et al.  The convenient fluorescence turn-on detection of heparin with a silole derivative featuring an ammonium group. , 2008, Chemical communications.

[16]  H. Kolb,et al.  The growing impact of click chemistry on drug discovery. , 2003, Drug discovery today.

[17]  Ben Zhong Tang,et al.  Acetylenic polymers: syntheses, structures, and functions. , 2009, Chemical reviews.

[18]  Yujian He,et al.  Tetraphenylethylene-based glycoconjugate as a fluorescence "turn-on" sensor for cholera toxin. , 2011, Chemistry, an Asian journal.

[19]  Ka Ming Ng,et al.  Cytophilic Fluorescent Bioprobes for Long‐Term Cell Tracking , 2011, Advanced materials.

[20]  E Biganzoli,et al.  Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[21]  Yongqiang Dong,et al.  Endowing hexaphenylsilole with chemical sensory and biological probing properties by attaching amino pendants to the silolyl core , 2007 .

[22]  P. Low,et al.  Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results , 2011, Nature Medicine.

[23]  Masato Tanaka,et al.  A displacement assay for the sensing of protein interactions using sugar–tetraphenylethene conjugates , 2010 .

[24]  P. Choyke,et al.  New strategies for fluorescent probe design in medical diagnostic imaging. , 2010, Chemical reviews.

[25]  Masato Tanaka,et al.  Fluorescence turn-on sensing of lectins with mannose-substituted tetraphenylethenes based on aggregation-induced emission. , 2010, Chemistry, an Asian journal.

[26]  A. Reynolds,et al.  Integrins in angiogenesis: multitalented molecules in a balancing act , 2003, Cell and Tissue Research.

[27]  H S Kwok,et al.  Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. , 2001, Chemical communications.

[28]  Ben Zhong Tang,et al.  Synthesis, Light Emission, Nanoaggregation, and Restricted Intramolecular Rotation of 1,1-Substituted 2,3,4,5-Tetraphenylsiloles , 2003 .

[29]  M. Roberts,et al.  PDGF-regulated rab4-dependent recycling of αvβ3 integrin from early endosomes is necessary for cell adhesion and spreading , 2001, Current Biology.

[30]  A. Taherian,et al.  Differences in integrin expression and signaling within human breast cancer cells , 2011, BMC Cancer.

[31]  Ben Zhong Tang,et al.  Fluorescent bio/chemosensors based on silole and tetraphenylethene luminogens with aggregation-induced emission feature , 2010 .

[32]  Ben Zhong Tang,et al.  Aggregation-induced emission. , 2011, Chemical Society reviews.

[33]  Vasilis Ntziachristos,et al.  Enhancing Surgical Vision by Using Real-Time Imaging of αvβ3-Integrin Targeted Near-Infrared Fluorescent Agent , 2011, Annals of Surgical Oncology.