Fluorescent light-up probe with aggregation-induced emission characteristics for in vivo imaging of cell apoptosis.

In this paper, a new live-cell permeable, fluorescent light-up probe comprised of a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic tetraphenylethene pyridinium unit has been developed for in vivo cell apoptosis imaging and drug screening. The probe shows a specific light-up response to activated caspase-3/7 with a high signal-to-background ratio. The significant fluorescence turn-on response of the probe is due to the aggregation of cleaved hydrophobic residues that populate the radiative decay channels. With good water solubility and biocompatibility, the probe is demonstrated to be a promising candidate for in vivo real time monitoring of caspase activation and in situ screening of apoptosis-inducing drugs.

[1]  B. Liu,et al.  Lipid-PEG-folate encapsulated nanoparticles with aggregation induced emission characteristics: cellular uptake mechanism and two-photon fluorescence imaging. , 2012, Small.

[2]  L. de Ridder,et al.  Phosphatidylserine exposure during early primary necrosis (oncosis) in JB6 cells as evidenced by immunogold labeling technique , 2004, Apoptosis.

[3]  D. Ding,et al.  Aggregation-induced red-NIR emission organic nanoparticles as effective and photostable fluorescent probes for bioimaging , 2012 .

[4]  Yigong Shi,et al.  A structural view of mitochondria-mediated apoptosis , 2001, Nature Structural Biology.

[5]  R. Herrmann,et al.  Screening for Compounds That Induce Apoptosis of Cancer Cells Grown as Multicellular Spheroids , 2008, Journal of biomolecular screening.

[6]  Kai Yang,et al.  In Vivo Study of the Effects of Peptide-Conjugated Near-Infrared Fluorescent Quantum Dots on the Tumorigenic and Lymphatic Metastatic Capacities of Squamous Cell Carcinoma Cell Line Tca8113 and U14 , 2010, International journal of molecular sciences.

[7]  Z. Darżynkiewicz,et al.  Detection of caspases activation by fluorochrome-labeled inhibitors: Multiparameter analysis by laser scanning cytometry. , 2001, Cytometry.

[8]  Ben Zhong Tang,et al.  Real-time monitoring of cell apoptosis and drug screening using fluorescent light-up probe with aggregation-induced emission characteristics. , 2012, Journal of the American Chemical Society.

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

[10]  Deqing Zhang,et al.  Convenient and continuous fluorometric assay method for acetylcholinesterase and inhibitor screening based on the aggregation-induced emission. , 2009, Analytical chemistry.

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

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

[13]  J. Ripoll,et al.  Visualization of antitumor treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Mach,et al.  Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis. , 2006, Bioorganic & medicinal chemistry letters.

[15]  Kwangmeyung Kim,et al.  Real time, high resolution video imaging of apoptosis in single cells with a polymeric nanoprobe. , 2011, Bioconjugate chemistry.

[16]  Alexei Degterev,et al.  A decade of caspases , 2003, Oncogene.

[17]  Vasilis Ntziachristos,et al.  Shedding light onto live molecular targets , 2003, Nature Medicine.

[18]  B. Tang,et al.  BSA-tetraphenylethene derivative conjugates with aggregation-induced emission properties: fluorescent probes for label-free and homogeneous detection of protease and α1-antitrypsin. , 2011, The Analyst.

[19]  Z. Darżynkiewicz,et al.  Activation of caspases measured in situ by binding of fluorochrome-labeled inhibitors of caspases (FLICA): correlation with DNA fragmentation. , 2000, Experimental cell research.

[20]  Matthew Bogyo,et al.  Noninvasive optical imaging of apoptosis by caspase-targeted activity-based probes , 2009, Nature Medicine.

[21]  Hoi Sing Kwok,et al.  Construction of efficient solid emitters with conventional and AIE luminogens for blue organic light-emitting diodes , 2011 .

[22]  R. Weissleder,et al.  Near-infrared fluorescent imaging of tumor apoptosis. , 2003, Cancer research.

[23]  S. Korsmeyer,et al.  Cell Death in Development , 1999, Cell.

[24]  Roland Hustinx,et al.  Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  Vasilis Ntziachristos,et al.  Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy. , 2003, Neoplasia.

[26]  Xiaoyuan Chen,et al.  Apoptosis Imaging: Beyond Annexin V , 2010, The Journal of Nuclear Medicine.

[27]  Tak W. Mak,et al.  Pathways of apoptotic and non-apoptotic death in tumour cells , 2004, Nature Reviews Cancer.

[28]  Ben Zhong Tang,et al.  Specific detection of integrin αvβ3 by light-up bioprobe with aggregation-induced emission characteristics. , 2012, Journal of the American Chemical Society.

[29]  Kai Li,et al.  Photostable fluorescent organic dots with aggregation-induced emission (AIE dots) for noninvasive long-term cell tracing , 2013, Scientific Reports.

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

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

[32]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[33]  Thomas L. Chenevert,et al.  Noninvasive real-time imaging of apoptosis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Yigong Shi,et al.  Molecular mechanisms of caspase regulation during apoptosis , 2004, Nature Reviews Molecular Cell Biology.

[35]  M. Grütter,et al.  Caspases: key players in programmed cell death. , 2000, Current opinion in structural biology.

[36]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[37]  Deqing Zhang,et al.  Continuous on-site label-free ATP fluorometric assay based on aggregation-induced emission of silole. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[38]  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 .