Bioorthogonal Supramolecular Latching Inside Live Animals and Its Application for In Vivo Cancer Imaging.

Here we demonstrate a supramolecular latching tool for bioorthogonal noncovalent anchoring of small synthetic molecules in live animal models using a fully synthetic high-affinity binding pair between cucurbit[7]uril (CB[7]) and adamantylammonium (AdA). This supramolecular latching system is small (~1 kDa), ensuring efficient uptake into cells, tissues, and whole organisms. It is also chemically robust and resistant to enzymatic degradation, and analogous to well-characterized biological systems in terms of noncovalent binding. Occurrence of fluorescence resonance energy transfer (FRET) between cyanine 3-CB[7] (Cy3-CB[7]) and boron-dipyrromethene-AdA (BDP-AdA) inside a live worm (Caenorhabditis elegans) indicates efficient in situ high-affinity association between AdA and CB[7] inside live animals. In addition, selective visualization of a cancer site of a live mouse upon supramolecular latching of cyanine 5-AdA (Cy5-AdA) on prelocalized CB[7]-conjugating antibody on the cancer site demonstrates the potential of this synthetic system for in vivo cancer imaging. These findings provide a fresh insight into the development of new chemical biology tools and medical therapeutic systems.

[1]  Ara Lee,et al.  Cucurbit[7]uril-conjugated dyes as live cell imaging probes: investigation on their cellular uptake and excretion pathways. , 2019, Organic & biomolecular chemistry.

[2]  M. Webber,et al.  Spatially Defined Drug Targeting by in Situ Host–Guest Chemistry in a Living Animal , 2019, ACS central science.

[3]  L. Isaacs,et al.  Adamantane/Cucurbituril: A Potential Pretargeted Imaging Strategy in Immuno-PET , 2018, Molecular imaging.

[4]  Sarit S. Agasti,et al.  Synthetic Host–Guest Assembly in Cells and Tissues: Fast, Stable, and Selective Bioorthogonal Imaging via Molecular Recognition , 2018, Analytical chemistry.

[5]  Robert Langer,et al.  Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts. , 2018, Chemical reviews.

[6]  G. Canavese,et al.  Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer , 2018, Chemical engineering journal.

[7]  Ara Lee,et al.  Supramolecular latching system based on ultrastable synthetic binding pairs as versatile tools for protein imaging , 2018, Nature Communications.

[8]  Meng Li,et al.  Autophagy Caught in the Act: A Supramolecular FRET Pair Based on an Ultrastable Synthetic Host-Guest Complex Visualizes Autophagosome-Lysosome Fusion. , 2018, Angewandte Chemie.

[9]  Anselm F. L. Schneider,et al.  Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells. , 2017, Nature chemistry.

[10]  Kimoon Kim,et al.  Ultrastable Artificial Binding Pairs as a Supramolecular Latching System: A Next Generation Chemical Tool for Proteomics. , 2017, Accounts of chemical research.

[11]  Kimoon Kim,et al.  Can we beat the biotin-avidin pair?: cucurbit[7]uril-based ultrahigh affinity host-guest complexes and their applications. , 2015, Chemical Society reviews.

[12]  Oren A Scherman,et al.  Cucurbituril-Based Molecular Recognition. , 2015, Chemical reviews.

[13]  P. Drake,et al.  An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety. , 2015, Current opinion in chemical biology.

[14]  Sadik Esener,et al.  Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans , 2015, Nature Communications.

[15]  S. Yao,et al.  Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s. , 2015, Journal of the American Chemical Society.

[16]  Yanli Zhao,et al.  Biomedical Applications of Supramolecular Systems Based on Host-Guest Interactions. , 2015, Chemical reviews.

[17]  W. Nau,et al.  Cucurbiturils: from synthesis to high-affinity binding and catalysis. , 2015, Chemical Society reviews.

[18]  Mitsuru Hashida,et al.  Ultrasound induced cancer immunotherapy. , 2014, Advanced drug delivery reviews.

[19]  Lyle Isaacs,et al.  Stimuli Responsive Systems Constructed Using Cucurbit[n]uril-Type Molecular Containers , 2014, Accounts of chemical research.

[20]  Y. Liu,et al.  Supra-amphiphilic aggregates formed by p-sulfonatocalix[4]arenes and the antipsychotic drug chlorpromazine. , 2013, Soft matter.

[21]  S. Schuster,et al.  Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. , 2013, Nature chemical biology.

[22]  Jianxiang Zhang,et al.  Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective. , 2013, Advanced drug delivery reviews.

[23]  Yi Pan,et al.  pH-responsive supramolecular vesicles based on water-soluble pillar[6]arene and ferrocene derivative for drug delivery. , 2013, Journal of the American Chemical Society.

[24]  Jennifer H Elisseeff,et al.  Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation , 2013, Advanced functional materials.

[25]  A. Chisholm,et al.  The Caenorhabditis elegans epidermis as a model skin. I: development, patterning, and growth , 2012, Wiley interdisciplinary reviews. Developmental biology.

[26]  Daxiang Cui,et al.  HER2 monoclonal antibody conjugated RNase-A-associated CdTe quantum dots for targeted imaging and therapy of gastric cancer. , 2012, Biomaterials.

[27]  Yong Yang,et al.  Pillararenes, a new class of macrocycles for supramolecular chemistry. , 2012, Accounts of chemical research.

[28]  J. Wolchok,et al.  Antibody therapy of cancer , 2012, Nature Reviews Cancer.

[29]  Xiaoyong Lu,et al.  Cucurbituril chemistry: a tale of supramolecular success , 2012 .

[30]  Akira Harada,et al.  Photoswitchable gel assembly based on molecular recognition , 2012, Nature Communications.

[31]  B. Dietzek,et al.  Fluorescence-based fixative and vital staining of lipid droplets in Caenorhabditis elegans reveal fat stores using microscopy and flow cytometry approaches[S] , 2011, Journal of Lipid Research.

[32]  G. Whitesides,et al.  Chemistry and the worm: Caenorhabditis elegans as a platform for integrating chemical and biological research. , 2011, Angewandte Chemie.

[33]  Jong Seung Kim,et al.  Recognition of amino acids by functionalized calixarenes. , 2011, Chemical Society reviews.

[34]  Roel Deckers,et al.  Ultrasound triggered, image guided, local drug delivery. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Christian Bailly,et al.  Strategies and challenges for the next generation of therapeutic antibodies , 2010, Nature Reviews Immunology.

[36]  W. Bou-Assaly,et al.  Cetuximab (Erbitux) , 2010, American Journal of Neuroradiology.

[37]  R. Medzhitov.  Recognition of microorganisms and activation of the immune response , 2007, Nature.

[38]  Young Ho Ko,et al.  Functionalized cucurbiturils and their applications. , 2007, Chemical Society reviews.

[39]  Heinrich Leonhardt,et al.  Targeting and tracing antigens in live cells with fluorescent nanobodies , 2006, Nature Methods.

[40]  Kam W Leong,et al.  Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO triblock copolymers and alpha-cyclodextrin for controlled drug delivery. , 2006, Biomaterials.

[41]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[42]  T. Allen.  Ligand-targeted therapeutics in anticancer therapy , 2002, Nature Reviews Cancer.

[43]  R. Ellis,et al.  Macromolecular crowding: an important but neglected aspect of the intracellular environment. , 2001, Current opinion in structural biology.

[44]  Akira Harada,et al.  Macroscopic self-assembly through molecular recognition. , 2011, Nature chemistry.

[45]  J. Ravetch,et al.  Fcγ receptors as regulators of immune responses , 2008, Nature Reviews Immunology.