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Nat Chem. 2014 Jun;6(6):519-26. doi: 10.1038/nchem.1920. Epub 2014 Apr 28.

Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo.

Author information

1
1] Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA [2].
2
Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA.
3
Departments of Medicine and Pathology, Division of Oncology, School of Medicine Stanford University, Stanford, California, 94305-5151, USA.

Abstract

Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.

PMID:
24848238
PMCID:
PMC4031611
DOI:
10.1038/nchem.1920
[Indexed for MEDLINE]
Free PMC Article

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