Journal
NATURE CHEMISTRY
Volume 6, Issue 6, Pages 519-526Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.1920
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Funding
- Stanford University National Cancer Institute (NCI) Centers of Cancer Nanotechnology Excellence [1U54CA151459-01]
- NCI ICMIC@Stanford [1P50CA114747-06]
- Institutional Development Award from the Department of Defense Breast Cancer Research Program [W81XWH 09 1 0057]
- Susan Komen Breast Cancer Foundation
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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.
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