Abstract
Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and it has been widely used to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employed an optimized first-order bioorthogonal cyclization reaction to control self-assembly of a fluorescent small molecule, and demonstrated its in vivo applicability by imaging of casapae-3/7 activity in human tumor xenograft mouse models of chemotherapy. The in situ assembled fluorescent nanoparticles have been successfully imaged in both apoptotic cells and tumor 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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