Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo.
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.
1] Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA [2].
Deju
D
Ye
1] Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA [2].
Adam J
0000000169525217
AJ
Shuhendler
Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA.
Lina
L
Cui
Departments of Medicine and Pathology, Division of Oncology, School of Medicine Stanford University, Stanford, California, 94305-5151, USA.
Ling
L
Tong
Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA.
Sui Seng
SS
Tee
Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA.
Grigory
G
Tikhomirov
Departments of Medicine and Pathology, Division of Oncology, School of Medicine Stanford University, Stanford, California, 94305-5151, USA.
Dean W
DW
Felsher
Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, Stanford, California 94305-5484, USA.
Jianghong
J
Rao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D003500:Cyclization; D004318:Doxycycline / Q000494:pharmacology; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D005456:Fluorescent Dyes; D020169:Caspases; D004318:Doxycycline