Self-assembled gold nanoparticle molecular probes for detecting proteolytic activity in vivo.
Target-activatable fluorogenic probes based on gold nanoparticles (AuNPs) functionalized with self-assembled heterogeneous monolayers of dye-labeled peptides and poly(ethylene glycol) have been developed to visualize proteolytic activity in vivo. A one-step synthesis strategy that allows simple generation of surface-defined AuNP probe libraries is presented as a means of tailoring and evaluating probe characteristics for maximal fluorescence enhancement after protease activation. Optimal AuNP probes targeted to trypsin and urokinase-type plasminogen activator required the incorporation of a dark quencher to achieve 5- to 8-fold signal amplification. These probes exhibited extended circulation time in vivo and high image contrast in a mouse tumor model.
Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
C Jenny
CJ
Mu
David A
DA
Lavan
Robert S
RS
Langer
Bruce R
BR
Zetter
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D057075:Enzyme Assays / Q000379:methods*; D006046:Gold / Q000097:blood / Q000737:chemistry*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008854:Microscopy, Electron; D057054:Molecular Imaging; D015335:Molecular Probes / Q000097:blood / Q000737:chemistry*; D009369:Neoplasms / Q000097:blood / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry
D015335:Molecular Probes; D010455:Peptides; D011092:Polyethylene Glycols; D006046:Gold; D010447:Peptide Hydrolases