Abstract：
:The possibility of measuring binding of small-molecule drugs to desired targets in live cells could provide a better understanding of drug action. However, current approaches mostly yield static data, require lysis or rely on indirect assays and thus often provide an incomplete understanding of drug action. Here, we present a multiphoton fluorescence anisotropy microscopy live cell imaging technique to measure and map drug-target interaction in real time at subcellular resolution. This approach is generally applicable using any fluorescently labelled drug and enables high-resolution spatial and temporal mapping of bound and unbound drug distribution. To illustrate our approach we measure intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP-ribose) polymerase inhibitor, in live cells and within a tumour in vivo. These results are the first generalizable approach to directly measure drug-target binding in vivo and present a promising tool to enhance understanding of drug activity.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Dubach JM,Vinegoni C,Mazitschek R,Fumene Feruglio P,Cameron LA,Weissleder Rdoi
10.1038/ncomms4946subject
Has Abstractpub_date
2014-05-28 00:00:00pages
3946issn
2041-1723pii
ncomms4946journal_volume
5pub_type
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