Objective
Cysteine proteases play pivotal roles in normal and disease processes. Alteration in cysteine protease expression and activity-pattern are the cause of various human pathologies. Several different cancers types over express members of the cysteine cathepsin proteases family. Previously we have designed and developed “smart” quenched Activity Based Probes (qABPs), that enable real time imaging of cathepsin activity in intact cells. These “smart” probes are fluorescently quenched until binding to an active protease, which causes them to become fluorescent. We have modified these qABPs enabling non-invasive imaging of cathepsin activity in cancer modules in living animals. I propose to generate novel type of ABPs that will target the cathepsin activity in tumors and will have combined imaging and therapeutic capabilities by using photodynamic therapy (PDT) strategies. Theses probes (called Photo Dynamic Activity Based Probes, PD-ABP) will allow concomitant non-invasive cancer detection and targeted treatment. Unlike traditional PDT, these probes would specifically target cancer cells, and the internal quencher would result in overall low light-induced toxicity from unbound probe. Moreover, these probes can be used for real-time tumor imaging prior to light activation, in order to better localize the subsequent photodynamic anti-cancer treatment. In this proposal we will design and synthesize PD-ABPs, we will study their biochemistry in-vitro and in cells and we will use the best PD-ABPs to image and cure cancer in small animals.
Fields of science
Call for proposal
FP7-PEOPLE-2009-RG
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Funding Scheme
MC-IRG - International Re-integration Grants (IRG)Coordinator
91904 Jerusalem
Israel