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Abstract #3163

Harnessing Competing Endocytic Pathways for Overcoming the Tumor-Blood Barrier: MRI and NIR Imaging of Bifunctional Contrast Media

Helena Migalovich-Sheikhet1, Vyacheslav Kalchenko2, Nava Nevo2, Fortune Kohen1, Michal Neeman1

1Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; 2Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel

The uptake of targeted bifunctional daidzein-BSA MRI/NIR contrast media to human ovarian carcinoma cells was achieved by two competing endocytic pathways. One is BSA mediated-caveolae dependent and could be modulated by nystatin or BSA saturation, and the second is daidzein mediated and caveolae independent. The ability to manipulate caveolae-mediated sequestration of albumin by perivascular tumor myofibroblasts allowed to effectively overcome the tumor-blood barrier, increasing delivery of daidzein-BSA-GdDTPA/CyTE777 to the tumor cells. In view of the cardinal role of albumin in affecting the bioavailability of drugs, this approach could potentially facilitate the delivery of therapeutics and contrast media to the tumor.