NIR-II Aza-BODIPY Dyes Bioconjugated to Monoclonal Antibody Trastuzumab for Selective Imaging of HER2-Positive Ovarian Cancer
Résumé
Using fluorescence guided surgery (FGS) to cytoreductive surgery helps achieving complete resection of microscopic ovarian tumors. The use of visible and NIR-I fluorophores has led to beneficial results in clinical trials; however, involving NIR-II dyes seems to outperform those benefits due to the deeper tissue imaging and higher signal/noise ratio attained within the NIR-II optical window. In this context, we developed NIR-II emitting dyes targeting HER2-positive ovarian tumors, by coupling water-soluble NIR-II aza-BODIPY dyes to the FDA approved anti-HER2 antibody, namely trastuzumab. These bioconjugated NIR-II-emitting dyes displayed a prolonged stability in serum, and a maintained affinity towards HER2 in vitro. We obtained selective targeting of HER2 positive tumors (SKOV-3) in vivo, with a favorable tumor accumulation. We demonstrated the fluorescence properties and the specific HER2 binding of the bioconjugated dyes in vivo, and thus their potential for NIR-II FGS in the cancer setting.
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