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Sci Rep. 2017 Jan 25;7:40989. doi: 10.1038/srep40989.

Novel approach for the detection of intraperitoneal micrometastasis using an ovarian cancer mouse model.

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Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Pharmaceutical Sciences, Texas A&M HSC, College Station, TX, USA.
Department of Pathology, Yale University School of Medicine, New Haven CT, USA.


Patients with epithelial ovarian cancer have the best overall survival when maximal surgical effort is accomplished. However, despite numerous technological advances, surgery still relies primarily on white-light reflectance and the surgeon's vision. As such, micrometastases are usually missed and most patients clinically classified as a complete responder eventually recur and succumb to the disease. Our objective is to develop optical enhancers which can aid in the visualization of ovarian cancer micrometastasis. To this end we developed a nanoparticle (NP) platform, which is specifically targeted to the tumor microenvironment. Targeting is achieved by coating FDA-approved PLGA-PEG NP with the peptide sequence RGD, which binds with high affinity to αVβ3 integrins present in both the tumor-associated neovasculature and on the surface of ovarian cancer cells. Administration of the NP platform carrying fluorescent dyes to mice bearing intraperitoneal ovarian cancer allowed visualization of tumor-associated vasculature and its contrast against normal blood vessels. More importantly, we demonstrate the visualization of intraperitoneal ovarian cancer micrometastasis as small as 100 μm with optimal resolution. Finally, we demonstrate that the fluorescent dye cargo was able to penetrate intra-tumorally. Such modality could be used to allow microscopic surgical debulking to assure maximal surgical effort.

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