title: Detection of cancer cells using SapC-DOPS nanovesicles.
abstract: Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for treatment. In addition, there is important evidence suggesting that SapC-DOPS may also prove to be an effective novel cancer therapeutic reagent. Given that SapC-DOPS is easily labeled with lipophilic dyes, it has been combined with the far-red fluorescent dye, CellVue Maroon (CVM), for tumor targeting studies. We also have used contrast agents incorporated in the SapC-DOPS nanovesicles for computed tomography and magnetic resonance imaging, and review that data here. Administered intravenously, the fluorescently labeled SapC-DOPS traversed the blood-brain tumor barrier enabling identification of brain tumors. SapC-DOPS-CVM also detected a variety of other mouse tumors in vivo, rendering them observable by optical imaging using IVIS and multi-angle rotational optical imaging. Dye is detected within 30 min and remains within tumor for at least 7 days, whereas non-tumor tissues were unstained (some dye observed in the liver was transient, likely representing degradation products). Additionally, labeled SapC-DOPS ex vivo delineated tumors in human histological specimens. SapC-DOPS can also be labeled with contrast reagents for computed tomography or magnetic resonance imaging. In conclusion, labeled SapC-DOPS provides a convenient, specific, and nontoxic method for detecting tumors while concurrently offering a therapeutic benefit.
authors.affiliation: Division of Hematology/Oncology, Translational Medicine Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, and Brain Tumor Center at UC Neuroscience Institute, 3512 Eden Avenue, Cincinnati, OH, 45267-0508, USA.
authors.forename: Harold W
authors.initials: HW
authors.lastname: Davis
authors.affiliation: Division of Hematology/Oncology, Translational Medicine Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, and Brain Tumor Center at UC Neuroscience Institute, 3512 Eden Avenue, Cincinnati, OH, 45267-0508, USA.
authors.forename: Nida
authors.initials: N
authors.lastname: Hussain
authors.affiliation: Division of Hematology/Oncology, Translational Medicine Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, and Brain Tumor Center at UC Neuroscience Institute, 3512 Eden Avenue, Cincinnati, OH, 45267-0508, USA. xiaoyang.qi@uc.edu.|Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. xiaoyang.qi@uc.edu.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Qi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003287:Contrast Media; D005456:Fluorescent Dyes; D006801:Humans; D023421:Models, Animal; D057054:Molecular Imaging / Q000379:methods; D064847:Multimodal Imaging / Q000379:methods; D053758:Nanoparticles; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D049231:Saposins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D010718:Phosphatidylserines; D049231:Saposins; C042511:1,2-dioleoylphosphatidylserine
keywords: Cancer; Contrast agents; Phosphatidylserine; SapC-DOPS; Saposin C; Tumor imaging