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2016 ; 15
(1
): 33
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Detection of cancer cells using SapC-DOPS nanovesicles
#MMPMID27160923
Davis HW
; Hussain N
; Qi X
Mol Cancer
2016[May]; 15
(1
): 33
PMID27160923
show ga
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.