- Cover a wide range of cancers, such as colorectal (80% CA19-9 positive), pancreatic (80% positive), biliary tract (70-80% positive), gastric (20-50% positive)
- Prevents a hepatotoxicity through the parallel treatment of mannose
- Applicable for in vivo imaging of CA19-9 positive tumor by use of delivery system
Background and Technology
Fucosylated antigens like CA19-9 or SLX, serve as markers for cancer detection and evaluation of anti-tumor effects. Overexpression of fucosyltransferase(FUTs) in pancreatic cancer has been reported and known to accelerate malignant transformation.
The inventors found the novel mechanism that CA19-9 positive cells uptake L-Fucose through a specific receptor. So, they developed fucose-bound liposome as vehicles for delivery of anti-cancer drugs specifically to cancer cells.
In addition, parallel administration of mannose showed that the efficacy of this drug delivery increased and relieved the hepatotoxicity by blocking undesired binding to lectin expressed on liver tissue.
Data and Figure
- An example of Liposome preparation scheme showing sugar chains. HSA: human serum albumin, BS3: bis(sulfosuccinimidyl) suberate, Tris: (hydroxymehyl) aminomhane, DTSSP: 3,3-dithiobis (sulfosuccinimidylpropionate); Left figure
- Fucose-liposome-cisplatin showed fucose-dependent cytotoxicity in pancreatic cancer cells.
- v. administration of fucose-liposome-cisplatin (2mg/kg) suppressed tumor growth and prolonged survival of xenograft pancreatic cancer model mice with no side effect.; Right Figure
- Parallel administration of D-mannose increased the distribution of fucose-liposome to CA19-9 positive tumor in xenograft mice
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