Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.
BACKGROUND
The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors.


METHODS
The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method.


CONCLUSIONS
Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis.


CONCLUSIONS
These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others.
The Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel. saritcohen84@gmail.com
Sarit
S
Cohen
Shlomo
S
Margel
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007419:Intestinal Secretions; D008422:Materials Testing; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D019887:Peanut Agglutinin / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes; D006023:Glycoproteins; D019887:Peanut Agglutinin; D012709:Serum Albumin; C047052:tumor-associated antigen 72