The metastatic stage-dependent mucosal expression of sialic acid is a potential marker for targeting colon cancer with cationic polymers.
OBJECTIVE
Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was to elucidate whether the overexpression of sialic acid (SA) on colonic malignant tissues could be utilized for drug targeting by cationic polymers.


METHODS
Cell lines (IEC-6, SW-480 and SW-620) and colon polyps and normal adjacent tissues harvested from dimethylhydrazine (DMH) induced rats were used as in vitro and in vivo models of different metastatic stages of colon cancer. SA expression was identified by fluorescent wheat germ agglutinin (WGA), and verified by pretreatment with neuraminidase. The role of mucus in the mucosal binding experiments was explored by pretreatment with dithiothreitol (DTT). The binding of FITC labeled cationic polymers of various degrees of cationization to normal and malignant colonic cells and tissue was measured.


RESULTS
SA was overexpressed on malignant colonic cells and tissues, and its expression correlated to the metastatic stage in vitro. The binding of the cationic copolymers to the cell lines and tissues correlated with the charge density of the polymer and with the metastatic stage of the cell line. The interaction between the malignant colonic cells and tissues with the polymers was SA dependent and increased after mucus removal.


CONCLUSIONS
Cationic polymers could be used as a targeting tool to colonic malignant epithelium, to be implemented in drug delivery and diagnosis.
Azab
Abdel Kareem
AK
Faculty of Medicine, School of Pharmacy, Department of Pharmaceutics, The Hebrew University of Jerusalem, Jerusalem, Israel.
Kleinstern
Jackie
J
Srebnik
Morris
M
Rubinstein
Abraham
A
D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051381:Rats; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D000178:Acrylamides; D014909:Wheat Germ Agglutinins; D019158:N-Acetylneuraminic Acid