title: Lectin-mediated cytotoxicity and specificity of 5-fluorouracil conjugated with peanut agglutinin (5-Fu-PNA) in vitro.
abstract: In order to take advantage of the biorecognition between lectin and carbohydrate for targeted drug delivery, the lectin of peanut (Arachis hypogaea) agglutinin (PNA) was coupled by fixing its amino groups to the carbodiimide-activated carboxylic groups of 5-fluorouracil (5-Fu) derivative (N1-substituted 5-Fu acetate) to form 5-Fu-PNA conjugate. When the coupling reaction was carried out in the presence of d-galactose (d-gal, specific sugar for PNA), the affinity of PNA was maintained after its coupling to N1-substituted 5-Fu acetate, which was confirmed by the result of the haemagglutination test. Otherwise, PNA would lose its affinity after the cross-linking reaction. The cytotoxicity, specificity and selectivity of 5-Fu-PNA were examined on the human colorectal cancer cell line LoVo and the human normal liver cell line Chang using MTT assay. Compared with free drug, the active conjugate, which maintained the affinity of lectin, had similar cytotoxic effect on LoVo cells with much lower cytotoxicity on Chang cells On the other hand, lower cytotoxic effects on LoVo cells were observed for the non-active conjugate even at higher drug concentrations. The cytotoxic effect of conjugate was specific because only the active conjugate could inhibit the growth of LoVo cells in a dose- and time-dependent manner as that of the free drug. The achieved results indicate the significance to maintain the affinity of lectin for lectin-mediated cytotoxicity. Still, the potential of 5-Fu-PNA conjugate as a targeting agent for colorectal cancer needs to be further investigated in vivo.
authors.affiliation: Key laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Cai
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006386:Hemagglutination Tests; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D019887:Peanut Agglutinin / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D019887:Peanut Agglutinin; D005472:Fluorouracil