Tumour cell uptake of lactosaminated and intact N-succinylchitosans and antitumour effects of conjugates with mitomycin C

Background: The relationship between the uptake of lactosaminated and intact N-succinyl-chitosans into hepatoma cells (MH134 and AH130) and liver metastatic tumour model cells (M5076) and the antitumour effects of their conjugates with mitomycin C (MMC) were investigated. Materials and Methods: Fluorescently-labelled carriers were administered to tumour-bearing mice. The fluorescence intensity and microscopic examinations were performed at 1 hour post-injection. The antitumour effects were examined according to several schedules: one of them was the administration of each conjugate at a dose of 4 mg eq. MMC/kg x 4 days at 3 days post-inoculation. Results: A difference in uptake was found by measurement of fluorescence intensity between both carriers only in MH134 cells, but was not recognized by fluorescence microscopy. Among these cell lines, the uptake of carriers into M5076 cells tended to be the most extensive. The difference in antitumour effects of the conjugates against MH134 and M5076 was reflected by the biodistribution study. Conclusion: The pattern of antitumour effects was markedly different among cell lines of different origins.