Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism.

Chitosan nanoparticles (CNP) have demonstrated anticancer activity in vitro and in vivo by a few recent researches. However, the mechanisms involved in their potential anticancer activity remain to be elucidated. In this study, the effects of CNP on tumor growth were investigated using a model of nude mice xenografted with human hepatocellular carcinoma (HCC) (BEL-7402) cells. The results demonstrated that the treatment of these nude mice with CNP significantly inhibited tumor growth and induced tumor necrosis. Furthermore, microvessel density (MVD) determination by counting immunohistologically stained tumor microvessels suggested that CNP dose-dependent tumor suppression was correlated with the inhibition of tumor angiogenesis. Mechanistically, immunohistochemical and quantitative real-time reverse transcription-polymerase reaction assays provided evidence that CNP-mediated inhibition of tumor angiogenesis was linked to impaired levels of vascular endothelial growth factor receptor 2 (VEGFR2). Due to their low or non-toxicity, CNP and their derivatives may represent a novel class of anti-cancer drug.