Synthesis and anti-metastasis activities of norcantharidin-conjugated carboxymethyl chitosan as a novel drug delivery system

Carboxymethyl chitosan (CMCS), a water-soluble derivative of chitosan possessing numerous enhanced physicochemical and biological properties, has emerged as a promising biopolymer carrier for new drug delivery. Norcantharidin (NCTD) is an effective anti-tumor compound with severe nephrotoxicity. In this study, norcantharidin-conjugated carboxymethyl chitosan (CMCS-NCTD) was synthesized to reduce systemic toxicity and improve anti-tumor efficiency of NCTD. Our results demonstrated that CMCS-NCTD could significantly inhibit migration of tumor cells both in vitro and in vivo in a dose-dependent manner (P < 0.05). The enhanced anti-tumor effects of CMCS-NCTD were confirmed by inhibiting the growth of solid tumors and extending survival time of tumor-bearing mice. Further investigation for the underlying mechanisms indicated that CMCS-NCTD could inhibit tumor angiogenesis and reduce degradation of extracellular matrix by regulating the expressions of VEGF, MMP-9 and TIMP-1. Overall, our findings suggested that CMCS-NCTD was an excellent polymer derivative for cancer treatment, and CMCS was a promising platform for efficient delivery of anti-cancer drugs.