Primary in vitro and in vivo evaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment.

Two novel polymer-drug conjugates norcantharidin-poly(vinyl alcohol) and norcantharidin-chitosan (NCTD-PVA and NCTD-CS) were synthesized via alcoholysis reaction and characterized by (1)H-NMR and FTIR. NCTD was released from the conjugates via hydrolysis, faster in PBS (pH 5.0) than that in PBS (pH 7.4). NCTD-PVA and NCTD-CS inhibited human esophageal carcinoma ECA-109 cell and murine breast cancer EMT6 cell growth in a dose-dependent manner. The IC50 values of NCTD, NCTD-PVA and NCTD-CS on ECA-109 cell at 48 h were 9.4 ± 0.9, 55.3 ± 3.0 and 168.8 ± 8.9 μg/ml, respectively, and the IC50 values of the three compounds on EMT6 cell were 3.1 ± 0.3, 30.5 ± 5.4 and 90.7 ± 8.1 μg/ml, respectively. The two conjugates both induced esophageal carcinoma ECA-109 cell apoptosis and arrested cell cycle at the S phase. Caspase-8 and caspase-3 were activated in the ECA-109 cell after incubating with NCTD-PVA or NCTD-CS. The primary in vivo antitumor activity was assessed in the EMT6 tumor-bearing mouse model. NCTD-PVA and NCTD-CS displayed higher tumor inhibition rates than that of free NCTD.