Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity.

To enhance the selective delivery of antitumor drugs into regional lymph nodes and cancerous tissues via a hyaluronate (HA) receptor (CD44), we synthesized HA-mitomycin C complex and HA-epirubicin complex. To investigate the specific distribution of HA into regional lymph nodes and to evaluate the HA receptor on lewis lung carcinoma cells, we also synthesized 14C-labelled HA and fluorescent HA (FR-HA). The metabolic studies of 14C-HA and HA-epirubicin complex were performed in rats. The specific distribution of both compounds to the lymph nodes were observed after sc treatment. Internalization mechanisms of HA into carcinoma cells (lewis lung carcinoma) via HA receptor was investigated using fluorescent HA (FR-HA) in vitro. Internalization of FR-HA following binding to the cell surfaces was observed. HA-Mitomycin C (MMC) exhibited potent anti-metastatic effects against lewis lung carcinoma implanted in mice at an extremely low dose (0.01 mg/kg) whereas free MMC had no effects.