Floxuridine-chlorambucil conjugate nanodrugs for ovarian cancer combination chemotherapy

Due to no specific symptoms and lack of early diagnosis for ovarian cancer, most diagnosed patients are often in the terminal stage resulting that tumor tissue is unable to be resected completely by operation. So postoperative chemotherapy has become an important and indispensable treatment procedure for them. Up to date, it remains a challenge to treat ovarian cancer by an effective chemotherapy strategy. Recently, the strategy of ADDC has been regarded as a highly effective chemotherapy strategy to treat various cancers without any drug carriers. Here a novel ADDC is synthesized by linking a water-soluble antitumor drug floxuridine (Fud) and a water-insoluble antitumor drug chlorambucil (Cb) through the esterification. Then the Fud-Cb conjugate can form stable nanodrugs in water with an average size around 103.0 nm through molecular self-assembly. After internalization of cells, the ester bonds in nanodrugs can be degraded to release free Fud and Cb at a fixed ratio under the intracellular acid conditions, which exhibits the high synergistic effect on ovarian cancer cells. The cytotoxicity test results show that Fud-Cb nanodrugs can efficiently inhibit the growth of ovarian cancer cells. The apoptosis data exhibit that the cell necrotic and apoptotic rate treated with Fud-Cb nanodrugs is about 73.7 % and 18.76 % within 24 h. These results suggest that Fud-Cb nanodrugs based on ADDC strategy can effectively enhance synergistic anticancer efficacy to ovarian cancer.