An albumin-binding lidamycin prodrug for efficient targeted cancer therapy

As a radiomimetic antitumor antibiotic, lidamycin (LDM) contains an enediyne chromophore and an apoprotein LDP. Potent cytotoxicity and lack of tumor localization limited its clinical application. Though a series of fusion proteins composed of LDM and tumor-targeting moieties has been prepared and ameliorated LDM's antitumor activity, the complicated preparation process and the low reconstitution efficacy of chromophore limited their developments. Here, we report an albumin-binding LDM prodrug for efficient targeted cancer chemotherapy. LDM or rLDP (recombinant LDP) was modified with Sulfo-SMCC to produce Mal-LDM and Mal-rLDP by a one-step reaction. LC-MS assay demonstrated that one maleimide group was successfully conjugated to rLDP. Mal-rLDP bound to albumin quickly in vitro and in vivo. After intravenous injection, Cy7-labelled Mal-rLDP mainly localized at the tumor site and displayed extended serum half-life. Mal-LDM showed similar cytotoxicity compared with LDM in vitro. In vivo, Mal-LDM showed increased antitumor activity and decreased cytotoxicity compared with LDM. All of those results demonstrate that Mal-LDM is a promising prodrug which could be used in clinic after a simple modification of LDM.