Development of High Loading β-Lapachone Prodrug Micelles for NQO1-Specific Cancer Therapy

摘要

A series of β-lap prodrugs with diester structures were prepared from β-lap. Prodrugs and PEG-PLA formed nanosized micelles with high drug loading efficiency (up to ～100%) and loading density (up to 20 wt%). The micelles achieved high apparent solubility of β-lap in solution (>7 mg/mL). Prodrugs alone or micelle-delivered prodrugs can easily be converted to its parent drug β-lap in the presence of PLE. In vitro cytotoxicity data showed that after 2 h incubation, prodrug micelles had a significant increase of toxicity in NQO1+ cells compared to NQO1- lung cancer cells. Currently, drug pharmacokinetics, in vivo target validation, and antitumor efficacy measurements in athymic nude mice bearing orthotopic and subcutaneous tumor xenografts are ongoing.