Abstract
Mitoxantrone (MTO) is an anthraquinone antitumor drug with potent therapeutic benefits. However, its clinical application is restricted by the severe side effects stemming from poor tumor selectivity. In this study, MTO and cholesterol (CLS) were conjugated via a tumor-selective disulfide bond to obtain the MTO-SS-CLS prodrug. Interestingly, the MTO-SS-CLS could self-assemble into uniform nanoassemblies, and the addition of DSPE-PEG2K significantly improved its self-assembly behavior and stability. Moreover, compared with MTO solutions, the disulfide bond-bridged MTO-SS-CLS nanoassemblies exhibited heightened tumor selectivity and pharmacokinetic properties. In addition, the prodrug nanoassemblies improved the tolerated dose and safety of MTO without compromising its therapeutic effect. This research enriches the pharmaceutical research of MTO and paves the way for its extensive clinical application.
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