Self-assembling CPT-drug Amphiphiles for Cancer Treatment

Unmet need: DNA topoisomerases have become a widely exploited chemotherapeutic drug target for the treatment of advanced cancer. Multiple classes of topoisomerase inhibitors have been marketed including camptothecin (CPT) derivatives. However, while these analogues are less toxic than CPT, they are have reduced efficacy due to their prodrug formulation, poor solubility and poor accumulation within tumors, and may lead to development of drug resistance. Consequently, there is a need for improved CPT-derived products with higher efficacy and no enhanced toxicity.
 
Technology overview: JHU researchers have designed self-assembling CPT analogues, termed Tubustecans (TTs), which upon dissolution in aqueous solutions assemble into tubular supramolecular polymers that mask the pharmaceutical nature of the unassembled CPT. Upon dissociation in biologically relevant environments, the CPT activity is effectively restored.  In vivo studies in models of glioma, lung, colon and breast cancers have shown enhanced stability, reduced toxicity, and enhanced efficacy compared to an existing CPT-based therapy irinotecan.
 
Inventors: Honggang Cui, Hao Su, Feihu Wang

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