β-Glucuronidase-Responsive Albumin-Binding Prodrug of Colchicine-Site Binders for Selective cancer Therapy

The development of novel therapeutic strategies enabling the selective destruction of tumors while sparing healthy tissues is of great interest to improve the efficacy of cancer chemotherapy. In this context, we designed a β-glucuronidase-responsive albumin-binding prodrug programmed to release a potent Isocombretastatin A-4 analog within the tumor microenvironment. When injected at a non-toxic dose in mice bearing orthotopic triple-negative mammary tumors, this prodrug produced a significant anticancer activity, therefore offering a valuable alternative to the systemic administration of the parent drug.