An activatable theranostic for targeted cancer therapy and imaging

A new theranostic strategy is described. It is based on the use of an "all in one" prodrug, namely the biotinylated piperazine-rhodol conjugate 4 a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1 a. This release is made selective as the result of the biotin functionality. Fluorophore 1 a is 32-fold more fluorescent than prodrug 4 a. It permits the delivery and release of the SN-38 payload to be monitored easily in?vitro and in?vivo, as inferred from cell studies and ex?vivo analyses of mice xenografts derived from HeLa cells, respectively. Prodrug 4 a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy. All in one: A new theranostic prodrug was developed containing a biotinylated piperazine-rhodol conjugate linked to the drug SN-38 through a self-immolative disulfide spacer. When exposed to cellular thiols in cancer cells, it is able to release the active chemotherapeutic, SN38, along with a diagnostic fluorophore. This theranostic framework permits the targeted delivery, release of an active agent (SN-38), and its facile monitoring in vitro and in vivo.