title: An activatable theranostic for targeted cancer therapy and imaging.
abstract: 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.
authors.affiliation: Division of MR Research, Korea Basic Science Institute, Cheongwon 363-883 (Korea).
authors.forename: Sankarprasad
authors.initials: S
authors.lastname: Bhuniya
authors.forename: Sukhendu
authors.initials: S
authors.lastname: Maiti
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D057054:Molecular Imaging; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D011355:Prodrugs; D013438:Sulfhydryl Compounds; D000077146:Irinotecan; D002166:Camptothecin
keywords: SN-38; biotin; cellular imaging; glutathione; theranostic