title: Modular theranostic prodrug based on a FRET-activated self-immolative linker.
abstract: New chemotherapeutic prodrugs that can report on the localization and activation of the drug upon internalization into select cells are being widely investigated for cancer treatment. Here, we introduce a new molecular design for a theranostic prodrug based on a self-immolative linker attached to a pair of FRET dyes that produces a fluorescent signal upon disassembly. The prodrug evaluated here was designed to release the chemotherapeutic drug camptothecin upon activation by the model enzyme penicillin-G-amidase. Similar patterns of the disassembly of the prodrug were observed in HPLC and fluorescence assays. The obtained results demonstrate that upon specific activation of the prodrug, the increase of the emitted fluorescent signal is linearly correlated with the observed drug release. Such a design could potentially be used to monitor prodrug activation in real-time and provide information regarding the location and the amount of active drug molecules.
authors.affiliation: School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Redy
authors.forename: Doron
authors.initials: D
authors.lastname: Shabat
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D016903:Drug Monitoring / Q000379:methods*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D010399:Penicillin Amidase / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D011355:Prodrugs; D010399:Penicillin Amidase; D002166:Camptothecin