title: Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy.
abstract: Herein we describe the design and synthesis of a folate-doxorubicin conjugate with activatable fluorescence and activatable cytotoxicity. In this study we discovered that the cytotoxicity and fluorescence of doxorubicin are quenched (OFF) when covalently linked with folic acid. Most importantly, when the conjugate is designed with a disulfide bond linking the targeting folate unit and the cytotoxic doxorubicin, a targeted activatable prodrug is obtained that becomes activated (ON) within the cell by glutathione-mediated dissociation and nuclear translocation, showing enhanced fluorescence and cellular toxicity. In our novel design, folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin's fluorescence.
authors.affiliation: NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, Florida 32816, USA.
authors.forename: Santimukul
authors.initials: S
authors.lastname: Santra
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kaittanis
authors.forename: Oscar J
authors.initials: OJ
authors.lastname: Santiesteban
authors.forename: J Manuel
authors.initials: JM
authors.lastname: Perez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D005492:Folic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D004317:Doxorubicin; D005492:Folic Acid