title: A ratiometric theranostic probe for tumor targeting therapy and self-therapeutic monitoring.
abstract: Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Förster resonance energy transfer (FRET) based theranostic probe was fabricated for simultaneous tumor targeting PDT and ratiometric imaging of the therapeutic effect. The theranostic probe (designated as P-PpIX) was comprised of a targeting moiety, a caspase-3 responsive linker, a FRET fluorophore pair and a photosensitizer. It was found that P-PpIX exhibited low intrinsic background fluorescence due to the high FRET quenching efficiency. The Arg-Gly-Asp (RGD) targeting moiety allowed P-PpIX to selectively accumulate in αvβ3 integrin overexpressed tumor cells. Upon photo irradiation, the PDT effect of P-PpIX could induce cell death with apoptosis related mechanism, and the activated caspase-3 would subsequently cleave the Asp-Glu-Val-Asp (DEVD) peptide sequence to terminate the intramolecular FRET process. The activated caspase-3 expression and the real time therapeutic efficacy could be precisely assessed in situ by the fluorescence intensity ratio of the released 5(6)-carboxylfluorescein (FAM, reporter fluorescence) and protoporphyrin IX (PpIX, internal reference fluorescence). This novel ratiometric theranostic probe could provide the real-time feedback for precise PDT.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Li
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Bo-Ru
authors.initials: BR
authors.lastname: Xie
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Wen-Xiu
authors.initials: WX
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Song
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies & Department of Chemistry, Wuhan University, Wuhan 430072, China. Electronic address: xz-zhang@whu.edu.cn.
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016903:Drug Monitoring / Q000379:methods; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D053769:Nanocapsules; D009842:Oligopeptides; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C047981:arginyl-glycyl-aspartic acid; C028025:protoporphyrin IX
keywords: Apoptosis imaging; FRET; Photodynamic therapy; Ratiometric imaging; Theranostic