期刊
BIOMATERIALS
卷 104, 期 -, 页码 297-309出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.07.024
关键词
Theranostic; Ratiometric imaging; Apoptosis imaging; FRET; Photodynamic therapy
资金
- National Natural Science Foundation of China [51233003, 21474077, 51533006]
- Fundamental Research Funds for the Central Universities [2014203020204, 2014203020201]
Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Forster 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 4133 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. (C) 2016 Elsevier Ltd. All rights reserved.
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