| Optical imaging probes can detect and visualize subtle molecular changes with high sensitivity and specificity,so they are of importance in the field of sensing and biological imaging.Among these probes,fluorescent probes have a poor ability to image deep tissue in vivo due to their shallow imaging penetration depth resulted from light scattering by tissues;but fluorescence imaging possesses high sensivitity.By constrast,photoacoustic imaging is a kind of hybrid imaging methods,it adopts optical excitation but detects ultrasound signals instead of photons,as the tissues' scattering of ultrasound is negligible,the imaging depth of photoacoustic imaging is much larger compared to fluorescence imaging.The integration of fluorescence imaging and photoacoustic imaging would combine the advantages of both imaging modalities,thus enabling fluorescent/photoacoutic dual-mode imaging.Activatable probes can correlate signals with the concentration or activity of biomarkers for detection or imaging.However,the existing probes have some shortcomings,such as aggregation-caused quenching(ACQ)and non-evident signal change before and after response,which make high-performance dual-mode fluorescent/photoacoustic imaging impossible.To overcome these limitations,three kinds of activatable probes with xanthene and its derivatives as electron donor have been designed and prepared in this study,and their applications in imaging have been investigated.The main contents are as follows:(1)Quinone oxidoreductase(NQO1)– responsive nanoprobe based on xanthene.The chromophore with aggregation-induced emission feature has been designed and prepared with diphenylamine-modified xanthene derivative as the electron donor and indolium as the electron acceptor,the emission wavelength is up to 730 nm.Afterwards,the quinone propionic acid has been incorporated into the chromophore through esterification reaction,and thus offering the probe compound DHXI.Upon the self assembly of the probe compound and recombinant human serum albumin,quinone oxidoreductase(NQO1)-activatable nanoprobe DHXI@HSA form.The response of the nanoprobe to NQO1 in solution has been investigated by absorption spectroscopy,photoacoustic spectroscopy and fluorescence spectroscopy.Orthotopic liver cancer mouse model has been employed to investigate the nanoprobe's imaging ability of tumors via responding to NQO1 in vivo.Furthermore,breast cancer peritoneal metastasis mouse model has been adopted to evaluate the capability of the probe for fluorescence-guided tumor resection.(2)Hydrogen-peroxide-responsive nanoprobe based on xanthene.The chromophore TPEXI-OH with aggregation-induced emission has been designed and prepared with triphenylethylene-modified xanthene as the electron donor,its emission wavelength is up to720 nm.The hydrogen peroxide recognition moiety,phenyl boronic acid has been incorporated into the chromophore to obtain the probe compound TPEXI.Afterwards,through the complexation between the probe compound and natural polyphenol,the nanoprobe TPEXI@EGCG has been obtained.The response of nanoprobe has been evaluated by absorption spectroscopy,photoacoustic spectroscopy and fluorescence spectroscopy.The drug-induced liver injury mouse model and the diabetes-induced liver injury mouse model have been used to explore the imaging ability of the nanoprobe.(3)Azoreductase-responsive nanoprobe based on xanthene.The probe compound with xanthene as the electron donor has been designed and prepared.Through diazotization reaction,the phenyl nitrogen mustard(chemotherapy drug)has been introducted into the probe compound via an azo bond to obtain the prodrug XI-azo,After activation,the absorption spectra redshift by 100 nm,and the fluorescence intensity enhance by 200 times.Upon encapsulation of the prodrug by lipid,the liposomal nanoprodrug Lip@XI-azo has been prepared.The subcutaneous tumor mouse model has been adopted to investigate the imaging and tumor suppression ability of the nanoprodrug. |
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