Dual-stimuli Responsive Fluorescent Nanoprobes For Hypoxia Imaging In Tumor

Cancer is one of the main factors that threaten the quality of human life.M utations leads the cell to grow out of control and clump together,suggesting they form tumors.Hypoxia is caused by the exaggerated growth of solid t u m o r w h e r e t h e d e p l e t i o n o f o x y g e n i n i n t e r i o r c e l l s f a r e x c e e d s t h e i r b l o o d s u p p l y.I n o r d e r t o a d a p t t h e harsh environment,tumor cells would undergo change of metabolism and genetic alterations.Therefore,imaging for hypoxiainduced changes in tumor cells is an essential tool for cancer diagnosis and treatment.Based on the nanomaterial science and fluorescence imaging technology,many fluorescent nanoprobes for hypoxia-responsive imaging have been developed until now.Compared with the single-stimulusresponsive imaging,though dual-stimuli-responsive nanoprobe is complicated,the fluorescence imaging result is more accurate.Thus,we complete the following works in the article:1.Azoreductase and ATP dual-stimuli-responsive fluorescent nanoprobe for hypoxia imaging in living cells.In this chapter,an azoreductase and ATP dual responsive fluorescent nanoprobe for imaging hypoxic cells was constructed.First,we designed an Cy5 modified-DNA sequence S1 which contained ATP aptamer,S1 would form a hairpin structure after annealing.Then,we designed a DNA sequence S2 with a sulfhydryl group labelled at the end,and a DNA sequence S3 with azobenzene and TAMRA modified at the end.Doubled-stranded S1S2 could modified on the surface of Au NPs through Au-S bond,and single strand S3 could modified on the surface of Au NPs via host-guest interaction between azobenzene and SH-β-CD.Under normoxic conditions,ATP would recognize the ATP aptamer in S1,resulting the fluorescence of Cy5 switched “on”.Upon entering hypoxic cells,the azo linkage of S3 was reduced to amines by azoreductase,which could result in the release of S3 accomp anied by fluorescence recovery of TAMRA.On the basis of that,imaging for hypoxic cells could be realized by detecting the fluorescence of TAMRA and Cy5.2.Hypoxia and pH dual-stimuli-responsive fluorescent nanoprobe for hypoxia imaging in tumor.In this chapter,a hypoxia/pH dual stimuli responsive fluorescent nanoprobe for specific tumor imaging was constructed.First,mesoporous silica coated gold nanorods was selected as nanocarrier,with modification of azobenzene to response to hypoxia.Subsequently,pH-sensitive fluorescent dye Rho-TP were loaded into mesoporous and β-CDP were modified on the surface of nanoparticles to serve as gatekeeper.After the nanoprobe internalizing into hypoxic cells,the highly expressed azoreductase would reduce the azo linkage to amino derivatives and thus release encapsulated Rho-TP from nanocarrier,which finally result in measurable fluorescent signal with altered pH values.By combination hypoxia responsive azo/β-CDP with pH responsive Rho-TP,specific imaging of tumor would be realized.