The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emi...The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emission spectra and a short Stokes shift,which may lead to overlap with bioautofluorescence,excitation,and emission spectra,limiting their use in intraoperative guidance.Herein,aγ-glutathione(GSH)responsive near-infrared(NIR)BODIPY probe,named“Pro-Dye”was synthesized with a large Stokes shift of 91 nm.The Pro-Dye can be rapidly and specifically activated by high concentrations of GSH both in solution and inside cancer cells,while remaining inactive in normal cells(Human umbilical vein endothelial cells,HUVECs).The Pro-Dye was further encapsulated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)-5000(DSPE-PEG5000)to form Pro-Dye nanoparticles(NPs),making it water-dispersible for in vivo application.In vivo fluorescence imaging demonstrated that Pro-Dye NPs can accumulate at the tumor and exhibit an improved SBR compared to the“alwayson”probe(Dye NPs).Moreover,the tumor can be precisely resected under the real-time guidance of fluorescence imaging of Pro-Dye NPs,showing a well-defined tumor margin.展开更多
Glioma is the most malignant brain cancer.The neurons,macrophages,T cells and other immune ellls constitute the glioma immunosuppressive microenvironment.The accurate spatial distri-bution of these cells in the glioma...Glioma is the most malignant brain cancer.The neurons,macrophages,T cells and other immune ellls constitute the glioma immunosuppressive microenvironment.The accurate spatial distri-bution of these cells in the glioma microenvironment and its relationship with glioma metastasis is unknown.We constructed a mouse gliomna cell line stably expressing the large Stokes shifted yellow fluorescent protein and applied it to the multicolor immunofluorescence imaging.The inaging data revealed that the neurons were sparsely distributed in the glioma core and the mumber of neurons decreased by 90%compared with normal brain site.The spatial distribution of monocyte-macrophages and microglia is heterogeneous.The monocyte macrophages and T cells were heavily recrnuited into the glioma core and metastasis.There was no significant difference in the distribution of microglia amnong glioma core,margin,and normal brain site.Our results provided new perspectives for targeting immune regulation cells and developing new immuno-therapy strategies for glioma.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province(Nos.2023-YBSF-270,2024SF-ZDCYL-02-08)Fundamental Research Funds for the Central Universities(No.xzy022024033)+2 种基金Horizontal Project of the First Affiliated Hospital of Xi’an Jiaotong University(No.202304174)supported by the Opening Project of Structural Optimization and Application of Functional Molecules Key Laboratory of Sichuan Province(No.2023GNFZ-03)The Key Laboratory for Screening and Diagnosis of Maternal and Child Genetic Disease of Health Commission of Jiangxi Province.
文摘The tumor microenvironment(TME)-activatable probes have proven effective in enhancing the signalto-background ratio(SBR)for precise fluorescence imaging in tumor diagnosis.However,many fluorophores have suboptimal emission spectra and a short Stokes shift,which may lead to overlap with bioautofluorescence,excitation,and emission spectra,limiting their use in intraoperative guidance.Herein,aγ-glutathione(GSH)responsive near-infrared(NIR)BODIPY probe,named“Pro-Dye”was synthesized with a large Stokes shift of 91 nm.The Pro-Dye can be rapidly and specifically activated by high concentrations of GSH both in solution and inside cancer cells,while remaining inactive in normal cells(Human umbilical vein endothelial cells,HUVECs).The Pro-Dye was further encapsulated by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)-5000(DSPE-PEG5000)to form Pro-Dye nanoparticles(NPs),making it water-dispersible for in vivo application.In vivo fluorescence imaging demonstrated that Pro-Dye NPs can accumulate at the tumor and exhibit an improved SBR compared to the“alwayson”probe(Dye NPs).Moreover,the tumor can be precisely resected under the real-time guidance of fluorescence imaging of Pro-Dye NPs,showing a well-defined tumor margin.
基金supported by the National Natural Science Foundation of China (31700808)the Fundamental Research Funds for the Central Universities (2020kfyXJJS112).
文摘Glioma is the most malignant brain cancer.The neurons,macrophages,T cells and other immune ellls constitute the glioma immunosuppressive microenvironment.The accurate spatial distri-bution of these cells in the glioma microenvironment and its relationship with glioma metastasis is unknown.We constructed a mouse gliomna cell line stably expressing the large Stokes shifted yellow fluorescent protein and applied it to the multicolor immunofluorescence imaging.The inaging data revealed that the neurons were sparsely distributed in the glioma core and the mumber of neurons decreased by 90%compared with normal brain site.The spatial distribution of monocyte-macrophages and microglia is heterogeneous.The monocyte macrophages and T cells were heavily recrnuited into the glioma core and metastasis.There was no significant difference in the distribution of microglia amnong glioma core,margin,and normal brain site.Our results provided new perspectives for targeting immune regulation cells and developing new immuno-therapy strategies for glioma.
