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
The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations ...The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.展开更多
Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to...Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to be loaded into a nanocarrier for tumor targeted delivery,which consequently encounters poor drug loading,heterogeneous composition and non-encapsulated drug aggregates occurred during nanoformulation fabrications.Herein,a nitroreductase(NTR)-activated“OFF-ON”near-infrared fluorescence nanoprobe,named Nano Bodipy,was synthesized by the spontaneous self-assembling of NTRresponsive dye-polyethylene glycol(PEG)amphiphilic polymer in water.The NTR-responsive dye acted as the hydrophobic segment in the amphiphilic polymer,yielding a homogeneous composition and a high loading of 12.2 wt%(according to calculation)in the synthesized Nano Bodipy.The synthesized Nano Bodipy can efficiently accumulate in tumors via the enhanced permeability and retention(EPR)effect,enabling non-invasive tumor-targeted fluorescence imaging and guiding complete tumor resection.Once the synthesized Nano Bodipy entered the tumor cells,they dissociated and were activated by overexpressed NTR.With the real-time fluorescence guide of Nano Bodipy,complete tumor resection surgery was performed successfully.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the National Natural Science Foundation of China(Nos.81903662,51903201)China Postdoctoral Science Foundation Grant(Nos.2019M661057,2019M653660)+5 种基金the Applied Basic Research Programs of Shanxi Province(No.201901D211347)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0428)the Startup Foundation for Doctors of Shanxi Province(No.SD1827)Natural Science Foundation of Shaanxi Province(No.2020JQ-086)College Students’Innovation and Entrepreneurship Training Program(No.SJ201910698121)the Startup Foundation for Doctors of Shanxi Medical University(No.XD1824)。
文摘The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.51903201,82172798)the Natural Science Foundation of Shaanxi Province(No.2023-YBSF-270)+1 种基金the Open Program of NHC Key Laboratory of Nuclear Medicine and Jiangsu Key Laboratory of Molecular Nuclear Medicine(No.KF202203)Horizontal Project of the First Affiliated Hospital of Xi'an Jiaotong University(No.202304174)。
文摘Tumor microenvironment(TME)-activatable probes have been proven to effectively increase signal-tobackground ratios(SBRs)and improve the success rate of complete tumor resection.However,many fluorescence probes have to be loaded into a nanocarrier for tumor targeted delivery,which consequently encounters poor drug loading,heterogeneous composition and non-encapsulated drug aggregates occurred during nanoformulation fabrications.Herein,a nitroreductase(NTR)-activated“OFF-ON”near-infrared fluorescence nanoprobe,named Nano Bodipy,was synthesized by the spontaneous self-assembling of NTRresponsive dye-polyethylene glycol(PEG)amphiphilic polymer in water.The NTR-responsive dye acted as the hydrophobic segment in the amphiphilic polymer,yielding a homogeneous composition and a high loading of 12.2 wt%(according to calculation)in the synthesized Nano Bodipy.The synthesized Nano Bodipy can efficiently accumulate in tumors via the enhanced permeability and retention(EPR)effect,enabling non-invasive tumor-targeted fluorescence imaging and guiding complete tumor resection.Once the synthesized Nano Bodipy entered the tumor cells,they dissociated and were activated by overexpressed NTR.With the real-time fluorescence guide of Nano Bodipy,complete tumor resection surgery was performed successfully.
