Detecting and quantifying intracellular microRNAs(miRNAs)are a critical step in resolving a cancer diagnostic and resolving the ensemble of gene products that orchestrate the living state of cells.However,the nanoprob...Detecting and quantifying intracellular microRNAs(miRNAs)are a critical step in resolving a cancer diagnostic and resolving the ensemble of gene products that orchestrate the living state of cells.However,the nanoprobe for detecting low abundance miRNAs in cell cytosol is restricted by either the"one-to-one"signaltrigger model or di culty for cytosol delivery.To address these challenges,we designed a lightharvesting nanoantenna-based nanoprobe,which directs excitation energy to a single molecule to sensitively detect cytosolic miRNA.With light irradiation,the light-harvesting nanoantenna e ectively disrupted lysosomal structures by generationof reactive oxygen species,substantially achieved cytosol delivery.The nanoantenna containing>4000 donor dyes can e ciently transfer excitation energy to one or two acceptors with 99%e ciency,leading to unprecedented signal amplification and biosensing sensitivity.The designed nanoantenna can quantify cytosolic miR-210 at zeptomolar level.The fluorescence lifetime of the donor exhibited good relationship with miR-210 concentration in the range of 0.032 to 2.97 amol/ngRNA.The zeptomole sensitivity of nanoantenna provides accurate bioimaging of miR-210 both in multiple cell lines and in vivo assay,which creates a pathway for the creation of miRNA toolbox for quantitative epigenetics and personalized medicine.展开更多
Chemodynamic therapy(CDT)based on nanozyme has received much attention for safe and effective cancer treatment.However,the catalytic ability of nanozyme and insufficient intracellular H_(2)O_(2) levels severely limit ...Chemodynamic therapy(CDT)based on nanozyme has received much attention for safe and effective cancer treatment.However,the catalytic ability of nanozyme and insufficient intracellular H_(2)O_(2) levels severely limit their therapeutic effect.To overcome these limitations,we construct tumor microenvironment-responsive hybrid cascade systems,where single-atom Cu nanozymes(CuNC SANs)with high peroxidase(POD)-like activity were synthesized to immobilize glucose oxidase(GOx).To enhance their biological performance and stability,polyethylene glycol(DSPE-PEG-NH_(2))is further modified.After endocytosis into tumor cells,the immobilized GOx of cascade systems reacts with intracellular glucose to produce H_(2)O_(2) in situ.The H_(2)O_(2) with elevated concentration can be further catalyzed by CuNC SANs and increase ROS yield after cascade reaction,thus amplifying the effect of CDT.In addition,the consumption of glucose cuts off the energy supply of the tumor,realizing starvation therapy.Significantly,the photothermal properties of CuNC SANs not only accelerate the cascade reaction but also enable photothermal therapy(PTT)for cancer treatment.This study proposes a promising PTT/CDT/starvation triple therapy strategy for high-efficiency cancer therapy.展开更多
Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the ...Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.展开更多
Near-infrared(NIR)laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy.However,insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen(1 O2)di...Near-infrared(NIR)laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy.However,insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen(1 O2)distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes.To achieve high tumor killing efficacy,one of the solutions is to employ the combinational treatment of phototherapy with other modalities,especially with chemotherapeutic agents.In this paper,a simple and effective multimodal therapeutic system was designed via combining chemotherapy,photothermal therapy(PTT),and photodynamic therapy(PDT)to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain.IR-780(IR780)dye-labeled tube-forming peptoids(PepIR)were synthesized and self-assembled into crystalline nanotubes(PepIR nanotubes).These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density;thus,a self-quenching of these IR780 molecules was significantly reduced.Moreover,the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells.Given the unique properties of peptoids and peptoid nanotubes,we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.展开更多
Immobilizing enzymes within metal-organic frameworks(MOFs)enables enzymes to against extreme environments.However,these MOF shells are just like armors,protective but heavy,which shield the enzymes from threats while ...Immobilizing enzymes within metal-organic frameworks(MOFs)enables enzymes to against extreme environments.However,these MOF shells are just like armors,protective but heavy,which shield the enzymes from threats while locking them in the cage.The exploitation of immobilization strategy and intrinsic property of MOFs themselves is of great significance.Here,we proposed a functional protein trap strategy for efficient enzyme encapsulation.The ferrocenedicarboxylic acid(Fc)was used to induce the formation of defect-rich Co-based MOFs(CoBDC-Fc).As result,the engineered protein trap can not only improve the enzyme loading but also accelerate catalytic efficiency.Specifically,the atomically dispersed Fc sites serve as cocatalysts/cofactors and even change the conformation of enzymes in the construed microenvironment.Furthermore,the obtained CoBDC-Fc/enzyme exhibits excellent recyclability and tolerance to inhospitable conditions.Benefited by these,the CoBDC-Fc/enzyme/antigen composites were further prepared for cascade enzyme-linked immunosorbent assay of prostate-specific antigen with satisfactory sensitivity.展开更多
基金supported by start-up fund of Washington State University。
文摘Detecting and quantifying intracellular microRNAs(miRNAs)are a critical step in resolving a cancer diagnostic and resolving the ensemble of gene products that orchestrate the living state of cells.However,the nanoprobe for detecting low abundance miRNAs in cell cytosol is restricted by either the"one-to-one"signaltrigger model or di culty for cytosol delivery.To address these challenges,we designed a lightharvesting nanoantenna-based nanoprobe,which directs excitation energy to a single molecule to sensitively detect cytosolic miRNA.With light irradiation,the light-harvesting nanoantenna e ectively disrupted lysosomal structures by generationof reactive oxygen species,substantially achieved cytosol delivery.The nanoantenna containing>4000 donor dyes can e ciently transfer excitation energy to one or two acceptors with 99%e ciency,leading to unprecedented signal amplification and biosensing sensitivity.The designed nanoantenna can quantify cytosolic miR-210 at zeptomolar level.The fluorescence lifetime of the donor exhibited good relationship with miR-210 concentration in the range of 0.032 to 2.97 amol/ngRNA.The zeptomole sensitivity of nanoantenna provides accurate bioimaging of miR-210 both in multiple cell lines and in vivo assay,which creates a pathway for the creation of miRNA toolbox for quantitative epigenetics and personalized medicine.
基金the financial support from the Natural Science Foundation of Hubei Province,China(No.2023AFB122)“the 14th Five Year Plan”Hubei Provincial advantaged characteristic disciplines(groups)project of Wuhan University of Science and Technology(No.2023C0301)。
文摘Chemodynamic therapy(CDT)based on nanozyme has received much attention for safe and effective cancer treatment.However,the catalytic ability of nanozyme and insufficient intracellular H_(2)O_(2) levels severely limit their therapeutic effect.To overcome these limitations,we construct tumor microenvironment-responsive hybrid cascade systems,where single-atom Cu nanozymes(CuNC SANs)with high peroxidase(POD)-like activity were synthesized to immobilize glucose oxidase(GOx).To enhance their biological performance and stability,polyethylene glycol(DSPE-PEG-NH_(2))is further modified.After endocytosis into tumor cells,the immobilized GOx of cascade systems reacts with intracellular glucose to produce H_(2)O_(2) in situ.The H_(2)O_(2) with elevated concentration can be further catalyzed by CuNC SANs and increase ROS yield after cascade reaction,thus amplifying the effect of CDT.In addition,the consumption of glucose cuts off the energy supply of the tumor,realizing starvation therapy.Significantly,the photothermal properties of CuNC SANs not only accelerate the cascade reaction but also enable photothermal therapy(PTT)for cancer treatment.This study proposes a promising PTT/CDT/starvation triple therapy strategy for high-efficiency cancer therapy.
基金supported by the U.S.Department of Energy,Office of Basic Energy Sciences,Division of Materials Science and Engineering under an award FWP 65357 at Pacific Northwest National Laboratory(PNNL)the Cougar Cage Fund for the work of biological imaging and detection of microRNA.Development of peptoid synthesis capabilities was supported by the Materials Synthesis and Simulation Across Scales(MS3)Initiative through the Laboratory Directed Research and Development(LDRD)program at PNNL.XRD work was conducted at the Advanced Light Source(ALS)of Lawrence Berkeley National Laboratory+1 种基金supported by the Office of Science(No.DE-AC02-05CH11231)PNNL is multi-program national laboratory operated for Department of Energy by Battelle(No.DE-AC05-76RL01830).
文摘Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.
基金supported by Washington State University(WSU)start-up fund.Peptoid synthesis work was supported by the Materials Synthesis and Simulation Across Scales(MS3)Initiative through the LDRD fund at Pacific Northwest National Laboratory(PNNL)Assembly of peptoid nanotubes and their structural characterizations were supported by the U.S.Department of Energy,Office of Basic Energy Sciences,Biomolecular Materials Program at PNNL+1 种基金the Advanced Light Source with support from the Molecular Foundry,at Lawrence Berkeley National Laboratory,both of which are supported by the Office of Science,under Contract No.DE-AC02-05CH11231PNNL is a multiprogram national laboratory operated for Department of Energy by Battelle under Contract No.DE-AC05-76RL01830.
文摘Near-infrared(NIR)laser-induced phototherapy through NIR agents has demonstrated the great potential for cancer therapy.However,insufficient tumor killing due to the nonuniform heat or cytotoxic singlet oxygen(1 O2)distribution over tumors from phototherapy results in tumor recurrence and inferior outcomes.To achieve high tumor killing efficacy,one of the solutions is to employ the combinational treatment of phototherapy with other modalities,especially with chemotherapeutic agents.In this paper,a simple and effective multimodal therapeutic system was designed via combining chemotherapy,photothermal therapy(PTT),and photodynamic therapy(PDT)to achieve the polytherapy of malignant glioma which is one of the most aggressive tumors in the brain.IR-780(IR780)dye-labeled tube-forming peptoids(PepIR)were synthesized and self-assembled into crystalline nanotubes(PepIR nanotubes).These PepIR nanotubes showed an excellent efficacy for PDT/PTT because the IR780 photosensitizers were effectively packed and separated from each other within crystalline nanotubes by tuning IR780 density;thus,a self-quenching of these IR780 molecules was significantly reduced.Moreover,the efficient DOX loading achieved due to the nanotube large surface area contributed to an efficient and synergistic chemotherapy against glioma cells.Given the unique properties of peptoids and peptoid nanotubes,we believe that the developed multimodal DOX-loaded PepIR nanotubes in this work offer great promises for future glioma therapy in clinic.
基金support of the National Natural Science Foundation of China(Nos.22074049 and 22004042)the Fundamental Research Funds for the Central Universities(No.CCNU22JC006)the Program of Introducing Talents of Discipline to Universities of China(111 program,No.B17019).
文摘Immobilizing enzymes within metal-organic frameworks(MOFs)enables enzymes to against extreme environments.However,these MOF shells are just like armors,protective but heavy,which shield the enzymes from threats while locking them in the cage.The exploitation of immobilization strategy and intrinsic property of MOFs themselves is of great significance.Here,we proposed a functional protein trap strategy for efficient enzyme encapsulation.The ferrocenedicarboxylic acid(Fc)was used to induce the formation of defect-rich Co-based MOFs(CoBDC-Fc).As result,the engineered protein trap can not only improve the enzyme loading but also accelerate catalytic efficiency.Specifically,the atomically dispersed Fc sites serve as cocatalysts/cofactors and even change the conformation of enzymes in the construed microenvironment.Furthermore,the obtained CoBDC-Fc/enzyme exhibits excellent recyclability and tolerance to inhospitable conditions.Benefited by these,the CoBDC-Fc/enzyme/antigen composites were further prepared for cascade enzyme-linked immunosorbent assay of prostate-specific antigen with satisfactory sensitivity.
