Cadmium ion(Cd^(2+))detection technology plays a prominent role in food safety and human health.Herein,we designed and constructed an 2-aminoethyl dihydrogen phosphate(AEP)@upconversion nanoparticles(UCNPs)fluorescenc...Cadmium ion(Cd^(2+))detection technology plays a prominent role in food safety and human health.Herein,we designed and constructed an 2-aminoethyl dihydrogen phosphate(AEP)@upconversion nanoparticles(UCNPs)fluorescence sensor for quantitative detection of Cd^(2+)in paddy rice based on inner filter effect(IFE)combined with enzyme inhibition mechanism.The AEP modification UCNPs can offer a stable fluorescence donor at 658 nm and be quenched by the oxidized tetramethylbenzidine(oxTMB)catalyzed by horseradish peroxidase(HRP)enzymes.Without addition of Cd^(2+),the fluorescence of AEP@UCNPs fluorescence sensor was weaken due to the IFE between AEP@UCNPs and oxTMB.With addition of Cd^(2+),HRP enzyme activity was inhibited by Cd^(2+),leading to the decreased oxTMB,resulting in the enhance upconversion fluorescence intensity.As a result,the fluorescence intensity signal at 658 nm of the IFE-based AEP@UCNPs fluorescence sensor increased linearly with the increase in Cd^(2+)in a wide range from 0.5μmol/L to 6μmol/L and the limit of detection(LOD)was 24.6 n mol/L.In addition,our proposed IFE-based AEP@UCNPs fluorescence sensor can achieve Cd^(2+)detection in paddy rice in 30 min.展开更多
As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant chal...As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.展开更多
目的:构建基于上转换光学成像/磁共振成像(UCL/MRI)的纳米材料UCNP-PEG-Trastuzumab,探讨其用于HER2高表达人乳腺癌细胞SKBR3的多模态显像研究。方法:采用课题组前期制备稀土掺杂钆的上转换纳米粒子(UCNP)与HER2受体特异结合的抗体曲妥...目的:构建基于上转换光学成像/磁共振成像(UCL/MRI)的纳米材料UCNP-PEG-Trastuzumab,探讨其用于HER2高表达人乳腺癌细胞SKBR3的多模态显像研究。方法:采用课题组前期制备稀土掺杂钆的上转换纳米粒子(UCNP)与HER2受体特异结合的抗体曲妥单抗(Trastuzumab)的偶联获得UCL/MRI靶向探针。以高表达HER2受体的人乳腺癌细胞SKBR3细胞为观察对象,通过噻唑蓝比色法(MTT)进行细胞毒性检测。加入靶向探针UCNP-PEG-Trastuzumab共同孵育作为实验组,细胞加入UCNP-PEG共同孵育作为对照组,不添加任何探针的细胞作为空白组,利用共聚焦显微镜和MRI进行体外细胞成像;进行视觉分析与比较各组细胞光学和MRI信号,检测其结合效率。结果:1透射电子显微镜下(TEM),UCNP呈球形颗粒状,粒径约60nm;在980nm波长光激发下,发出绿色的荧光;2体外毒性试验MTT结果表明UCNP-PEG对SKBR3细胞毒性较小;320μg/m l浓度的UC N P-PEG-Tr a st u z u m ab与SK BR 3细胞孵育30分钟后,UCL/M R I成像结果均显示UC N P-PEGTrastuzumab能与SKBR3细胞靶向性结合。结论:构建HER2受体靶向特异性探针UCNP-PEG-Trastuzumab,能在体外与目的细胞特异性结合。展开更多
Ultraviolet(UV)phototherapy stands as a pivotal clinical approach for managing diverse skin diseases.However,its application is constrained by concerns over UV-induced toxicity and imprecise photosensitizer delivery.T...Ultraviolet(UV)phototherapy stands as a pivotal clinical approach for managing diverse skin diseases.However,its application is constrained by concerns over UV-induced toxicity and imprecise photosensitizer delivery.This work introduces a light-converting microneedle patch(EU-MN),exemplified by its remarkable efficacy in psoriasis treatment.The EU-MN patch could release upconversion nanoparticles(UCNPs)and the photosensitizer methoxypsoralen(MOP)in controlled amounts in response to elevated matrix metalloproteinase(MMP)levels within the skin.Under near-infrared(NIR)excitation,UCNPs emit UV light(345/361 nm),which is combined with MOP to achieve more precise intradermal UV photoche-motherapy,effectively inhibiting abnormal proliferation of human immortalized epidermal cells(HaCaT)and bacterial growth(Staphylococcus aureus and Escherichia coli).Comet assay highlights DNA damage correlation.In addition,the microneedles,designed with a reactive oxygen species(ROS)-responsive shell,release epigallocatechin gallate(EGCG)to counteract excessive inflammation and mitigate UV-induced damage.In psoriasis mice,the EU-MN patch demonstrates significant therapeutic efficacy and recurrence prevention.As further evidenced by the suppression of epidermal hyperplasia and inflammation(through RNA sequencing identifying cell cycle arrest),this EU-MN patch offers a safer,more precise,and more effective alternative strategy for conventional direct UV phototherapy.展开更多
The nanoplatforms based on upconversion nanoparticles(UCNPs)have shown great promise in amplified photodynamic therapy(PDT)triggered by near-infrared(NIR)light.However,their practical in vivo applications are hindered...The nanoplatforms based on upconversion nanoparticles(UCNPs)have shown great promise in amplified photodynamic therapy(PDT)triggered by near-infrared(NIR)light.However,their practical in vivo applications are hindered by the overheating effect of 980 nm excitation and low utilization of upconversion luminescence(UCL)by photosensitizers.To solve these defects,core-satellite metal-organic framework@UCNP superstructures,composed of a single metal-organic framework(MOF)NP as the core and Nd3+-sensitized UCNPs as the satellites,are designed and synthesized via a facile electrostatic self-assembly strategy.The superstructures realize a high co-loading capacity of chlorin e6(Ce6)and rose bengal(RB)benefitted from the highly porous nature of MOF NPs,showing a strong spectral overlap between maximum absorption of photosensitizers and emission of UCNPs.The in vitro and in vivo experiments demonstrate that the dual-photosensitizer superstructures have trimodal(magnetic resonance(MR)/UCL/fluorescence(FL))imaging functions and excellent antitumor effectiveness of PDT at 808 nm NIR light excitation,avoiding the laser irradiation-induced overheating issue.This study provides new insights for the development of highly efficient PDT nanodrugs toward precision theranostics.展开更多
Lanthanide ions-doped upconversion nanoparticles(UCNPs)have shown great potential in various biomedical applications.However,the upconversion luminescence(UCL)intensity of UCNPs in water environment tends to be quench...Lanthanide ions-doped upconversion nanoparticles(UCNPs)have shown great potential in various biomedical applications.However,the upconversion luminescence(UCL)intensity of UCNPs in water environment tends to be quenched.This quenching is typically attributed to non-radiative relaxation of the excited state.In this study,we designed a core-shellshell-shell NaYb_(0.88)Er_(0.12)F_(4)@NaY_(0.9)b_(0.1)F_(4)@NaY_(0.6)Nd_(0.3)Yb_(0.1)F_(4)@NaYF_(4)UCNPs that could be excited by both 980 nm and 808 nm laser,due to the doping of Nd^(3+)and Yb^(3+)ions.Our research not only utilized bulk spectral measurement but also employed single-particle level microscopic imaging to comprehensively investigate the impact of water molecules on UCL under 980 nm and 808 nm irradiation.Interestingly,our findings indicate that the absorption of water molecules has a significant effect on the UCL decay of UCNPs in aqueous solutions when excited by a 980 nm laser.This work offers a new perspective on the luminescence behavior of UCNPs in aquatic environments and provides valuable insights for their application and development in biomedicine.展开更多
Upconversion nanoparticles(UCNPs)have attracted considerable interest due to their large anti-Stokes shift,offering promising applications in lasing.Here,multi-wavelength upconversion whispering gallery mode(WGM)lasin...Upconversion nanoparticles(UCNPs)have attracted considerable interest due to their large anti-Stokes shift,offering promising applications in lasing.Here,multi-wavelength upconversion whispering gallery mode(WGM)lasing is demonstrated in silica microspheres coated with NaYF_(4)@NaYbF_(4):1%Tm^(3+)@NaYF_(4)nanoparticles and coupled with tapered fibers.Under continuous-wave 980 nm pumping,low-threshold lasing is achieved across Tm3+transitions from near-infrared to visible,with an ultra-low threshold of 0.61μWfor the 3H_(4)→3H_(6)transition.Additionally,upconversion laser output can also be achieved in Er^(3+)-and Ho^(3+)-activated microspheres.These results establish tapered fiber coupling as a versatile approach for enhancing upconversion microlasers.展开更多
基金financially supported by the National Natural Science Foundation of China(32202132,32172229)Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the Priority Academic Program Development of Jiangsu Higher Educations(PAPD)。
文摘Cadmium ion(Cd^(2+))detection technology plays a prominent role in food safety and human health.Herein,we designed and constructed an 2-aminoethyl dihydrogen phosphate(AEP)@upconversion nanoparticles(UCNPs)fluorescence sensor for quantitative detection of Cd^(2+)in paddy rice based on inner filter effect(IFE)combined with enzyme inhibition mechanism.The AEP modification UCNPs can offer a stable fluorescence donor at 658 nm and be quenched by the oxidized tetramethylbenzidine(oxTMB)catalyzed by horseradish peroxidase(HRP)enzymes.Without addition of Cd^(2+),the fluorescence of AEP@UCNPs fluorescence sensor was weaken due to the IFE between AEP@UCNPs and oxTMB.With addition of Cd^(2+),HRP enzyme activity was inhibited by Cd^(2+),leading to the decreased oxTMB,resulting in the enhance upconversion fluorescence intensity.As a result,the fluorescence intensity signal at 658 nm of the IFE-based AEP@UCNPs fluorescence sensor increased linearly with the increase in Cd^(2+)in a wide range from 0.5μmol/L to 6μmol/L and the limit of detection(LOD)was 24.6 n mol/L.In addition,our proposed IFE-based AEP@UCNPs fluorescence sensor can achieve Cd^(2+)detection in paddy rice in 30 min.
基金supported by the National Natural Science Foundation of China(Nos.21804059 and 21701059)the Natural Science Foundation of Jiangsu Province(No.BK20180974)+1 种基金the China Postdoctoral Science Foundation(No.2020M681544)the Postdoctoral Science Foundation of Jiangsu Province(No.2020Z351)。
文摘As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.
文摘目的:构建基于上转换光学成像/磁共振成像(UCL/MRI)的纳米材料UCNP-PEG-Trastuzumab,探讨其用于HER2高表达人乳腺癌细胞SKBR3的多模态显像研究。方法:采用课题组前期制备稀土掺杂钆的上转换纳米粒子(UCNP)与HER2受体特异结合的抗体曲妥单抗(Trastuzumab)的偶联获得UCL/MRI靶向探针。以高表达HER2受体的人乳腺癌细胞SKBR3细胞为观察对象,通过噻唑蓝比色法(MTT)进行细胞毒性检测。加入靶向探针UCNP-PEG-Trastuzumab共同孵育作为实验组,细胞加入UCNP-PEG共同孵育作为对照组,不添加任何探针的细胞作为空白组,利用共聚焦显微镜和MRI进行体外细胞成像;进行视觉分析与比较各组细胞光学和MRI信号,检测其结合效率。结果:1透射电子显微镜下(TEM),UCNP呈球形颗粒状,粒径约60nm;在980nm波长光激发下,发出绿色的荧光;2体外毒性试验MTT结果表明UCNP-PEG对SKBR3细胞毒性较小;320μg/m l浓度的UC N P-PEG-Tr a st u z u m ab与SK BR 3细胞孵育30分钟后,UCL/M R I成像结果均显示UC N P-PEGTrastuzumab能与SKBR3细胞靶向性结合。结论:构建HER2受体靶向特异性探针UCNP-PEG-Trastuzumab,能在体外与目的细胞特异性结合。
基金funded by the Jiangxi Province Key Laboratory of Precision Cell Therapy(No.2024SSY06241 to J.L.)the National Natural Science Foundation of China(No.82360174 to J.L.)+3 种基金the Science and Technology Department Project of Jiangxi Province(No.20224ABC03A02 to J.L.)the Key Research and Development Program of Jiangxi Province(No.20212BBG73004 to X.L.W.)the Jiangxi Province Key Laboratory of Bioengineering Drugs(No.2024SSY07061 to X.L.W.)the Graduate Innovation Special Fund Project of Jiangxi Province(No.YC2023-B046 to L.B.L.).
文摘Ultraviolet(UV)phototherapy stands as a pivotal clinical approach for managing diverse skin diseases.However,its application is constrained by concerns over UV-induced toxicity and imprecise photosensitizer delivery.This work introduces a light-converting microneedle patch(EU-MN),exemplified by its remarkable efficacy in psoriasis treatment.The EU-MN patch could release upconversion nanoparticles(UCNPs)and the photosensitizer methoxypsoralen(MOP)in controlled amounts in response to elevated matrix metalloproteinase(MMP)levels within the skin.Under near-infrared(NIR)excitation,UCNPs emit UV light(345/361 nm),which is combined with MOP to achieve more precise intradermal UV photoche-motherapy,effectively inhibiting abnormal proliferation of human immortalized epidermal cells(HaCaT)and bacterial growth(Staphylococcus aureus and Escherichia coli).Comet assay highlights DNA damage correlation.In addition,the microneedles,designed with a reactive oxygen species(ROS)-responsive shell,release epigallocatechin gallate(EGCG)to counteract excessive inflammation and mitigate UV-induced damage.In psoriasis mice,the EU-MN patch demonstrates significant therapeutic efficacy and recurrence prevention.As further evidenced by the suppression of epidermal hyperplasia and inflammation(through RNA sequencing identifying cell cycle arrest),this EU-MN patch offers a safer,more precise,and more effective alternative strategy for conventional direct UV phototherapy.
基金This work was financially supported by National Natural Science Foundation of China(NSFC,Nos.21601140 and 21871214)the Fundamental Research Funds for the Central Universities,and Open Research Fund of State Key Laboratory of Bioelectronics.
文摘The nanoplatforms based on upconversion nanoparticles(UCNPs)have shown great promise in amplified photodynamic therapy(PDT)triggered by near-infrared(NIR)light.However,their practical in vivo applications are hindered by the overheating effect of 980 nm excitation and low utilization of upconversion luminescence(UCL)by photosensitizers.To solve these defects,core-satellite metal-organic framework@UCNP superstructures,composed of a single metal-organic framework(MOF)NP as the core and Nd3+-sensitized UCNPs as the satellites,are designed and synthesized via a facile electrostatic self-assembly strategy.The superstructures realize a high co-loading capacity of chlorin e6(Ce6)and rose bengal(RB)benefitted from the highly porous nature of MOF NPs,showing a strong spectral overlap between maximum absorption of photosensitizers and emission of UCNPs.The in vitro and in vivo experiments demonstrate that the dual-photosensitizer superstructures have trimodal(magnetic resonance(MR)/UCL/fluorescence(FL))imaging functions and excellent antitumor effectiveness of PDT at 808 nm NIR light excitation,avoiding the laser irradiation-induced overheating issue.This study provides new insights for the development of highly efficient PDT nanodrugs toward precision theranostics.
基金financially suppor ted by the National Key Research and Development Program of China(2022YFB3503700)the National Natural Science Foundation of China(22074021)
文摘Lanthanide ions-doped upconversion nanoparticles(UCNPs)have shown great potential in various biomedical applications.However,the upconversion luminescence(UCL)intensity of UCNPs in water environment tends to be quenched.This quenching is typically attributed to non-radiative relaxation of the excited state.In this study,we designed a core-shellshell-shell NaYb_(0.88)Er_(0.12)F_(4)@NaY_(0.9)b_(0.1)F_(4)@NaY_(0.6)Nd_(0.3)Yb_(0.1)F_(4)@NaYF_(4)UCNPs that could be excited by both 980 nm and 808 nm laser,due to the doping of Nd^(3+)and Yb^(3+)ions.Our research not only utilized bulk spectral measurement but also employed single-particle level microscopic imaging to comprehensively investigate the impact of water molecules on UCL under 980 nm and 808 nm irradiation.Interestingly,our findings indicate that the absorption of water molecules has a significant effect on the UCL decay of UCNPs in aqueous solutions when excited by a 980 nm laser.This work offers a new perspective on the luminescence behavior of UCNPs in aquatic environments and provides valuable insights for their application and development in biomedicine.
基金National Natural Science Foundation of China(62122027,62075063,62205109,62405092,52202004)Postdoctoral Fellowship Program of CPSF(GZC20230852)+1 种基金State Key Laboratory of Luminescent Materials and Devices(Skllmd-2024-12)China Scholarship Council Grant(202406150002)。
文摘Upconversion nanoparticles(UCNPs)have attracted considerable interest due to their large anti-Stokes shift,offering promising applications in lasing.Here,multi-wavelength upconversion whispering gallery mode(WGM)lasing is demonstrated in silica microspheres coated with NaYF_(4)@NaYbF_(4):1%Tm^(3+)@NaYF_(4)nanoparticles and coupled with tapered fibers.Under continuous-wave 980 nm pumping,low-threshold lasing is achieved across Tm3+transitions from near-infrared to visible,with an ultra-low threshold of 0.61μWfor the 3H_(4)→3H_(6)transition.Additionally,upconversion laser output can also be achieved in Er^(3+)-and Ho^(3+)-activated microspheres.These results establish tapered fiber coupling as a versatile approach for enhancing upconversion microlasers.
