Simultaneous and quantitative detection of multiple exosomal micro RNAs(miRNAs)was successfully performed by a surface-enhanced Raman scattering(SERS)assay consisting of Raman probes and capture probes.In this design,...Simultaneous and quantitative detection of multiple exosomal micro RNAs(miRNAs)was successfully performed by a surface-enhanced Raman scattering(SERS)assay consisting of Raman probes and capture probes.In this design,the asymmetric core-shell structured Au@Au@Ag nanoparticles were first synthesized by layer-by-layer self-assembly method and modified with different Raman molecules and recognition sequences(poly A-DNA)to prepare the surface-enhanced Raman probes.Then,the streptavidinmodified magnetic beads were used to immobilize the biotinylated DNA capture sequences(biotin-DNA)to obtain capture probes.In the presence of target exosomal miRNAs,the Raman probes and capture probes could bind to the target exosomal miRNAs in the partial hybridization manner.Thus,the developed SERS sensor could indicate the target miRNAs levels in the buffer solution.Using breast cancerrelated miRNAs as model targets,the limits of detection of this sensor were determined to be 1.076 fmol/L for synthetic miR-21,0.068 fmol/L for synthetic miR-126,and 4.57 fmol/L for synthetic miR-1246,respectively.Such SERS sensors were further employed to detect the miR-21 in 20%human serum and the extraction solution of exosomes,respectively.Therefore,simultaneous and multiplex detection of cancerrelated exosomal miRNAs by this assay could provide new opportunities for further biomedical applications.展开更多
Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displ...Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displacement(TMSD)and branch migration.With their sensitive and efficient signal amplification capabilities,NDARs have become essential tools for biomarker detection and intracellular imaging.They encompass four primary amplification methods:catalytic hairpin assembly(CHA),hybridization chain reaction(HCR),DNAzyme-based amplification,and entropy-driven circuits(EDC).Based on amplification mechanisms,NDARs can be categorized into three types:stimuli-responsive NDARs,which employ single amplification strategies triggered by specific stimuli like pH,light,or biomolecules;cascade NDARs,which integrate two or more amplification reactions for stepwise signal enhancement;and autocatalytic NDARs,which achieve exponential amplification through self-sustained cycling.These advanced designs progressively improve amplification efficiency,enhance sensitivity,and minimize background noise,enabling precise detection of proteins,viruses,and nucleic acids as well as applications in cancer cell imaging and therapy.Compared with classical NDARs,these approaches significantly reduce signal leakage,offering broader applicability in diagnostics,imaging,and therapeutic contexts.This review summarizes recent advancements,addresses existing challenges,and explores future directions,providing insights into the development and applications of NDARs.展开更多
A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK...A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.展开更多
基金the Project of National Natural Science Foundation of China(Nos.21775036,21735002,21874035 and 22174044)。
文摘Simultaneous and quantitative detection of multiple exosomal micro RNAs(miRNAs)was successfully performed by a surface-enhanced Raman scattering(SERS)assay consisting of Raman probes and capture probes.In this design,the asymmetric core-shell structured Au@Au@Ag nanoparticles were first synthesized by layer-by-layer self-assembly method and modified with different Raman molecules and recognition sequences(poly A-DNA)to prepare the surface-enhanced Raman probes.Then,the streptavidinmodified magnetic beads were used to immobilize the biotinylated DNA capture sequences(biotin-DNA)to obtain capture probes.In the presence of target exosomal miRNAs,the Raman probes and capture probes could bind to the target exosomal miRNAs in the partial hybridization manner.Thus,the developed SERS sensor could indicate the target miRNAs levels in the buffer solution.Using breast cancerrelated miRNAs as model targets,the limits of detection of this sensor were determined to be 1.076 fmol/L for synthetic miR-21,0.068 fmol/L for synthetic miR-126,and 4.57 fmol/L for synthetic miR-1246,respectively.Such SERS sensors were further employed to detect the miR-21 in 20%human serum and the extraction solution of exosomes,respectively.Therefore,simultaneous and multiplex detection of cancerrelated exosomal miRNAs by this assay could provide new opportunities for further biomedical applications.
基金the financial support of the Hong Kong Research Grant Council(14300822)the Chinese University of Hong Kong(CUHK)+1 种基金The TOC figure was created with BioRender.com.the original authors of the images used in the review.
文摘Nonenzymatic nucleic acid amplification reactions,especially nonenzymatic DNA amplification reactions(NDARs),are thermodynamically driven processes that operate without enzymes,relying on toehold-mediated strand displacement(TMSD)and branch migration.With their sensitive and efficient signal amplification capabilities,NDARs have become essential tools for biomarker detection and intracellular imaging.They encompass four primary amplification methods:catalytic hairpin assembly(CHA),hybridization chain reaction(HCR),DNAzyme-based amplification,and entropy-driven circuits(EDC).Based on amplification mechanisms,NDARs can be categorized into three types:stimuli-responsive NDARs,which employ single amplification strategies triggered by specific stimuli like pH,light,or biomolecules;cascade NDARs,which integrate two or more amplification reactions for stepwise signal enhancement;and autocatalytic NDARs,which achieve exponential amplification through self-sustained cycling.These advanced designs progressively improve amplification efficiency,enhance sensitivity,and minimize background noise,enabling precise detection of proteins,viruses,and nucleic acids as well as applications in cancer cell imaging and therapy.Compared with classical NDARs,these approaches significantly reduce signal leakage,offering broader applicability in diagnostics,imaging,and therapeutic contexts.This review summarizes recent advancements,addresses existing challenges,and explores future directions,providing insights into the development and applications of NDARs.
基金funded by Hong Kong Research Grant Council(GRF14300822)Faculty of Science of the Chinese University of Hong Kong(CRIMS)+1 种基金the Natural Science Foundation of Shandong Province(ZR2023MC178)Youth Innovation Team Development Project of Shandong Province(Food Nanotechnology innovation team).
文摘A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.
