Aptamer-based Membrane Protein Analysis and Molecular Diagnostics

Membrane proteins are vital components of the cell membrane and play crucial roles in various cellular activities.Analysis of membrane proteins is of paramount importance for studying molecular events inside cells and organisms and holds promising prospects for early disease diagnosis and treatment assessment.Benefiting from obvious merits including high affinity,high specificity and ease of modification,aptamers have been regarded as ideal molecular recognition elements in membrane protein analysis and molecular diagnostics strategies.This review summarised recent advances in membrane protein-specific aptamer screening,aptamer-based static and dynamic membrane protein analysis,and aptamer-based molecular diagnostic techniques.Prospects and challenges were also discussed.

Molecular imaging:design mechanism and bioapplications

Molecular imaging is a non-invasive method to image and analyze the concentration and activity of functional biomolecules in cells or in vivo at molecular level,and plays an increasing role in deep understanding of biological processes,early and accurate diagnosis of diseases,and evaluation of treatment.Nowadays,numerous novel molecular imaging probes have been developed,involving every biomedical imaging modality,such as optical imaging,photoacoustic imaging,magnetic resonance imaging,single-photon-emission computed tomography,and positron emission tomography.In this review,we summarize the development of current state-of-the-art molecular imaging probes.We introduce the design strategies of molecular probes and detailed imaging modalities,and highlight the properties of probes and biomedical imaging applications in cells and in vivo,including disease diagnosis,drug tracking,and imaging-guided surgery.Then we discuss the perspectives and challenges in this emerging field.We expect this review could inspire more effective molecular imaging probes to be developed,achieving the goal towards clinical practices.

Ultrastable graphene isolated Au Ag nanoalloy for SERS biosensing and photothermal therapy of bacterial infection

Plasmonic metal nanomaterials with intrinsic surface–enhanced Raman scattering(SERS)and photothermal properties,especially AuAg nanoalloys with both the outstanding merits of Au and Ag nanocrystals,show huge application prospects in bacterial theranostics.However,the direct exposure of AuAg nanoalloys in external conditions probably cause undesirable reactions and poisonous metal ion leakage during SERS detection and photothermal antibacterial therapy process,which severely hinder bacterial theranostics applications.Herein,we report an ultrastable graphene–isolated AuAg nanoalloy(GAA)with AuAg core confined in few–layer graphitic shell as a versatile platform for bacterial detection and therapy.The encapsulation of graphene ensures the good stability of AuAg core,that its superior SERS and photothermal properties are therefore further guaranteed.GAA is used for SERS detection of two vital bacterial biomarkers(including corrosive cyanide and pyocyanin),exhibiting good SERS quantitative and multiplexing ability.GAA is further used for photothermal antibacterial therapy application,and ultrahigh antibacterial efficacies for both Gram–negative Escherichia coli and Gram–positive Staphylococcus aureus are achieved under 808 nm laser irradiation.This work proposes a valuable method to develop robust bacterial theranostic platform.

Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle

Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.

Current Advances in Aptamer-based Biomolecular Recognition and Biological Process Regulation

The interaction between biomolecules with their target ligands plays a great role in regulating biological functions.Aptamers are short oligonucleotide sequences that can specifically recognize target biomolecules via structural complementarity and thus regulate related biological functions.In the past ten years,aptamers have made great progress in target biomolecule recognition,becoming a powerful tool to regulate biological functions.At present,there are many reviews on aptamers applied in biomolecular recognition,but few reviews pay attention to aptamer-based regulation of biological functions.Here,we summarize the approaches to enhancing aptamer affinity and the advancements of aptamers in regulating enzymatic activity,cellular immunity and cellular behaviors.Furthermore,this review discusses the challenges and future perspectives of aptamers in target recognition and biological functions regulation,aiming to provide some promising ideas for future regulation of biomolecular functions in a complex biological environment.

Molecularly Engineered Aptamers Targeting Tumor Tissue and Cancer Cells for Efficient in Vivo Recognition and Enrichment

Molecular engineering of aptamers can confer exogenous biomedical properties that may be beneficial for various applications.In this study,a tumor-homing peptide modification strategy was developed to considerably enhance the accumulation and penetration abilities of the Sgc8c aptamer.Notably,the S2PM conjugate induced a much higher level of morphological variation in three-dimensional tumor microspheres(HCT116 cells)than in control groups,highlighting the importance of the homing and penetrating abilities derived from peptide.

New Insights from Chemical Biology:Molecular Basis of Transmission,Diagnosis,and Therapy of SARS-CoV-2

Coronavirus disease 2019(COVID-19)is caused by a novel strain of coronavirus,designated as severe acute respiratory syndrome coronavirus 2(SARSCoV-2).It has caused a global pandemic rapidly sweeping across all countries,bringing social and economic hardship to millions.Most countries have implemented early warning measures to detect,isolate,and treat patients infected with SARS-CoV-2.This minireview summarizes some of those steps,in particular,testing methods and drug development in the context of chemical biology,and discusses the molecular basis of COVID-19’s virulent transmissibility.

Preparation,applications,and challenges of functional DNA nanomaterials

As a carrier of genetic information,DNA is a versatile module for fabricating nanostructures and nanodevices.Functional molecules could be integrated into DNA by precise base complementary pairing,greatly expanding the functions of DNA nanomaterials.These functions endow DNA nanomaterials with great potential in the application of biomedical field.In recent years,functional DNA nanomaterials have been rapidly investigated and perfected.There have been reviews that classified DNA nanomaterials from the perspective of functions,while this review primarily focuses on the preparation methods of functional DNA nanomaterials.This review comprehensively introduces the preparation methods of DNA nanomaterials with functions such as molecular recognition,nanozyme catalysis,drug delivery,and biomedical material templates.Then,the latest application progress of functional DNA nanomaterials is systematically reviewed.Finally,current challenges and future prospects for functional DNA nanomaterials are discussed.

Interfacial Polymer Engineered Field Effect Transistor Biosensors for Rapid and Efficient Identification of SARS-CoV-2 N Antigen

With the advantages of high sensitivity,rapid response,label-free,and simple operation,field effect transistor biosensors have shown promising application prospects in large-scale pathogen screening.However,in practical biological fluids with relatively high ionic strength,such as saliva and serum,the Debye screening effect will weaken the interaction between FET biosensors and target bio-molecules,thereby affecting the sensing sensitivity and accuracy.

Versatile Graphene-Isolated AuAg-Nanocrystal for Multiphase Analysis and Multimodal Cellular Raman Imaging

Surface-enhanced Raman spectroscopy(SERS)-based bioanalytical technique involves the interaction of SERS-active substrate with complex environment,which has aroused intensive research interests.Compared to the commonly used Au SERS substrates,Ag nanocrystals have larger optical absorption cross section and acceptable price,but they possess poor oxidation resistance and potential biotoxicity,and the occurrence of unnecessary chemical reactions is inevitable due to the direct contact with probe molecules.Herein,we report a graphene-isolated AuAg nanocrystal(GIAAN)with the SERS-active AuAg core confined in a nanospace of few-layer graphene shell,which possesses unique Raman peaks,high SERS activity,excellent stability,superior fluorescence quenching performance and good biocompatibility.Based on the limited solubility of GIAAN in water and organic solvents,it is able to spontaneously generate interfacial self-assembled GIAAN(ISA-GIAAN)film at immiscible two-phase interfaces without any inducer,and multiphase Raman analysis of both water-and lipid-soluble drug model molecules is further achieved.Moreover,the GIAAN is further non-covalently functionalized with polyoxyethylenestearyl ether(C18-PEG)to acquire GIAAN@PEG with good water-solubility for SERS quantitative analysis in homogeneous system and multimodal Raman imaging of MCF-7 cells.We expect the versatile GIAAN holds great potential to monitor drug metabolism and guide intended drug delivery in clinic trials.

Functional nucleic acid-based cell imaging and manipulation

Cells are the basic structural and functional units of organisms.Dynamic analysis and manipulation of specific components in living cells would provide valuable information for the study of related biological processes.Advances in fluorescence microscopy have allowed real-time monitoring of biological events at the molecular level.Meanwhile,the development of highperformance fluorescence probes has become a critical issue.Functional nucleic acids(FNAs)are oligonucleotides with special chemical and biological functions,and aptamers with excellent molecular recognition capability are one of the most important representatives.They have attracted extensive attention in the field of live-cell study,owing to intrinsic advantages of simple synthesis,convenient modification,low immunogenicity and high programmability.This review focuses on recent research progress in fluorescence imaging and manipulation of cells using FNAs,particularly aptamers,as the molecular tools.Finally,a summary is provided and the related challenges are discussed.

A Magnetocatalytic Propelled Cobalt-Platinum@Graphene Navigator for Enhanced Tumor Penetration and Theranostics

Complex biological environments and multiple physiological barriers significantly impede efficient accumulation and penetration of nanomaterials within tumor tissue for therapy.In situ energy conversion of nanomotors features autonomous movements and improves cancer treatment.However,one of the key challenges is to prepare nanomotors with an adequately small size,good biocompatibility,and precise positioning.Herein,we demonstrate a simple,ultrasmall,versatile,and real-time motion guidance strategy for magnetocatalytic CoPt@graphene navigators(MCGNs)that can enable highly efficient propulsion in the presence of H_(2)O_(2) or magnetic actuation.MCGNs act as highly diffusive delivery vehicles to promote tumor tissue targeting,and the amount of drug in the tumor was three times than without navigation.By engaging movements powered through in situ energy conversion,MCGNs gain considerable propulsion to penetrate a cell’s membrane and enhance intracellular delivery.

Activatable and Self-Monitoring Hydrogen Sulfide-Based Molecular Senomorphics for Visualized Regulation of Cellular Senescence

Specific regulation of the senescence-associated secretory phenotype(SASP)is vital to block senescence-induced detrimental cellular plasticity.Recently,some chemical compounds called senomorphics have demonstrated such potential,but it remains challenging to achieve site-specific activation and real-time monitoring of the action of senomorphics,posing great obstacles for transformable applications.Here,we report a tailor-made hydrogen sulfide(H_(2)S)donor(Lyso-FH_(2)S-Gal)as a new class of molecule senomorphics for spatially controlled delivery of H_(2)S for visualization of regulation of cellular senescence.It comprises four functional moieties in a single molecular structure,including a lysosome-targeting group for cell recognition,a lysosomal enzyme-cleaved scaffold for site-specific activation,thiocarbamate as the H_(2)S precursor,and a switchable fluorophore for concurrent selfreporting of H_(2)S release and senescence imaging.Lyso-FH_(2)S-Gal exhibited remarkable response selectivity,sustained H_(2)S release,and 141-fold fluorescence enhancement.In cellular models,Lyso-FH_(2) S-Gal preferentially enriched in senescent cells over nonsenescent cells,and alleviated the levels of SASP and reactive oxygen species(ROS)in senescent cells,while remaining inert in nonsenescent cells.More impressively,it efficiently inhibited the SASPmediated crosstalk between senescent cells and surrounding nonsenescent cells,thereby preventing senescence propagation.This work offers a useful molecular tool with the hope for controlled intervention of senescence-related important biological processes.

Electron transfer in protein modifications:from detection to imaging

Signal pathways participate in vital biological processes and regulate complex life activities through protein modifications.Protein modifications in signal pathways are accompanied by electron transfer.The study of electronic behavior helps to explore the physical and chemical processes in signal pathways,receiving extensive attention.There are some excellent reviews that have summarized methods for signal pathway detection,while few discussions are from an electron transfer perspective.This review describes the relationship between signal pathways and electron transfer in protein modification.Subsequently,we summarize the electron transfer-based detection methods,such as electrochemical,photoelectrochemical and electrochemiluminescence methods.Additionally,the applications of signal pathway detection in mechanism study and imaging are also reviewed.Finally,a comprehensive discussion of the summary and outlooks in this field is presented,aiming to provide valuable guidance for the molecular mechanism of life processes and the development of new analytical techniques.

Recent progress of aptamer-drug conjugates in cancer therapy

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures.Compared to antibody-drug conjugates(ADC),aptamer-drug conjugate(ApDC)is also an efficient,targeted drug for cancer therapy with a smaller size,higher chemical stability,lower immunogenicity,faster tissue penetration,and facile engineering.Despite all these advantages,several key factors have delayed the clinical translation of ApDC,such as in vivo off-target effects and potential safety issues.In this review,we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Real-Time Monitoring of Dynamic Chemical Processes in Microbial Metabolism with Optical Sensors

Monitoring microbial metabolism is vital for revealing the mechanism of disease related to microbial metabolism and providing guidance for biomanufacturing processes optimization.However,it remains a grand challenge to offer real-time insights into microbial metabolism owing to the complex and dynamic process.In this paper,the recent advances and prospects of optical biosensors including the organic,genetic coding and inorganic optical biosensors are briefly described for real-time monitoring of dynamic microbial metabolism.This paper points out that challenges remain in microbial heterogeneity.We believe that this work will inspire the application of developing new methods for single cell real-time analysis.

Room-Temperature Persistent Luminescence in Metal Halide Perovskite Nanocrystals for Solar-Driven CO_(2)Bioreduction

The rapid crystal growth of metal halide perovskite(MHP)nanocrystals inevitably leads to the generation of abundant crystal defects in the lattice.Here,defects-mediated long-lived charges and accompanying room-temperature persistent luminescence are demonstrated to be a general phenomenon in MHP nanocrystals.Density functional theory calculations suggest that the collaboration of Schottky and point defects enables upward cascading depletion for electron transfer in MHP nanocrystals,leading to the generation of long-lived photoexcited charges with lifetimes over 30 min.The excellent optical properties including the presence of long-lived charges,high charge separation efficiency,and broad absorption in the visible region make MHPs ideal candidates for both photocatalysis and photobiocatalysis.The MHPs were further integrated with enzymes to construct a light-driven biosynthetic system for the selective production of fine chemicals from CO_(2)with solar energy.The biosynthetic system can produce formate with a quantum yield of 3.24%,much higher than that of plants(∼0.2-1.6%).These findings will benefit the understanding of the optoelectronic properties of MHPs and further provide opportunities for the development of biosynthetic systems for solar-to-chemical synthesis.

Recent progress in synthesis of lanthanide-based persistent luminescence nanoparticles

Persistent luminescence nanoparticles(PLNPs)are a kind of phosphors that can remain luminescent for seconds to several days after the stoppage of excitation.Lanthanides show the special capability to largely broaden the emission range and enhance the luminescence intensity of PLNPs due to their dense energy structure and unique electronic configurations.In the past decades,various methods have been developed for the synthesis of lanthanide-based PLNPs with excellent pe rsistent luminescence propertie s,and the lanthanide-based PLNPs are widely studied in areas including biome dicine,energy,and information storage.In this review,we summarized the research progress in the synthe sis of lanthanidebased PLNPs and outline d several typical synthesis methods.We discussed the fundamental concepts of preparation methods as well as the advantages and drawbacks of the typical synthetic approache s.Moreove r,the current challenges and the potential solutions for the development of lanthanide-based PLNP s are also discussed in an attempt to provide strate gies to further improve the optical properties of lanthanide-based PLNPs.We hope this review can contribute to the design of lanthanide-based PLNPs with desired properties and further promote their applications in biomedicine,energy,and information science.

Versatile metal graphitic nanocapsules for SERS bioanalysis

The novel graphitic nanomaterial of metal graphitic nanocapsules(MGNs) with superior stability, unique optical properties and biocompatibility possess great potential in biomedical and bioanalytical applications. The graphitic shell can quench the background fluorescence interference from external environments via a fluorescence resonance energy transfer(FRET) process and even avoid unnecessary reactions catalyzed by inner metal core. The graphitic shell with several characteristic Raman bands itself can act as Raman signal probe or internal standard(IS), especially the 2D-band within the cellular Raman-silent region helps to reduce the interference signals from external conditions. The present context attempts to give a comprehensive overview about the preparation and unique properties of MGNs as well as their applications in SERS biodetection and bioimaging.