Efficient production of ligand-free microscintillators at gram-scale for high-resolution X-ray luminescence imaging

The efficient production of high-quality scintillators with long radioluminescence afterglow is crucial for high-performance X-ray luminescence extension imaging.However,scaling-up the synthesis of ligand-free scintillators to fabricate large-area X-ray imaging screens for industrial applications remains a challenge.In this study,we report an efficient method to synthesize ligand-free,lanthanide-doped microscintillators by a one-pot reaction via the concentrated hydrothermal method.The as-synthesized microscintillators exhibit prolonged persistent radioluminescence for up to 30 days after X-ray exposure and remain high stability in air or water for more than 18 months without deterioration.Monte Carlo simulations indicate that the size effect is responsible for the excellent afterglow performance of the microscintillators.We employ these high-quality lanthanide-doped microscintillators to fabricate a large-area X-ray imaging detector using a blade-coating method,a spatial resolution of 24.9 lp/mm for X-ray imaging.Our study offers a solution for scaling-up the synthesis of low-cost microscintillators for practical applications.

A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings

In recent years,the developed hemostatic technologies are still difficult to be applied to the hemostasis of massive arterial and visceral hemorrhage,owing to their weak hemostatic function,inferior wet tissue adhesion,and low mechanical properties.Herein,a mussel-inspired supramolecular interaction-cross-linked hydrogel with robust mechanical property(308.47±29.20 kPa)and excellent hemostatic efficiency(96.5%±2.1%)was constructed as a hemostatic sealant.Typically,we combined chitosan(CS)with silk fibroin(SF)by cross-linking them through tannic acid(TA)to maintain the structural stability of the hydrogel,especially for wet tissue adhesion ability(shear adhesive strength=29.66±0.36 kPa).Compared with other materials reported previously,the obtained CS/TA/SF hydrogel yielded a lower amount of blood loss and shorter time to hemostasis in various arterial and visceral bleeding models,which could be ascribed to the synergistic effect of wound closure under wet state as well as intrinsic hemostatic activity of CS.As a superior hemostatic sealant,the unique hydrogel proposed in this work can be exploited to offer significant advantages in the acute wound and massive hemorrhage with the restrictive access of therapeutic moieties.

Efficient and Fast X-Ray Luminescence in Organic Phosphors Through High-Level Triplet-Singlet Reverse Intersystem Crossing

Organic scintillators that efficiently generate bright triplet excitons are of critical importance for highperformance X-ray-excited luminescence in radiation detection.However,the nature of triplet-singlet spinforbidden transitions in these materials often result in long-lived phosphorescence,which is undesirable for ultrafast X-ray detection and imaging.Here we demonstrate that the effect of hybridized local and charge-transfer(HLCT)excited states enables organic scintillators to exhibit highly efficient and fast radioluminescence(RL)in response to X-ray irradiation.Our experimental and theoretical investigation shows that the oxidized 1,8-naphthalimide-phenothiazine dyad(OMNI-PTZ 2)with HLCT-excited states has an enhanced overlap integral of the highest occupied molecular orbital(HOMO)and lowest unoccupied molecular orbital(LUMO)on MNIπ-orbitals,and moderate donor–acceptor electron interactions.As a result,the RL of these crystals exhibits a 61-fold increase and its monoexponential decay lifetime is three orders of magnitude faster compared to its corresponding thermally activated delayed fluorescence(TADF)molecule MNI-PTZ 1.We further demonstrate the practical utility of the OMNI-PTZ 2(G)in high-performance X-ray detection and imaging,achieving an X-ray dose sensitivity of 97 nGy s−1 and an exceptional spatial resolution of 20 lp/mm.Our study provides a promising molecular design principle for utilizing triplet excitons to develop high-efficiency and fast X-ray scintillators for the development of next-generation flexible and stretchable X-ray imaging detectors.

Dual inhibition of glycolysis and oxidative phosphorylation by aptamer-based artificial enzyme for synergistic cancer therapy

Dual inhibition of glycolysis and oxidative phosphorylation(OXPHOS)can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy.However,the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution.Herein,we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS,which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride(AptCCN).AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine,and further catalyze the oxidation of enriched arginine to nitric oxide(NO)under red light irradiation.In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS,leading to energy blockage and apoptosis of cancer cells.The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.

Miniaturized electrochemical sensors and their point-of-care applications

Most of the current analytical methods depend largely on laboratory-based analytical techniques that require expensive and bullky equipment,potentially incur costly testing,and involve lengthy detection processes.With increasing requirements for point-of-care testing(POCT),more attention has been paid to miniaturized analytical devices.Miniaturized electrochemical(MEC)sensors,including different material-based MEC sensors(such as DNA-,paper-,and screen electrode-based),have been in strong demand in analytical science due to their easy operation,portability,high sensitivity,as well as their short analysis time.They have been applied for the detection of trace amounts of target through measuring changes in electrochemical signal,such as current,voltage,potential,or impedance,due to the oxidation/reduction of chemical/biological molecules with the help of electrodes and electrochemical units.MEC sensors present great potential for the detection of targets including small organic molecules,metal ions,and biomolecules.In recent years,MEC sensors have been broadly applied to POCT in various fields,including health care,food safety,and environmental monitoring,owing to the excellent advantages of electrochemical(EC)technologies.This review summarized the state-of-the-art advancements on various types of MEC sensors and their applications in POCT.Furthermore,the future perspectives,opportunities,and challenges in this field are also discussed.

Ultrasound-propelled Janus Au NR-mSiO_(2) nanomotor for NIR-II photoacoustic imaging guided sonodynamic-gas therapy of large tumors

Varieties of contrast agents have been developed for photoacoustic(PA)and ultrasound(US)imaging of cancers in vivo.However,access of traditional contrast agents into the sites of tumors has been principally through passive infiltration without any external force,preventing their deep penetration into the tissues of the tumors,and hindering the use of PA and US for deep tumor imaging.The concept of micro/nanomotors has been the focus of increasing attention as active theranostic agents due to their active movement in particular fluids,thereby conducting assigned tasks.Herein,US-propelled Janus mesoporous SiO_(2)partially coated gold nanorods(Au NR-mSiO_(2))were fabricated for deep tumor NIR-II PA imaging and synergistic sonodynamic-gas therapy.Following US irradiation,2,2-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AIPH)loaded in mSiO_(2)(Au NR-mSiO_(2)/AIPH)generated N_(2)microbubbles with high efficiency to achieve nanomotor drive.Due to the deep penetration of US,the nanomotors exhibited a capability to travel deep within sites of tumors,providing enhanced PA/US imaging inside the tumors.Furthermore,the nanomotor based cancer therapy was demonstrated through synergistic N_(2)gas and sonodynamic therapy.The US-propelled nanomotors demonstrated a novel strategy for the simultaneous PA/US dual imaging deep within tumor tissues and precise therapy of large tumors.

An Activatable Near-Infrared Molecular Chemiluminescence Probe for Visualization of NQO1 Activity In Vivo

Chemiluminescence(CL)is a promising tool for diagnostics and sensing due to its inherent excitation light-free.However,most CL probes emit exclusively visible light with limited penetration depth,hindering their broad application for in vivo deep tissue imaging.This work reports an activated unimolecular CL probe(CL-P)that emits light in the near-infrared(NIR)region allowing a superior real-time visualization and detection of NAD(P)H quinone oxidoreductase 1(NQO1)in vivo.The NQO1-specific trimethyl-locked quinone is a lock for masking the NQO1 trigger site,and it was conjugated on the NIR Schaap's dioxetane chemiluminophore,achieving not only a subtle signal-to-noise ratio even at a depth of 15 mm in the chicken breast tissues,but also sensitively detecting the positive expression of NQO1 in A549 cells.CL-P has been successfully used for visualizing the aberrantly expressed NQO1 in subcutaneous xenograft A549 tumors.To our knowledge,this is the first work reporting the detection of NQO1 activity in the NIR region by unimolecular CL mode.Overall,the NQO1-activated visualization platform provides a guideline to transform a unimolecular CL sensor into a licensed imaging agent for the in vivo detection of enzyme-related diseases.

A Bright Nitrogen-doped-Carbon-Dots based Fluorescent Biosensor for Selective Detection of Copper Ions

In this work,a novel fluorescent biosensor has been constructed for rapid detection of Cu(Ⅱ)via the interaction between the fluorophore groups on the surface of nitrogen-doped-carbon-dots(N-CDs)and·OH produced from the catalytic reaction between Cu(Ⅱ)and cysteine(Cys).Specifically,Cu(Ⅱ)can catalyze the oxidation of Cys to form cystine(Cys–Cys)and hydrogen peroxide(H_(2)O_(2)),and Cu(Ⅱ)can also catalyze the decomposition of H_(2)O_(2)to produce hydroxyl radicals(·OH)by the Fenton-like reaction.·OH can oxidize and destroy the surface structure of N-CDs,resulting in the fluorescence quenching of the N-CDs.Under the optimal experimental conditions,the linear range of Cu(Ⅱ)is determined to be 0.05–25μmol L_(-1,),and the limit of detection is 23 nmol L^(-1)with the limit of quantitation of 77 nmol L^(-1).Besides,some characterizations are provided to verify the proposed principle.The method has been successfully applied for the detection of Cu(Ⅱ)in human serum and environmental water with high sensitivity and higher selectivity.

Emerging NIR-Ⅱ Luminescent Gold Nanoclusters for In Vivo Bioimaging

Gold nanoclusters(AuNCs)with near-infraredⅡ(NIR-Ⅱ)photoluminescence(PL)have emerged as novel bioimaging probes for in vivo disease diagnosis.So far,it still lacks a systematic review focusing on the synthesis,PL tuning,and in vivo imaging of NIR-Ⅱluminescent AuNCs.In this review,we briefly introduce the synthesis of NIR-Ⅱluminescent AuNCs using various surface ligands.We discuss the origins and properties of NIR-ⅡPL in AuNCs,and summarize the strategies for improving and/or tuning NIR-ⅡPL emissions.We also provide an overview of the recent progress in the application of AuNCs in tumor-targeted imaging,molecular imaging,and other areas(such as the sensitive imaging of bones,vessels,lymph nodes,etc.).Finally,we present the prospects and challenges in the field of NIR-Ⅱluminescent AuNCs and related imaging applications,expecting to offer comprehensive understanding of this field,and thereby deepening and broadening the biological application of AuNCs.

X-ray sensitive high-Z metal nanocrystals for cancer imaging and therapy

Radiotherapy(RT)based on X-ray irradiation is a widely applied cancer treatment strategy in the clinic.However,treating cancer based on RT alone usually results in insufficient radiation energy deposition,which inevitably has serious side effects on healthy parts of the body.Interestingly,high atomic number(high-Z)metal nanocrystals as X-ray sensitizers can reduce the radiation dose effectively due to their high X-ray absorption,which has attracted increased attention in recent years.High-Z metal nanocrystals produce Auger and photoelectrons electrons under X-ray irradiation,which could generate large amounts of reactive oxygen species,and induce cellular damages.The sensitization effect of high-Z metal nanocrystals is closely related with their composition,morphologies,and size,which would strongly impact their performances in the application of cancer imaging and therapy.In this review,we summarize diverse types of X-ray sensitizers such as bismuth,hafnium,gold,and gadolinium for cancer RT and imaging applications.In addition,current challenges and the outlook of RT based on high-Z metal nanocrystals are also discussed.

Halogenated Thermally Activated Delayed Fluorescence Materials for Efficient Scintillation

Organic scintillators,materials with the ability to exhibit luminescence when exposed to X-rays,have aroused increasing interest in recent years.However,the enhancement of radioluminescence and improving X-ray absorption of organic scintillators lie in the inherent dilemma,due to the waste of triplet excitons and weak X-ray absorption during scintillation.Here,we employ halogenated thermally activated delayed fluorescence materials to improve the triplet exciton utilization and X-ray absorption simultaneously,generating efficient scintillation with a low detection limit,which is one order of magnitude lower than the dosage for X-ray medical diagnostics.Through experimental study and theoretical calculation,we reveal the positive role of X-ray absorption,quantum yields of prompt fluorescence,and intersystem crossing in promoting the radioluminescence intensity.This finding offers an opportunity to design diverse types of organic scintillators and expands the applications of thermally activated delayed fluorescence.

Building Block Symmetry Relegation Induces Mesopore and Abundant Open-Metal Sites in Metal-Organic Frameworks for Cancer Therapy

The judicious choice of metal clusters and organic building blocks leads to a wide variety of structures for metal–organic frameworks(MOFs).In this work,we demonstrated that relegating the symmetry of a building block can also lead to the proliferation of new MOF structures.Herein,a triangle building block was elongated with reduced symmetry for MOF construction,which gave rise to a novel(3,4,6)-connected idp(based on the definition of Reticular Chemistry Structure Resource,http://rcsr.net/)network(PFC-16)with mesopores and abundant open-metal sites.The framework is composed of the rarely observed tetrakis hexahedral cages,surrounding which are small cages arranged in sodalite topology.The relegated symmetry was required for this novel self-assembly.The obtained MOF with mesopores,a robust backbone,and abundant open-metal sites can incorporate functional species in the structure,which is representatively demonstrated by internalizing the photosensitizer zinc(II)phthalocyanine(ZnPc)and the modifying tumor-targeting molecule folic acid(FA)in PFC-16.The obtained composite FA-ZnPc@nano-PFC-16 shows excellent photodynamic therapy(PDT)efficiency for both in vitro and in vivo experiments,representing a promising candidate for cancer therapy.

Dual activated NIR-Ⅱ fluorescence and photoacoustic imaging-guided cancer chemo-radiotherapy using hybrid plasmonic-fluorescent assemblies

Multimodal imaging in the second near-infrared window(NIR-II)guided cancer therapy is a highly precise and efficient cancer theranostic strategy.However,it is still a challenge to develop activated NIR-II optical imaging and therapy agents.In this study,we develop a pH-responsive hybrid plasmonic-fluorescent vesicle by self-assembly of amphiphilic plasmonic nanogapped gold nanorod(AuNNR)and fluorescent down-conversion nanoparticles(DCNP)(AuNNR-DCNP Ve),showing remarkable and activated NIR-II fluorescence(FL)/NIR-II photoacoustic(PA)imaging performances.The hybrid vesicle also exhibited superior loading capacity of doxorubicin as a superior drug carrier and efficient radiosensitizer for X-ray-induced radiotherapy.Interestingly,the accumulated hybrid AuNNR-DCNP Ve in the tumor resulted in a recovery of NIR-II FL imaging signal and a variation in NIR-II PA imaging signal.Dual activated NIR-II PA and FL imaging of the hybrid vesicle could trace drug release and precisely guided cancer radiotherapy to ultimately reduce the side effects to healthy tissue.

Recent Development in X-Ray Imaging Technology:Future and Challenges

X-ray imaging is a low-cost,powerful technology that has been extensively used in medical diagnosis and industrial nondestructive inspection.The ability of X-rays to penetrate through the body presents great advances for noninvasive imaging of its internal structure.In particular,the technological importance of X-ray imaging has led to the rapid development of highperformance X-ray detectors and the associated imaging applications.Here,we present an overview of the recent development of X-ray imaging-related technologies since the discovery of X-rays in the 1890s and discuss the fundamental mechanism of diverse X-ray imaging instruments,as well as their advantages and disadvantages on X-ray imaging performance.We also highlight various applications of advanced X-ray imaging in a diversity of fields.We further discuss future research directions and challenges in developing advanced next-generation materials that are crucial to the fabrication of flexible,low-dose,highresolution X-ray imaging detectors.

Cargo-encapsulated cells for drug delivery

Synthetic micro-/nanoparticle(MNP)carriers,either organic or inorganic ones,have advanced considerably in recent years for drug delivery with the aim of enhancing drug solubility/stability,reducing systemic toxicity and increasing dosing at pathological sites(Chen and Liang,2018;Xiang et al.,2018).Specially,the properties of MNPs,such as size,morphology,or surface groups,can be easily modulated to maximize their potency in delivering drugs to the targeted areas(Ran and Xue,2018).Nevertheless,till now,only a handful of MNPs have been approved by the US Food and Drug Administration for clinical application.Although numerous proof-of-concept studies of MNPs in animal models are in progress or are being clinically evaluated,synthetic MNPs are still struggling to reach the clinical expectations.

Plasmonic anisotropic gold nanorods:Preparation and biomedical applications

Gold nanorods(AuNRs)have attracted tremendous interest in biomedical fields due to their unique optical properties,tunable surface plasmon,and excellent biocompatibility.Their biomedical applications are mainly influenced by near-infrared(NIR)light,which can guarantee deep penetration into human tissues with minimal loss.However,traditional single AuNRs are unable to carry medicine into the lesion regions.Furthermore,it is difficult for AuNR nanoparticles to be implemented in multimodal imagingguided synergetic therapy,which has limited the application of AuNRs in the field of theranostics.In recent years,researchers have made great strides in modifying gold nanorods into nanomaterials for the integration of diagnosis and treatment.After modifying different functionalized shells on the outsides of AuNRs,heterostructure AuNRs known as anisotropic gold nanorod(AAuNR)nanoparticles possessed bioimaging and cancer therapy abilities,as well as a variety of other amazing biomedical applications.In addition,AAuNR nanoparticles can combine biomedical imaging and therapy into one system to achieve multimodal bioimaging guided synergetic therapy.In this study,we presented a current review of the latest progress of different types of AAuNRs nanoparticles and their biomedical applications.Furthermore,the challenges and future development trends of AAuNR nanoparticles in the biomedical fields are discussed.

Disulfide-Containing Molecular Sticker Assists Cellular Delivery of DNA Nanoassemblies by Bypassing Endocytosis

The delivery efficiency of DNA nanoassemblies to the cytosol remains unsatisfactory due to endoand lysosomal entrapment and degradation,which restricts their bioanalytical and biomedical applications.Herein,the authors developed a disulfide-containing molecular sticker(DSMS)assisted approach to achieve efficient cytosolic delivery of DNA nanoassemblies.DSMS is designed to consist of a disulfide unit for thiol-mediated uptake and a guanidinium cation unit for strongly adhering to DNA nanoassemblies.After attaching with DSMS,a set of DNA nanoassemblies maintained their original three-dimensional features but had a different cellular internalization pathway.These results demonstrated that DSMS-DNA nanoassemblies complex did not enter the cells via endocytosis but instead entered through thiol-mediated direct uptake.Taking advantages of this facile assembly,universal applicability,and direct cytosolic delivery,DSMS might serve as a potent agent to facilitate the applications of DNA nanoassemblies in a variety of fields,such as bioimaging,drug delivery,and gene therapy.

Mesoporous radiosensitized nanoprobe for enhanced NIR-Ⅱ photoacoustic imaging-guided accurate radio-chemotherapy

Oxygen deficiency is a major obstacle to hypoxic-related cancer theranostics,and developing the oxygen production nanoplatforms received the widespread attention.However,it is remaining a challenge to structure a nanoplatform with hypoxia alleviation effect and imaging-guided cancer radiotherapy.Herein,we present a novel theranostics nanoplatform(Au NPs/UCNPs/WO_(3)@C)comprising of tungsten trioxide(WO3)that loaded gold nanoparticles(Au NPs)and up-conversion nanoparticles(UCNPs)for improved photoacoustic(PA)imaging performance in the second near infrared window(NIR-Ⅱ,900-1,700 nm).Au NPs/UCNPs/WO_(3)@C exhibited superior oxygen-generation effect and doxorubicin loading capacity,thus serving as an efficient radiosensitizer for radio-chemo anti-cancer therapy.Importantly,the accumulated Au NPs/UCNPs/WO_(3)@C in the tumor region led to the increased NIR-Ⅱ PA imaging signal and the blood oxygen saturation signal,which could enhance radiation sensitivity and accurately guiding cancer radiotherapy to reduce side effects on normal tissues.This study with proof-of-concept confirmed the multifaceted characteristics and encouraging potential of biomimetic Au NPs/UCNPs/WO_(3)@C for NIR-Ⅱ PA imaging-guided tumor therapeutics.

Recent Development in X-Ray Imaging Technology: Future and Challenges

X-ray imaging is a low-cost,powerful technology that has been extensively used in medical diagnosis and industrial nondestructive inspection.The ability of X-rays to penetrate through the body presents great advances for noninvasive imaging of its internal structure.In particular,the technological importance of X-ray imaging has led to the rapid development of highperformance X-ray detectors and the associated imaging applications.Here,we present an overview of the recent development of X-ray imaging-related technologies since the discovery of X-rays in the 1890s and discuss the fundamental mechanism of diverse X-ray imaging instruments,as well as their advantages and disadvantages on X-ray imaging performance.We also highlight various applications of advanced X-ray imaging in a diversity of fields.We further discuss future research directions and challenges in developing advanced next-generation materials that are crucial to the fabrication of flexible,low-dose,highresolution X-ray imaging detectors.