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The interaction of a focused X-ray beam with a sample in a scanning probe experiment can provide a variety of information about the interaction volume. In many scanning probe experiments X-ray fluorescence (XRF) is supplemented with measurements of the transmitted or scattered intensity using a pixelated detector. The automated extraction of different signals from an area pixelated detector is described, in particular the methodology for extracting differential phase contrast (DPC) is demonstrated and different processing methods are compared across a range of samples. The phase shift of the transmitted X-ray beam by the sample, extracted from DPC, is also compared with ptychography measurements to provide a qualitative and quantitative comparison. While ptychography produces a superior image, DPC can offer a simple, flexible method for phase contrast imaging which can provide fast results and feedback during an experiment; furthermore, for many science problems, such as registration of XRF in a lighter matrix, DPC can provide sufficient information to meet the experimental aims. As the DPC technique is a quantitative measurement, it can be expanded to spectroscopic studies and a demonstration of DPC for spectro-microscopy measurements is presented. Where ptychography can separate the absorption and phase shifts by the sample, quantitative interpretation of a DPC image or spectro-microscopy signal can only be performed directly when absorption is negligible or where the absorption contribution is known and the contributions can be fitted. [ABSTRACT FROM AUTHOR]

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient’s results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and −39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

As an emerging hybrid imaging modality, microwave-induced thermoacoustic imaging (MTAI), using microwaves as the excitation source and ultrasonic signals as the information carrier for combining the characteristics of high contrast of electromagnetic imaging and high resolution of ultrasound imaging, has shown broad prospects in biomedical and clinical applications. The imaging contrast depends on the microwave-absorption coefficient of the endogenous imaged tissue and the injected MTAI contrast agents. With systemically introduced functional nanoparticles, MTAI contrast and sensitivity can be further improved, and enables visualization of biological processes in vivo. In recent years, functional nanoparticles for MTAI have been developed to improve the performance and application range of MTAI in biomedical applications. This paper reviews the recent progress of functional nanoparticles for MTAI and their biomedical applications. The challenges and future directions of microwave thermoacoustic imaging with functional nanoparticles in the field of translational medicine are discussed.

Quantum dots are the serendipitous outcome of materials research. It is the tiny carbonaceous nanoparticles with diameters ranging from 1 to 10 nm. This review is a brief discussion of the synthesis, properties, and biomedical applicability of quantum dots, especially in herbal therapy. As quantum dots are highly polar, they can be surface decorated with several kinds of polar functionalities, such as polymeric molecules, small functional molecules, and so on. The review also consists of the basic physical and optical properties of quantum dots and their excitation―dependent properties in the application section. We focus on therapeutics, where quantum dots are used as drugs or imaging probes. Nanoprobes for several diagnostics are quite new in the biomedical research domain. Quantum dot―based nanoprobes are in high demand due to their excellent fluorescence, non-bleaching nature, biocompatibility, anchoring feasibility for several analytes, and fast point―of―care sensibility. Lastly, we also included a discussion on quantum dot―based drug delivery as phytomedicine.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential oxidative metabolites of organisms, which are closely related to physiological, pathological and pharmacological processes. The accurate detection of ROS/RNS is important for the understanding of biological processes, monitoring of pharmacological effects, and predicting the course of disease. The recently developed NIR nanoprobes based on upconversion nanoparticles (UCNPs) hold great prospects in sensitive and deep‐tissue detection of ROS/RNS, and considerable progress has been achieved so far. In this review, we systematically summarize the up‐to‐date advances of UCNPs‐based near‐infrared (NIR) probes for ROS/RNS sensing, and the potential challenges and perspectives for further research are also highlighted. We envision that such a research field will have a bright future for modern biomedical applications. [ABSTRACT FROM AUTHOR]

Schematic diagram of the preparation of CON@Au-Probe nanoprobe and the mechanism for target methylated DNA detection. [Display omitted] Covalent-organic framework nanosheets (CONs) have received increasing attention in various fields. However, large-scale and high-yield preparation and flexible functionalization of CONs remain a challenging task. Herein, we designed and fabricated a novel ultrathin (<5 nm) vinyl-functionalized CON in large scale (>80 mg) and high yield (>60 %) via an imine-exchange synthesis strategy. Through post-modification strategy, the vinyl-functionalized CONs were sequentially modified with thiols and Au nanoparticles with high distribution density (mass ratio of CONs to Au was about 4:1) and narrow size distribution (3.5 ± 0.5 nm). The synthesized hybrid nanosheets were employed as material platform to design a novel nanoprobe for ultrasensitive detection towards cancer-associated methylated DNA. Integrating site-specific base oxidation damage strategy and target cyclic amplification effect, the well-designed CONs-based nanoprobe achieved high sensitivity for detecting methylated DNA as low as 10 fM and ultrahigh specificity for distinguishing 0.0001% methylation level. Noteworthy, the nanoprobe was successfully applied to the analysis of DNA methylation in human colon cancer cells, expanding the application scope of CONs and opening a new horizon to develop novel CONs-based nanoprobes. [ABSTRACT FROM AUTHOR]

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 μg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field. [ABSTRACT FROM AUTHOR]

Novel anthracene-based Schiff base derivative (4-(anthracen-9-ylmethylene) amino)-5-phenyl-4H-1,2,4-triazole-3-thiol; AT2) is synthesized and utilized as an aggregation-induced emission-enhancement (AIEE) active probe to detect Zn2+ and Tyrosine. Ultraviolet-visible absorption/photoluminescence (UV-vis/PL) spectroscopy studies on the AIEE property of AT2 (in ethanol) with increasing water fractions (fw: 0–97.5%) confirm the J-type aggregation. Excellent sensor selectivity of AT2 to Zn2+ and its reversibility with Tyrosine are demonstrated with PL interrogations. 2:1 and 1:1 stoichiometry and binding sites of AT2-Zn2+ and Tyrosine-Zn2+ complexes are elucidated from Job plots, HR-mass, and 1H-NMR results. Nanomolar-level detection limits (LODs) of Zn2+ (179 nM) and Tyrosine (667 nM) and association constants (Kas) of 2.28 × 10−6 M−2 (for AT2-Zn2+) and 1.39 × 10−7 M−1 (for Tyrosine-Zn2+) are determined from standard deviation and linear fittings. Nanofiber formation in AIEE and aggregated/dispersed nanoparticles in the presence of the Zn2+/Tyrosine are supported by scanning-electron microscope (SEM), transmission-electron microscope (TEM), atomic-force microscope (AFM), and dynamic-light scattering (DLS) investigations. Density-functional theory (DFT) studies confirm an "On-Off" twisted intramolecular charge transfer/photo-induced electron transfer (TICT/PET) and "On-Off-On" PET mechanisms for AIEE and sensors, respectively. B16-F10 cellular and zebrafish imaging are conducted to support the applications of AIEE and sensors. [ABSTRACT FROM AUTHOR]

Shigella as a typical foodborne pathogen has strong survivability in the environment or food, leading to infectious diseases, yet its rapid detection technology with high selectivity and sensitivity remains challenging. In this study, complementary strand modified upconversion nanoparticles (UCNPs) can offer stable yellow-green fluorescence at 500–700 nm excited by a 980 nm laser. Importantly, Shigella aptamer modified gold nanoparticles (GNPs) formed by "Au−S" bond act as a fluorescence resonance energy transfer (FRET) donor and recognition element that can bind specifically to Shigella and significantly quench the fluorescence of complementary strand modified UCNPs. As a result, the fluorescence of our developed nanoprobe increased linearly with the increase in Shigella in a wide range from 1.2 × 102 to 1.2 × 108 CFU/mL and the detection limit was as low as 30 CFU/mL. Moreover, the fabricated upconversion fluorescence nanoprobe can achieve Shigella detection in contaminated chicken without enrichment in 1 h. [ABSTRACT FROM AUTHOR]

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine–glycine–aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

[Display omitted] • We introduced a novel triple signal amplification aptasensor based on GO-MWCNTs, Exo I, and hDNA-AuNPs-HRP system for TET detection. • This approach achieved a low detection limit of 3.3×10−4 ng/mL, with a range from 1×10−3 ng/mL to 1×103 ng/mL, demonstrating high specificity, repeatability, stability, and reliability. • The versatility of this approach suggests that it could potentially be extended to detect various small molecules, offering a potent and reliable method for food safety monitoring. Enhancing the sensitivity of targeted substance detection is crucial, yet prior research seldom incorporates more than two signal amplification methods. In this study, we introduced a novel triple signal amplification strategy for tetracycline detection using an aptasensor. This strategy integrates a graphene and multi-walled carbon nanotubes composite (GO-MWCNTs), Exonuclease I (Exo I), and a hybrid DNA-gold nanoparticle (AuNPs)-horseradish peroxidase (HRP) system. The GO-MWCNTs serve as a conductive carrier, boosting electron transfer for initial signal amplification. Exo I, targeting single-stranded DNA, facilitates target recovery and secondary signal amplification. The gold nanoprobe, through specific base pairing, binds to the tetracycline aptamer's complementary chains on the electrode surface. Horseradish peroxidase's catalytic action then generates a robust electrochemical signal, culminating in three-stage signal amplification. This optimized approach achieved a low detection limit of 3.3 × 10−4 ng mL−1, with a range from 1 × 10−3 ng mL−1 to 1 × 103 ng mL−1. Notably, the aptasensor demonstrated high selectivity, repeatability, stability, and reliability. These findings offer a promising reference for developing effective aptasensors in antibiotic detection. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) holds a vital role in biological systems, serving diverse cellular functions. Selective determination of GSH over cysteine (Cys) and homocysteine (Hcy) stays challenging due to the shared functional groups among these biothiols. In this study, a versatile Eu-doped carbon dots (Eu-CDs) nanoprobe has been developed for the exceptionally sensitive and selective detection of GSH in biological fluids. The synthesized Eu-CDs exhibited high solubility in water, stability to salt and pH variations, and consistent fluorescence emission, boasting a quantum yield of 40.67 %. Following the optimization of detection parameters, a robust linear relationship for GSH was established in the concentration range of 0.0–50 μM, with a detection limit of 0.03 μM. The viability of the technique in actual samples was evaluated by successfully measuring the GSH in urine and human serum samples with a range recovery from 90.6 % to 98.5 %. Furthermore, Eu-CDs proved to be exceptionally suitable for imaging Hela cells owing to their low cytotoxicity and remarkable biocompatibility. As a result, the developed fluorescent biosensor demonstrated significant potential for widespread application in clinical diagnostic analyses. [Display omitted] • A fluorescent nanoprobe containing Eu-doped carbon dots were used to detect GSH. • The developed nanoprobe exhibited exceptional selectivity and sensitivity to GSH. • Determination of the GSH in urine and human serum samples with favorable recovery was proved. • Eu-CDs proved suitable for imaging Hela cells, primarily owing to their minimal cytotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new class of NIR-LED photostimulated luminescence (PSL) nanoprobes based on SrS:Eu2+,Dy3+@SrS NCs is proposed. • The stimulation band of these SrS:Eu2+,Dy3+@SrS NCs spans from 700 to 1400 nm. • A PSL duration time longer than 2 h is achieved upon 808-nm LED stimulation. • These SrS:Eu2+,Dy3+@SrS nanoprobes are exploited for tumor-targeted imaging in zebrafish. Near-infrared (NIR) photostimulated luminescence (PSL) nanocrystals (NCs) exhibit deep penetrability and low autofluorescence, recently evoking extensive interest for their application in biosensing. Nevertheless, most of the NIR PSL NCs encounter substantial constraints in biomedicine applications, primarily stemming from the necessity of high-power diode laser stimulation or their larger particle size. Herein, we design a new class of NIR light-emitting diode (LED) PSL NCs based on SrS:Eu2+ NCs, which were coated with SrS shell to improve their stability and photoluminescence (PL) intensity. The trap depth and density of the NCs were further tailored through thermal annealing and Dy3+ co-doping, resulting in efficient NIR PSL with a duration time longer than 2 h by stimulation with an NIR LED in a broad region within 700–1400 nm. Benefiting from their excellent NIR PSL, we showcased the potential of SrS:Eu2+,Dy3+@SrS NCs as sensitive nanoprobes for tumor-targeted imaging in zebrafish with a signal-to-noise ratio of 18.9. These findings demonstrate the significant promise of the proposed SrS:Eu2+,Dy3+@SrS nanoprobes for in vivo bioimaging, which may pave the way for the development of effective NIR PSL nanoprobes for diverse bioapplications in the future. [ABSTRACT FROM AUTHOR]

Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare.

For ratiometrically imaging peroxynitrite (ONOO−) in living cells, we devised and fabricated a novel fluorescent nanoprobe, NC-NP530/460, in this study. To achieve ratiometric fluorescence response towards ONOO−, NC-NP530/460 used 3-(2-benzothiazolyl) coumarin (Cou-Bz) as the internal reference and 1,8-naphthimide derivative (Naph-PN) as a fluorescent ONOO− probe. These compounds were incorporated into an amphiphilic block polymer called Pluronic F-127. In addition to an ultrafast response to ONOO−, NC-NP530/460 also showed great selectivity and sensitive detection (detection limit was 4.51 μM). It was important to note that NC-NP530/460 demonstrated solid performance for ONOO− fluorescence ratio imaging in living cells, highlighting its potential for ONOO−-related chemical biology research. [ABSTRACT FROM AUTHOR]

A dual-emission fluorescent (FL) probe was constructed by coordinating Cu2+ of copper metal–organic frameworks (Cu-MOFs) with − COO− group of carbon dots (CDs) for pesticide thiophanate-methyl (TM) determination. TM was recognized by organic ligands (H2BDC and H2BDC-NH2) of Cu-MOFs via π stacking. Due to the higher affinity of Cu2+ to TM than ligands and CDs, TM chelated with Cu2+ to form TM-Cu complex. Thus coordination of Cu-MOFs was damaged and the ligands were released resulting in the FL intensity increase of Cu-MOFs (F430). And also CDs were released from CDs@Cu-MOFs hybrids and electron transfer from CDs to CuMOFs was inhibited, leading to the FL intensity increase of CDs (F600). The FL intensity ratio (F430/F600) showed a good linear relationship with TM concentrations of 0.0307–0.769 μmol L−1 with a limit of detection (LOD) of ~ 3.67 nmol L−1. The probe was successfully applied to detect TM in spiked food samples with satisfactory recoveries of 93.1–113%. Additionally, visual detection of TM was achieved according to the fluorescence color variation from blue to carmine, indicating promising application of CDs@Cu-MOFs probe. [ABSTRACT FROM AUTHOR]

Bacterial contamination is an important factor causing food security issues. Among the bacteria, Escherichia coli is one of the main pathogens of food-borne microorganisms. However, traditional bacterial detection approaches cannot meet the requirements of real-time and on-site detection. Thus, it is of great significance to develop a rapid and accurate detection of bacteria in food to ensure food safety and safeguard human health. The pathogen heat-treatment module was designed in this paper based on the techniques including nanoprobe, pathogen heat-treatment, graphene transparent electrode (GTE), and adenosine triphosphate (ATP) bioluminescence technology. The system mainly consists of two parts: one is the optical detection unit; the other is the data processing unit. And it can quickly and automatically detect the number of bacterial colonies in food such as milk etc. The system uses not only the probe to capture and enrich E. coli by antigen-antibody interaction but also the heat treatment to increase the amount of ATP released from bacterial cells within five minutes. To enhance the detecting accuracy and sensitivity, the electric field generated by GTE is adopted in the system to enrich ATP. Compared to the other conventional methods, the linear correlation coefficient of the system can be reached 0.975, and the system meets the design requirements. Under the optimal experimental conditions, the detection can be completed within 25 min, and the detectable concentration of bacteria is in the range of 3.1 × 101–106 CFU/mL. This system satisfies the demands of a fast and on-site inspection. [ABSTRACT FROM AUTHOR]

Mitophagy has a critical role in maintaining cellular homeostasis through acidic lysosomes engulfing excess or impaired mitochondria, thereby pH fluctuation is one of the most significant indicators for tracking mitophagy. Then such precise pH tracking demands the fluorogenic probe that has tailored contemporaneous features, including mitochondrial-specificity, excellent biocompatibility, wide pH-sensitive range of 8.0–4.0, and especially quantitative ability. However, available molecular probes cannot simultaneously meet all the requirements since it is extremely difficult to integrate multiple functionalities into a single molecule. To fully address this issue, we herein integrate two fluorogenic pH sensitive units, a mitochondria-specific block, cell-penetrating facilitator, and biocompatible segments into an elegant silica nano scaffold, which greatly ensures the applicability for real-time tracking of pH fluctuations in mitophagy. Most significantly, at a single wavelength excitation, the integrated pH-sensitive units have spectra-distinguishable fluorescence towards alkaline and acidic pH in a broad range that covers mitochondrial and lysosomal pH, thus enabling a ratiometric analysis of pH variations during the whole mitophagy. This work also provides constructive insights into the fabrication of advanced fluorescent nanoprobes for diverse biomedical applications. [ABSTRACT FROM AUTHOR]

The dysregulation of pH has been linked to the onset of chronic conditions, such as cancer and neurological diseases. Consequently, the development of a highly sensitive tool for intracellular pH sensing is imperative to investigate the interplay between pH and the biochemical changes accompanying disease pathogenesis. Here, we present the development of a ratiometric fluorescent nanoprobe, NpRhoDot , designed for precisely measuring pH levels. We demonstrate its efficacy in sensitively reporting intracellular pH in monolayer A549 lung cancer cells, primary fibroblast cells, and 3D tumor spheroids derived from the DLD-1 colorectal adenocarcinoma cell line. NpRhoDot leverages a novel design, where stable carbon dots are functionalized with a pH-responsive ratiometric fluorescent probe comprising a naphthalimide-rhodamine moiety, NpRho1 . This design confers NpRhoDot with the high pH sensitivity characteristics of organic fluorescent probes, along with excellent photostability up to 1 h and biocompatibility of carbon dots. Through one-photon and two-photon fluorescence microscopy, we validate the reliability of NpRhoDot for biosensing intracellular pH in monolayer and three-dimensional tumor models from pH 4 to 7.

The development of minimally invasive surgery has greatly advanced precision tumor surgery, but sometime suffers from restricted visualization of the surgical field, especially during the removal of abdominal tumors. A 3-D inspection of tumors could be achieved by intravenously injecting tumor-selective fluorescent probes, whereas most of which are unable to instantly distinguish tumors via in situ spraying, which is urgently needed in the process of surgery in a convenient manner. In this study, this work has designed an injectable and sprayable fluorescent nanoprobe, termed Poly-g-BAT, to realize rapid tumor imaging in freshly dissected human colorectal tumors and animal models. Mechanistically, the incorporation of γ-glutamyl group facilitates the rapid internalization of Poly-g-BAT, and these internalized nanoprobes can be subsequently activated by intracellular NAD(P)H: quinone oxidoreductase-1 to release near-infrared fluorophores. As a result, Poly-g-BAT can achieve a superior tumor-to-normal ratio (TNR) up to 12.3 and enable a fast visualization (3 min after in situ spraying) of tumor boundaries in the xenograft tumor models, Apc min/+ mice models and fresh human tumor tissues. In addition, Poly-g-BAT is capable of identifying minimal premalignant lesions via intravenous injection., (© 2024 Wiley‐VCH GmbH.)

Vancomycin is employed to treat infections caused by gram-positive bacteria. Ensuring precise vancomycin dosages is essential to avoid the emergence of bacterial resistance. In the current study, a fluorescent nanoprobe was designed for vancomycin determination in exhaled breath condensate samples. The nanoprobe was based on carbon dots (CDs) doped with nitrogen, sulfur, phosphorus, and chlorine (NSPCl-doped CDs). Vancomycin significantly reduced the fluorescence of NSPCl-doped CDs and presented a quenching process in the analytical response of the probe within a concentration range of 0.01-2.0 μg mL -1 due to forming a non-fluorescent complex. The nanoprobe's intra-day and inter-day relative standard deviations were 1.4 % and 3.2 %, respectively. This nanoprobe was successfully used to determine vancomycin in the patients receiving this drug collected from the expiratory circuit of the mechanical ventilator., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elaheh Rhimpour reports financial support was provided by 10.13039/501100002958Tabriz University of Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Recently, physical tools for remotely stimulating mechanical force-sensitive and temperature-sensitive proteins to regulate intracellular pathways have opened up novel and exciting avenues for basic research and clinical applications. Among the numerous modes of physical stimulation, magnetic stimulation is significantly attractive for biological applications due to the advantages of depth penetration and spatial-temporally controlled transduction. Herein, the physicochemical parameters (e.g., shape, size, composition) that influence the magnetic properties of magnetic nanosystems as well as the characteristics of transient receptor potential vanilloid-1 (TRPV1) and transient receptor potential vanilloid-4 (TRPV4) channels are systematically summarized, which offer opportunities for magnetic manipulation of cell fate in a precise and effective manner. In addition, representative regulatory applications involving magnetic nanosystem-based TRPV1 and TRPV4 channel activation are highlighted, both at the cellular level and in animal models. Furthermore, perspectives on the further development of this magnetic stimulation mode are commented on, with emphasis on scientific limitations and possible directions for exploitation. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging., (© 2024 Wiley Periodicals LLC.)

Personalized radiotherapy strategies enabled by the construction of hypoxia-guided biological target volumes (BTVs) can overcome hypoxia-induced radioresistance by delivering high-dose radiotherapy to targeted hypoxic areas of the tumor. However, the construction of hypoxia-guided BTVs is difficult owing to lack of precise visualization of hypoxic areas. This study synthesizes a hypoxia-responsive T 1 , T 2 , T 2 mapping tri-modal MRI molecular nanoprobe (SPION@ND) and provides precise imaging of hypoxic tumor areas by utilizing the advantageous features of tri-modal magnetic resonance imaging (MRI). SPION@ND exhibits hypoxia-triggered dispersion-aggregation structural transformation. Dispersed SPION@ND can be used for routine clinical BTV construction using T 1 -contrast MRI. Conversely, aggregated SPION@ND can be used for tumor hypoxia imaging assessment using T 2 -contrast MRI. Moreover, by introducing T 2 mapping, this work designs a novel method (adjustable threshold-based hypoxia assessment) for the precise assessment of tumor hypoxia confidence area and hypoxia level. Eventually this work successfully obtains hypoxia tumor target and accurates hypoxia tumor target, and achieves a one-stop hypoxia-guided BTV construction. Compared to the positron emission tomography-based hypoxia assessment, SPION@ND provides a new method that allows safe and convenient imaging of hypoxic tumor areas in clinical settings., (© 2024 Wiley‐VCH GmbH.)

Summary: Circulating tumor cells (CTCs) are tumor cells that shed from the primary tumor and intravasate into the peripheral blood circulation system responsible for metastasis. Sensitive detection of CTCs from clinical samples can serve as an effective tool in cancer diagnosis and prognosis through liquid biopsy. Current CTC detection technologies mainly reply on the biomarker-mediated platforms including magnetic beads, microfluidic chips or size-sensitive microfiltration which can compromise detection sensitivity due to tumor heterogeneity. A more sensitive, biomarker independent CTCs isolation technique has been recently developed with the surface-charged superparamagnetic nanoprobe capable of different EMT subpopulation CTC capture from 1 mL clinical blood. In this review, this new strategy is compared with the conventional techniques on biomarker specificity, impact of protein corona, effect of glycolysis on cell surface charge, and accurate CTC identification. Correlations between CTC enumeration and molecular profiling in clinical blood and cancer prognosis are provided for clinical cancer management.

Bioaffinity nanoprobes are a type of biosensor that utilize the specific binding properties of biological molecules, such as antibodies, enzymes, and nucleic acids, for the detection of foodborne pathogens. These probes serve as nanosensors and can provide highly specific and sensitive detection of pathogens in food samples, making them an attractive option for food safety testing. The advantages of bioaffinity nanoprobes include their ability to detect low levels of pathogens, rapid analysis time, and cost-effectiveness. However, limitations include the need for specialized equipment and the potential for cross-reactivity with other biological molecules. Current research efforts focus on optimizing the performance of bioaffinity probes and expanding their application in the food industry. This article discusses relevant analytical methods, such as surface plasmon resonance (SPR) analysis, Fluorescence Resonance Energy Transfer (FRET) measurements, circular dichroism, and flow cytometry, that are used to evaluate the efficacy of bioaffinity nanoprobes. Additionally, it discusses advances in the development and application of biosensors in monitoring foodborne pathogens.

This study reports the synthesis of three types of carbon dots (CDs) prepared using citric acid as a carbon source and three different biomolecules (L‐serine, L‐threonine, and adenine) individually as an amine source. The obtained nanomaterials were characterized by powder XRD, TEM, FTIR, 13C NMR, distortionless enhancement by polarization transfer using a 135‐degree decoupler pulse (DEPT 135), dynamic light scattering (DLS), and Small‐Angle X‐ray Scattering (SAXS) techniques. After ensuring the formation of desired structures, prepared CDs were used for exploring the detection capabilities of different reactive nitrogen species and reactive oxygen species. Following the screening of their detection capabilities specifically for nitric oxide, different sensing parameters viz the limit of detection, quenching constant, and interferences were evaluated. Among the synthesized CDs, the lowest detection limit of 0.1 μM was determined for the serine‐derived dots while 0.12 and 0.19 μM was obtained for adenine and threonine‐derived dots, respectively. Eventually, a possible sensing mechanism for the detection of NO by the prepared nanomaterials is proposed. [ABSTRACT FROM AUTHOR]

Drug resistance and relapse lead to high mortality in acute myeloid leukemia, and studies have shown that CXCR4 overexpression is highly correlated with poor prognosis and drug resistance in leukemia cells. Isolation and detection of AML cells with CXCR4 overexpression will be crucial to the treatment of AML. In this paper, magnetic nanoparticles were firstly prepared successfully by high-temperature thermal decomposition method, and then characterized by TEM, VSM and DLS. Subsequently CXCR4-targeted magnetic fluorescent nanoprobes conjugated with antibody 12G5 were constructed by stepwise coupling. In cell experiments, the obtained probes demonstrated excellent targeting efficacy to CXCR4 overexpressed AML cells HL-60. In addition, HL-60 cells labelled with the magnetic probes can be magnetic isolated successfully in one microfluidics chip, with efficiency of 82.92 ± 7.03%. Overall, this method utilizes the superiority of superparamagnetic nanomaterials and microfluidic technology to achieve the enrichment and capture of drug-resistant cells in a microfluidic chip, providing a new idea for the isolation and detective of drug-resistant acute myeloid leukemia cells. [ABSTRACT FROM AUTHOR]

Second near-infrared（NIR-Ⅱ）light has been a focus of attention due to its feature of deep tissue penetration and low tissue absorbance. It can be used in vascular imaging，nerve imaging or cell tracking，which is devoted to reveal cell migration and the mechanism of pathophysiology in order to find possible treatment options. It is not only be utilized to guide the tumor resection by deciding whether a tumor has metastasis，but also optimize the cell therapy by tracking commonly used cells such as stem cells and immune cells. This review summarizes the appliance of NIR-Ⅱ fluorescence imaging in cell tracking technology according to different cell types.Furthermore，the challenges and future prospects of NIR-based cell tracking technologies are also discussed. [ABSTRACT FROM AUTHOR]

At present, clinical diagnosis of breast cancer is based on the combination of pathological typesand molecular typing (immunohistochemistry). Yet, it is invasive and unable to show the relationship between keybiological molecules and clinical key information in situ and in real time. This paper introduces the latest researchprogress of molecular classification of breast cancer using molecular imaging technology. Fluorescence imaginghas high sensitivity and does not rely too much on image analysis. Thus, molecular classification information ofbreast cancer can be obtained in real time and multi-channel, quantitatively or semi quantitatively by using the cor‐responding fluorescent probes. Therefore, the development of safe and efficient near-infrared fluorescent molecu‐lar probes with strong tissue penetration is the focus of future fluorescence imaging technology and molecular clas‐sification of breast cancer

Abstract Fe-based single-atomic site catalysts (SASCs), with the natural metalloproteases-like active site structure, have attracted widespread attention in biocatalysis and biosensing. Precisely, controlling the isolated single-atom Fe-N-C active site structure is crucial to improve the SASCs’ performance. In this work, we use a facile ion-imprinting method (IIM) to synthesize isolated Fe-N-C single-atomic site catalysts (IIM-Fe-SASC). With this method, the ion-imprinting process can precisely control ion at the atomic level and form numerous well-defined single-atomic Fe-N-C sites. The IIM-Fe-SASC shows better peroxidase-like activities than that of non-imprinted references. Due to its excellent properties, IIM-Fe-SASC is an ideal nanoprobe used in the colorimetric biosensing of hydrogen peroxide (H2O2). Using IIM-Fe-SASC as the nanoprobe, in situ detection of H2O2 generated from MDA-MB-231 cells has been successfully demonstrated with satisfactory sensitivity and specificity. This work opens a novel and easy route in designing advanced SASC and provides a sensitive tool for intracellular H2O2 detection.

Drug-induced liver injury (DILI) poses a significant risk to human health. Increasing evidence indicates that the superoxide anion (O 2 •-), as the precursor of the other reactive oxygen species, is key in the pathological processes associated with DILI. Nonetheless, understanding of the mechanisms of DILI is difficult due to the lack of an imaging tool for monitoring the fluctuation of O 2 •- levels during the progression of DILI. Herein, we developed an upconversion nanoprobe (Rbh-UCNs) for in vivo ratiometric tracking of endogenous O 2 •- in DILI. In this design, the addition of O 2 •- triggers the luminescent resonance energy transfer between Rbh and UCNs, which significantly enhances absorption centered at 534 nm and translates into a distinct decrease of the UCL emission at 543 nm, while the UCL emission peak at 654 nm and 800 nm are not significantly affected, offering a ratiometric UCL signal for the quantitative detection of O 2 •-. In addition, Rbh-UCNs could effectively visualize endogenous O 2 •- in living cells, zebrafish, and liver tissues upon stimulation with PMA or cisplatin. More importantly, tissue imaging of the liver region of mice revealed that the fluctuation of O 2 •- levels is associated with DILI and the protective effect of L-carnitine against DILI. Altogether, this study provides an available method for a deeper comprehension of the mechanisms underlying DILI and accelerating the development process of hepatoprotective medicines. [Display omitted] • A O 2.•- upconversion nanoprobe was fabricated by the assembly of Rbh with CD-UCNs. • The probe utilize the UCL intensity ratio to accurately quantify O 2.•-. • The probe showed high selectivity and sensitivity to O 2.•-. • The probe could visualize O 2.•- in living cells and zebrafish under oxidative stress. • The probe was successfully employed for monitoring O 2.•- in DILI mice. [ABSTRACT FROM AUTHOR]

An organic-inorganic hybrid nanoprobe, namely LML-D-SBA@Eu3+-Gd3+, was constructed, with SBA-15 acting as the carrier material, and luminol and Eu3+ acting as fluorescence channels to achieve ratiometric signals that eliminate external interference (accurate detection). Gd3+ was used as a sensitizer to amplify the red emission of Eu3+ (ultrasensitive detection). In TCs detection, the luminol emission at 428 nm was quenched due to the photoinduced electron transfer mechanism, and the Eu3+ emission at 617 nm was sensitized due to the synergistic energy transfer from TCs and Gd3+ to Eu3+. The fluorescence intensity at 617 and 428 nm showed ratiometric changes as indicated by notable color changes from blue to red. The detection limits for TC and OTC were 0.21 and 0.08 ng/mL, respectively. To realize a facile, rapid, and cost-effective detection, we constructed a portable intelligent sensing platform based on smartphones, and it demonstrated great potential for on-site detection of TCs. • An organic-inorganic hybrid fluorescent nanoprobe Py/EDTA-SBA-15@Eu3+ was constructed • The combination of lanthanide ion, fluorescent molecule and mesoporous silica achieved exceptional detection performances • The ratiometric detection of tetracycline antibiotics was realized by recording the F 617 /F 384 values • The detection limits for oxytetracycline and tetracycline were 0.08 and 0.21 ng/mL, respectively • The nanoprobe and smartphone-based sensing platform were applied in tap water and honey samples [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is the most important standard for the entrance of clinical drugs into the pharmaceutical market. The elevation of superoxide anion (O 2 •-) during drug metabolism can mediate apoptosis of hepatocytes and further generation of liver damage. Therefore, developing an effective imaging method for evaluating O 2 •- levels during DILI is of great importance. However, current reported O 2 •- fluorescent probes either use short excitation wavelengths or a single intensity detection system, limiting the accurate quantification of O 2 •- in deep tissue in vivo. We developed a NIR-excited ratiometric nanoprobe (CyD-UCNPs) by assembly of O 2 •--sensitive hemicyanine dyes (CyD) on the surface of Tm/Er-codoped upconversion nanoparticles (UCNPs) with the assistance of α-cyclodextrin, which exhibited a robust "turn-on" ratiometric sensing signal. In vitro experiments indicated that CyD-UCNPs respond well to O 2 •- with high selectivity. Furthermore, by taking advantage of the outstanding optical properties produced by the luminescent resonance energy transfer between the UCNPs and CyD upon the excitation of 980 nm, the ratiometric upconversion luminescence signal of CyD-UCNPs was successfully utilized to monitor the fluctuation of O 2 •- levels under phorbol-12-myristate-13-acetate (PMA)/cisplatin-induced oxidative stress in living cells, liver tissues, and zebrafish. More importantly, endogenous change in O 2 •- levels in the liver sites of mice during DILI and its prevention with L-carnitine was visualized using CyD-UCNPs. This study provides a ratiometric NIR-excited imaging strategy for investigating the correlation between O 2 •- levels and DILI and its prevention, which is significant for early diagnosis of DILI and preclinical screening of anti-hepatotoxic drugs in vivo. [Display omitted] • A NIR-excited ratometric upconversion nanoprobe CyD-UCNPs for detecting O 2.•- based on LRET mechanism was reported. • This nanoprobe shows highly responsive ability for O 2.•- detection with distinct ratiometric UCL turn on. • This nanoprobe was successfully applied for monitoring of O 2.•- levels in living cells, zebrafish, and liver tissues under oxidative stress. • CyD-UCNPs has great potential in early diagnosis of drug-induced liver injury and screening of anti-hepatotoxic medicines. [ABSTRACT FROM AUTHOR]

Abstract Probiotics comprise a large group of microorganisms, which have different properties and thus confer different benefits. The use of probiotics has shown promising results in the management of diarrheal diseases. While the availability of probiotic products has flourished in the marketplace, there is limited guidance on the selection of probiotics for clinical use. This position paper is aimed at informing clinicians about the proper selection criteria of probiotics based on current evidence on strain‐specific efficacy and safety for the management of diarrheal diseases. Members of the working group discussed issues on probiotic use in clinical practice, which were then drafted into statements. Literature to support or refute the statements were gathered through a search of medical literature from 2011 to 2020. Recommendations were formulated based on the drafted statements and evidence gathered, revised as necessary, and finalized upon agreement of all members. Twelve statements and recommendations were developed covering the areas of quality control in the manufacturing of probiotics, criteria for selection of probiotics, and established evidence for use of probiotics in diarrheal diseases in adults and children. Recommendations for the use of specific probiotic strains in clinical practice were categorized as proven and probable efficacy based on strength of evidence. Robust evidence is available to support the use of probiotics for diarrheal diseases in clinical practice. Based on the results obtained, we strongly advocate the careful evaluation of products, including manufacturing practices, strain‐specific evidence, and contraindications for at‐risk populations when choosing probiotics for use in clinical practice.

[Display omitted] • Fluorescent ovalbumin stabilized gold nanoclusters (OVA-AuNCs) were employed to detect salicylaldehyde. • OVA-AuNCs were conjugated to salicylaldehyde via an imine linkage to form Salic_OVA-AuNCs nano-assembly. • Salic_OVA-AuNCs nanoprobe has been used for the detection of Hg(II) and folic acid. • Salic_OVA-AuNCs nanoprobe was applied to paper-strip sensing strategy for Hg(II) and folic acid detection. A sensitive and selective relay-based scheme for the detection of salicylaldehyde, Hg2+, and folic acid (FA) has been demonstrated using fluorescent ovalbumin functionalized gold nanoclusters (OVA-AuNCs, λ em = 655 nm) in this article. The OVA-AuNCs were conjugated to salicylaldehyde via an imine linkage to form Salic_OVA-AuNCs conjugate. The molecular docking study reveals that multiple functional groups and amino acid residues are involved in the interaction between salicylaldehyde and the OVA-AuNCs. The coupling of salicylaldehyde with OVA-AuNCs results in fluorescence quenching at 655 nm and concomitant formation of an emission band at 500 nm, which have leveraged to detect salicylaldehyde down to 2.02 µM. Following that, the Salic_OVA-AuNCs has been used for the detection of Hg2+ and FA. Several processes, such as internal charge transfer (ICT), photoinduced electron transfer (PET) and metallophilic interactions, are involved between the Salic_OVA-AuNCs nanoprobe and the analytes, which allowed to detect Hg2+ and FA down to 0.13 nM and 0.11 nM, respectively. The Salic_OVA-AuNCs nanoprobe has an additional naked-eye utility when applied to paper-strip sensing strategy for Hg2+ and FA detection. [ABSTRACT FROM AUTHOR]

In this study, a novel fluorescent nanoprobe (ZIF-90@FSS) was constructed using a zeolite imidazolium ester skeleton (ZIF-90) incorporating sodium fluorescein within its porous structure. Notably, this nanoprobe exhibited regular fluorescence "off" detection performance of Fe3+ in actual samples and living cells. The concentration range of 0–150 ng/mL exhibited a lowest detection limit of 0.26 ng/mL. A nanofiber paper-based platform (VL78/ZIF-90@FSS) was further developed by coupling the prepared nanoprobe to a multi-dimensional fiber paper via C N bonds, enabling rapid visual white light colorimetric and fluorescence imaging of Fe3+ within 2 min. The constructed nanoprobe and its paper-based detection platforms demonstrated a stable recovery range in tap water, beer, and soy sauce samples during spiking-recovery assessments. The recovery rates ranged from 98.46 % to 108.24 % for the nanoprobe and from 91.75 % to 108.71 % for the nanofiber paper-based platform. Therefore, the developed nano-fluorescent sensor and paper-based nanofiber sensing platform offer a promising strategy for the visual detection of Fe3+, while also presenting novel and valuable methods to investigate the regulatory mechanisms of Fe3+ in living cells. [Display omitted] • A novel fluorescent nanoprobe ZIF-90@FSS and paper-based nanofiber platform VL78/ZIF-90@FSS were developed. • ZIF-90@FSS and VL78/ZIF-90@FSS exhibit dynamic sensing and real-time imaging of Fe3+ in living cells and actual samples. • ZIF-90@FSS achieved fluorescence "off" detection of Fe3+ based on fluorescence energy transfer and absorption competition. • The ZIF-90@FSS nanoprobe exhibited rapid detection in vitro and spatiotemporal resolution for Fe3+ imaging in vivo. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible blindness worldwide and characterized by progressive loss of retinal ganglion cells (RGCs). As glaucoma progresses asymptomatically and the lack of specific biomarkers or noninvasive imaging tools during the early stage, it is often discovered at a relatively late stage without cure. Development of an effective tool for early diagnosis remains a necessity. As well known, endoplasmic reticulum (ER) stress and subsequent accumulation of reactive oxygen species (ROS) play a vital role in the development of glaucoma, with peroxynitrite (ONOO−) as one of the most abundant cytotoxic ROS. In this work, we constructed a novel near-infrared (NIR) fluorescent nanoprobe named ER-ONOO-NPs. It specifically and sensitively targets ER-associated ONOO− with low biotoxicity in cultured RGCs. Systematically applied to the NMDA-induced mouse model of glaucoma, ER-ONOO-NPs performs well for real-time dynamic monitoring of ONOO− fluctuations at the Ganglion cell layer of mice prior to RGCs apoptosis. Thus, our results suggest that the ER-targeted NIR fluorescent nanoprobe could be a noninvasive imaging tool for early diagnosis of glaucoma in high-risk population. [Display omitted] • An endoplasmic reticulum-targeted NIR fluorescent nanoprobe was developed for ONOO−. • The nanoprobe can detect ONOO− selectively and sensitively with fluorescence changes at 660 nm. • The fluorescence nanoprobe can image ER-associated ONOO− with low biotoxicity in cells. • The nanoprobe can monitor the level changes of ONOO− under endoplasmic reticulum stress in glaucoma. [ABSTRACT FROM AUTHOR]

Plant nanobionic sensors enable real-time monitoring of signaling molecules in plants by interfacing them with specifically designed nanoprobes, which have been acknowledged as species-independent analytical tools. In this study, we developed a plant nanobionic sensor for in vivo detection of extracellular adenosine triphosphate (eATP) in living plants by designing a novel second near-infrared (NIR-II) fluorescent metal–organic framework (MOF) nanoprobe. The NIR-II fluorescent nanoprobe (IR-1061 micelle@ZIF-90) with a sandwich structure was synthesized by successive encapsulation of the hydrophobic NIR-II dye IR-1061 with the amphipathic polymer DSPE-mPEG 2000 and MOF ZIF-90. Interestingly, coating ZIF-90 around IR-1061 micelles increased the NIR-II fluorescence 16.6-fold. Utilizing the ultrahigh NIR-II fluorescent emission of the designed nanoprobes and specific recognition of ZIF-90 to ATP, the nanoprobes were applied to spatial and temporal monitoring eATP in model and non-model plants under environmental stress. [ABSTRACT FROM AUTHOR]

A novel nanoassembly was constructed through encapsulating upconversion nanoparticles (UCNPs) into a metal–organic framework structure (ZIF-8), in which doxorubicin (DOX) was absorbed into pores of ZIF-8. The blue emission of UCNPs was quenched by DOX through the fluorescence resonance energy transfer (FRET) strategy. When the nanoprobe was exposed to food samples with different pH values, ZIF-8 collapsed to release DOX molecules, resulting in upconversion recovery. The porous structure of ZIF-8 provides abundant space for DOX absorption, which significantly improves the detection capacities and accuracy. It is shown that the probe has a good linear relationship when pH values vary from 2.5 to 7.4, and can distinguish pH variations as low as 0.5 in real samples. This strategy has been successfully used to determine food spoilage by determination of pH variations. [ABSTRACT FROM AUTHOR]

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine–glycine–aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy. Super-sensitive bifunctional nanoprobe that showed strong tumor-targeted imaging and antitumor therapeutic effects has been synthesized by one-step. This nanoparticle penetrated tumor cells to induce cell cycle arresting for cytotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

It has been challenging to integrate various medical imaging modalities into an ultra-small nanoparticle with good biocompatibility to build highly efficient multimodal imaging nanoprobes. A new manganese and dysprosium codoped carbon quantum dots (Mn,Dy-CQDs) with a mean diameter of 1.77 nm was synthesized for fluorescence imaging, T 1/ T 2-weighted magnetic resonance imaging (T 1/ T 2-weighted MRI), and x-ray computed tomography (CT) imaging using a simple one-step hydrothermal approach. The obtained Mn,Dy-CQDs showed good water solubility, long-term stability, strong stable fluorescence property (fluorescence quantum yield of 31.62%), and excellent biocompatibility. The cell imaging verified that the Mn,Dy-CQDs have high efficiency of fluorescence imaging. The Mn,Dy-CQDs, on the other hand, had a superior x-ray absorption performance (47.344 HU l gâˆ'1), a higher longitudinal relaxivity (r 1 = 7.47 mMâˆ'1 sâˆ'1), a higher transverse relaxivity (r 2 = 42.686 mMâˆ'1 sâˆ'1). In vitro T 1/ T 2-weighted MRI and CT imaging showed that Mn,Dy-CQDs can produce a strong contrast enhancement impact. To summarise, the Mn,Dy-CQDs may be used as a T 1/ T 2-weighted MRI/CT/fluorescent quadri-modal imaging nanoprobe, indicating that they have a lot of uses in biomedical multimode imaging and clinics. [ABSTRACT FROM AUTHOR]

Inorganic luminescent nanocrystals (NCs) doped with main-group ns2-metal ions have evoked tremendous interest in many technological fields owing to their superior optical properties. Herein, we report a new class of luminescent nanoprobes based on 5s2-metal Sb3+-doped CaS NCs that are excitable by using a near ultraviolet light-emitting diode. The optical properties and excited-state dynamics of Sb3+ in CaS NCs are comprehensively surveyed through temperature-dependent steady-state and transient photoluminescence (PL) spectroscopies. Owing to the strong electron-phonon coupling of Sb3+ in CaS NCs, Sb3+ ions experience a dynamic Jahn-Taller distortion on the excited state, which results in bright green PL of Sb3+ with a broad emission band, a large Stokes shift, and a high PL quantum yield up to 17.3%. By taking advantage of the intense PL of Sb3+, we show in proof-of-concept experiments the application of biotinylated CaS:Sb3+ NCs as sensitive luminescent nanoprobes for biotin receptor-targeted cancer cell imaging and zebrafish imaging with a high imaging contrast. These findings provide fundamental insights into the excited-state dynamics of Sb3+ in CaS NCs, thus laying a foundation for future design of novel and versatile luminescent nanoprobes via main-group ns2-metal doping. [ABSTRACT FROM AUTHOR]

Summary: Endogenous nitric oxide is important for living beings; hence, accurate and non-invasive detection of nitric oxide (NO) in situ is of significance. Benzothiadiazole-core chromophores are important near-infrared II (NIR-II) dyes, but such limitations as fluorescence quenching in aqueous media and non-activatable response constitute major barriers for biological applications. To address these issues, here we report an activatable nanoprobe, BNDA@HβCD, with aggregation-induced emission for detecting the biomarker NO. The molecular probe BNDA and 2-hydroxypropyl-β-cyclodextrin (HβCD) form the amphiphilic host-guest complex BNDA-HβCD, which readily forms nanoaggregates in aqueous media and thereby affords the nanoprobe BNDA@HβCD. NO reacts with the probe and generates the activated probe, which displays strong NIR-II fluorescence emission and optoacoustic signals. BNDA@HβCD can detect liver injury and monitor therapeutic outcome in a mouse model by detecting hepatic NO; it can also image NO in soybean sprouts. The results indicate that BNDA@HβCD is a robust tool for detecting NO in both animals and plants.

The purpose of this study was to develop a colorimetric assay for detecting hydrogen peroxide (H2O2) through a combination of using an aryl boronate (AB) derivative and gold nanoparticles (AuNPs). The unique optical property of AuNPs is applied to design a detection probe. The aggregation of AuNPs could be directly observed as a color change by the naked eye. A mannoside‐boronate‐sulfide (MBS) ligand was designed that contains an arylboronate (AB), a mannoside, and a thiol group. The thiol group bonds covalently with the surface of AuNPs to obtain MBS@AuNPs. The mannoside moiety recognizes concanavalin A (Con A), a lectin with four carbohydrate recognition sites that can specifically recognize the non‐reducing end of an α‐D‐mannoside or α‐D‐glucoside structure. The AB structure on MBS first reacts with H2O2 and then inserts an oxygen atom in the B−H bond, which triggers intramolecular electron rearrangement to cleave the covalent bond, resulting in a MBSt mixture. The MBS or MBSt is then modified to citrate‐coated AuNPs (c‐AuNPs) to have MBS@AuNPs or MBSt@AuNPs. When the MBS@AuNPs are incubated with Con A, the Con A recognizes multiple mannosides on the surface of the MBS@AuNPs. Subsequently, the MBS@AuNPs aggregate and the solution's color changes from red to purple, but this color change does not occur in the case of MBSt@AuNPs. The phenomenon can be observed by the naked eye. [ABSTRACT FROM AUTHOR]

Currently, stimulus-responsive nanomedicines are usually activated by a single cancer-associated biomarker and utilize different image/therapeutic agents for cancer imaging/therapy, which restricts the specificity of nanomedicine and complicates their design. Herein, we report a novel dual-locking theranostic nanoprobe (DL-P) based on near-infrared (NIR) hemicyanine CyNH 2 with two orthogonal stimuli of cancer cell lysosomal pH (first "lock")- and lysosome-overexpressed cathepsin B (CTB, second "lock")-triggered NIR fluorescence turn-on and drug activation to improve the specificity of cancer imaging and therapy. The fluorescence of CyNH 2 was initially quenched due to intramolecular charge transfer (ICT) but could be selectively activated under the dual-key stimulation of lysosomal pH and CTB to liberate CyNH 2 , resulting in strong NIR fluorescence turn-on for cancer imaging. Moreover, CyNH 2 caused mitochondrial dysfunction to inhibit cancer cell proliferation in the absence of laser irradiation, which can be used in cancer therapy. Compared with previously reported probes that respond to a single stimulus, this dual-locking nanoprobe that is responsive to two orthogonal stimuli triggers with integrated imaging and therapy function in a single agent exhibits increased selectivity and specificity, which provides a prospective strategy for precise cancer imaging and therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Xiumei Tian1 ,* Ao Zeng1 ,* Ziying Liu,1 Cunjing Zheng,2 Yuezi Wei,1 Peiheng Yang,1 Minru Zhang,1 Fanwen Yang,1 Fukang Xie1 1School of Basic Medical Sciences, Affiliated Stomatology Hospital, Guangzhou Medical University, Guangzhou 510182, People’s Republic of China; 2Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fukang Xie Tel +86 20 136 4231 6682Email 378141679@qq.comFanwen Yang Tel +86 20 135 0308 0690Fax +86 20 3710 3509Email yangfanwen@163.comBackground: Understanding the biocompatibility and biointeractions of nano-carbon quantum dots (nano-CQDs) in vitro and in vivo is important for assessing their potential risk to human health. In the previous research, the physical properties of CQDs synthesized by the laser ablation in liquid (LAL) method were analyzed in detail; however, possible bioapplications were not considered.Materials and Methods: CQDs were prepared by LAL and characterized by atomic force microscopy, fluorescence lifetime, absorption spectrum, Fourier-transform infrared spectroscopy, and dynamic light scattering. Their biocompatibility was evaluated in vitro using assays for cytotoxicity, apoptosis, and biodistribution and in vivo using immunotoxicity and the relative expression of genes. Cells were measured in vitro using fluorescence-lifetime imaging microscopy to analyze the biointeractions between CQDs and intracellular proteins.Results: There were no significant differences in biocompatibility between the CQDs and the negative control. The intracellular interactions had no impact on the optical imaging of CQDs upon intake by cells. Optical imaging of zebrafish showed the green fluorescence was well dispersed.Conclusion: We have demonstrated that the CQDs have an excellent biocompatibility and can be used as efficient optical nanoprobes for cell tracking and biomedical labeling except for L929 and PC-3M cells.Keywords: nanoprobe, immunotoxicity, biodistribution, biointeraction, optical imaging

Bimodal imaging combines two imaging modalities in order to benefit from their advantages and compensate the limitations of each modality. This technique could accurately detect diseases for diagnostic purposes. Nanoparticles simultaneously offer diagnostic data via various imaging modalities owing to their unique properties. Moreover, bimodal nanoprobes could be incorporated into theranostic systems for the design of multifunctional agents. Magnetic resonance imaging (MRI) and computed tomography (CT) are frequently used as noninvasive imaging modalities. These powerful, noninvasive diagnostic techniques used for the imaging of soft and hard tissues, respectively. However, MRI has low sensitivity and is not suitable for the imaging of bony structures. On the other hand, low soft tissue contrast is a major limitation of CT. Therefore, the development of various contrast agents that are proper for bimodal MRI/CT nanoprobes could largely influence modern medicine. This review aimed to specifically focus on the imaging properties of bimodal MRI/CT nanoprobes and their biomedical applications.

Objective(s): Contrast-enhanced magnetic resonance imaging (MRI) of breast cancer provides valuable data on the disease state of patients. Biocompatible nanoprobes are expected to play a pivotal role in medical diagnosis in the future owing to their prominent advantages. The present study aimed to introduce a novel biocompatible nanoprobe based on lipoproteins for breast cancer cell imaging.Materials and Methods: In this study, a biocompatible nanoprobe based on high-density lipoprotein was synthesized successfully. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used for material characterization, and cellular uptake and in-vitro and in-vivo imaging were investigated using the nanoprobe. Results: The nanoprobe could significantly reduce the relaxation time in the phantom and cancer cells with no toxicity in the studied cells. In addition, the nanoprobe demonstrated proper cellular uptake in the cancer cells. The in-vivo tumor images were obtained 30, 60, and 120 minutes after the injection of the nanoprobe (5.0 µmol/kg) via the tail vein, and the results indicated that the synthesized nanoprobe could be introduced as a potential MRI contrast agent. Conclusion: Future developments may allow the application of this nanoparticle to be used in pathological and physiological processes in preclinical models.

The solid-phase peptide synthesis (SPPS) strategy, as the main procedure of peptide manufacturing, has a profound impact on the research of peptides. The rapid development of nanotechnology is expected to promote the evolution of the solid phase to miniaturization, convenience and multi-function. In this work, silica-coated magnetic ferriferous oxide (Fe3O4) nanoparticles (MNP/SiO2) were used as new generation of solid phase for SPPS in Fmoc chemistry. The superparamagnetic solid phase facilitated a multi-step synthesis reaction due to its magnetic maneuverability, which could efficiently separate reaction intermediates, and were then redispersed in the next-step synthetic solution for peptide elongation. In addition, this strategy further allowed the simultaneous acquisition of magnetic nanoparticle–peptide conjugates as available bioprobes to examine the biological function of synthesized peptides. The feasibility of this novel magnetic nanoparticle-based solid phase peptide synthesis (MNP-SPPS) strategy was confirmed by the synthesis of arginine-glycine-aspartic acid-glycine-glycine (RGDGG) as a model pentapeptide. The simultaneously acquired magnetic nanoparticle–peptide conjugates (RGDGG-MNP/SiO2), possessing excellent biological functions, could be recognized and further internalized by tumor cells through receptor-mediated endocytosis, thereby achieving the extraction and removal of malignant cells in vitro under an external magnetic field. The RGDGG-MNP/SiO2 could further be used as a contrasting agent for tumor-targeting T2 magnetic resonance imaging in vivo. This study developed a novel MNP-SPPS strategy that could realize the simple synthesis of peptides, and the synchronously obtained nanoprobes could quickly detect the biological activity of the target synthetic sequence. This strategy may have broad application prospects in combinatorial chemistry and the construction of peptide libraries in the future.