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The rapid and sensitive detection of 2,6-pyridinedicarboxylic acid (DPA), one of the main biomarkers of Bacillus anthracis, is of great significance for the screening and diagnosing of anthrax. Herein, a ratiometric fluorescent nanoprobe based on zeolite imidazolate framework-8 (ZIF-8)@AuNCs-Tb was constructed by embedding both gold nanoclusters (AuNCs) and terbium ions (Tb3+) into ZIF-8 for high-resolution visual detection of DPA. Due to the aggregation induced emission enhancement (AIE) effect, AuNCs embedded in ZIF-8 emit a strong orange fluorescence. When Tb3+ is coordinated with DPA added to the nanoprobe, it will emit a strong green fluorescence owing to the antenna effect. The results reveal that ZIF-8@AuNCs-Tb nanoprobe can detect DPA effectively with a good linear relationship in the range of 40–200 and 200–1000 μmol/L, the limit of detection (LOD) is estimated at 1.8 μmol/L (3σ/k). The proposed nanoprobe shows a remarkable selectivity for DPA and is quite easy to realize visualization based on the fluorescent color changing from orange to green, which has potential application in clinical diagnosis. The feasibility of this method was verified by standard addition recovery experiments simulating the release of DPA from spores.

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.

The uncontrollable synthesis of Prussian blue (PB) and its weak stability toward OH– are great challenges affecting its electrochemical biosensing application. Herein we utilize the unique properties of chitosan (CS) to realize the facile and controllable synthesis of a CS-PB nanocomposite and combine it with the urease-catalyzed deposition of polydopamine (PDA) for amplifying the electrochemical signal inhibition of PB to develop a novel immunosensing method for protein detection. The immunosensor was constructed on a CS-PB modified electrode, and a urease-functionalized silica nanoprobe was prepared for tracing its sandwich immunoassay toward the model analyte of carcinoembryonic antigen. Besides the electrochemical impedance effect of the quantitatively captured nanoprobes, their enzymatic reaction can release numerous OH– to destroy the PB crystals and also induce the PDA deposition onto the immunosensor. These caused drastic electrochemical signal inhibition to PB. Based on the above multi-signal amplification mechanism, the method exhibits a very low detection limit of 0.042 pg mL–1 along with a very wide linear range of six-order of magnitude. In addition, the CS-PB based immunosensor has excellent specificity, repeatability, stability and reliability. Thus this PB nanocomposite and the proposed electrochemical immunosensing method reveal a promising potential for future applications.

As a general mechanism, ligand-induced receptor clustering on cell membrane plays determinative roles in pattern recognition and transmembrane signaling. Nevertheless, probing the dynamic characteristics for the complicated interactions between receptor clusters remains difficult because of the lack of strategy for receptor cluster labeling and long-term monitoring in live cells. Herein, we proposed a data-mining-integrated plasmon coupling microscopy to study the dynamic cluster-cluster interactions on cell surface. The receptor clusters were activated and labeled with multivalent plasmonic nanoprobes, which enables the real-time monitoring of individual receptor clusters and the measurement of cluster-cluster interactions from the analysis of plasmonic coupling for the nanoprobe pairs beyond the diffraction limit. Using this method, we found that the protease-activated receptor 1 (PAR1) clusters would experience an initial contact and then form a weakly bound cluster-cluster complex, followed by cluster fusion to generate large-sized signaling complexes. The underlying state transitions for the cluster-cluster fusion process were uncovered using a data-mining technique named the K-means-based hidden Markov model with the scattering intensity of coupled nanoprobe pairs as observations. All of the findings from single-particle analysis and bulk measurements suggested that the allosteric inhibitors could suppress the dynamic transitions from the weakly bound cluster-cluster complexes to fused signaling complexes, leading to the subsequent downregulation of intracellular calcium signaling pathways. We believe that this strategy is promising for imaging and monitoring receptor clustering as well as protein phase separation on the cell surface in various biological and physiological processes.

This study aimed to develop a single photo emission computed tomography/fluorescence (SPECT/FL) bimodal imaging probe to image blood cells. Hyperbranched polyglycerol (HPG) was synthesized by anionic ring-opening polymerization. Succinic anhydride was used to functionalize HPG. Then, indocyanine green (ICG) was bound to HPG, with a 73.59% binding yield. Deferoxamine (DFO) was subsequently bound to ICG-HPG, and DFO-ICG-HPG was radiolabeled with technetium-99m, with 100% yield. The molecular weight of HPG in this study was found to be 6.8 kDa. In in vitro studies, the radiolabeled nanoconjugates remained stable even after 6 h (last timepoint when stability was assessed), and when the nanoconjugates were applied to K562 chronic myeloid leukemia cells, the highest cell viability was observed at a concentration of 5 mu g/mL and binding efficiency increased over time, reaching 30% at 6 h (last timepoint when binding efficiency was assessed). The results support the feasibility of the developed probe to image blood cells, which would be useful for applications such as detecting internal bleeding. [GRAPHICS] ., Ege University Research Fund [2018 FBE 006]; NIH/NCI Cancer Support Grant [P30 CA008748], This work was financially supported by Ege University Research Fund (2018 FBE 006) and partially presented at HEZARFEN International Congress of Science, Mathematics, and Engineering Sciences held in Izmir/Turkey on November 8-10, 2019. Dr. Omer Aras was partially supported through the NIH/NCI Cancer Support Grant P30 CA008748.

Sensitive and selective detection of hypochlorite is in great demand for food safety, especially in fresh cold chain products. However, the detection limit of traditional visible emission-based strategies cannot satisfy the requirement of ultrasensitive analysis in practical applications. In this work, we explored a novel luminescent nanoprobe in the near-infrared-II (NIR-II) window to greatly improve the hypochlorite detection limit for analysis of real milk samples, which was based on the fluorescence resonance energy-transfer process between the hypochlorite-responsive dye (FD1080) and the lanthanide-doped downconverted nanoparticles. Specifically, the NIR-II luminescence from Yb ions was first suppressed by FD1080 due to the energy-transfer mechanism. In the presence of hypochlorite, FD1080 was bleached to recover the luminescence. As a proof-of-concept, the optimal nanoprobe exhibited a linear luminescence recovery in the range of 0.1-1 nM with the detection limit of 0.0295 nM for hypochlorite. Real milk sample detection experiments showed that the probe had good accuracy and precision.

Graphical Abstract Stimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly “turn on” in response to excessive ROS and “turn off” in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics. Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-01136-4.

Introduction The use of environmentally benign resources for nanoparticles synthesis is consistently pushed to the front burner in a bid to ensure and enhance environmental protection and beneficiation. In this light, application of different plant parts for the reduction and stabilization of nanoparticles is gaining popularity. Materials and Methods In this contribution, we have exploited Securidaca inappendiculata stem extract (SISE), as the reducing and stabilizing agent for room temperature synthesis of highly stable and dispersed AgNPs. The major bioactive compounds in SISE were profiled using an ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-MS-QTOF-MS). Results and Discussion SISE could reduce silver salts to its nanoparticles almost instantaneously with a maximum absorption spectrum at 423 nm, under the optimal conditions. The fabricated SISE AgNPs was extensively characterized using FTIR, TEM, SEM, XRD, EDS, Zeta analysis/DLS and TGA/DTG analysis. SISE AgNPs with average particles size between 10–15 nm and a zeta potential value of −19.5 ± 1.8 mV was obtained. It was investigated for in-vitro biological applications by carrying out, antimicrobial, antioxidant, hemolytic, cytotoxicity and antidiabetic assays. It was found that SISE AgNPs exhibited potent antimicrobial capacity against some food borne microbes, good antioxidant property, while also demonstrating high biocompatibility. Moreover, with a view to extending further the applications SISE AgNPs, it was tested as a colorimetric nanoprobe for Hg2+ detection in aqueous environment, where good linearity between 0.10 and 10.0 μM, with a detection limit of 26.5 nM, were obtained. The practicality of the probe was investigated by carrying out Hg2+ detection in water sample, with good accuracy and precision. Discussion Overall, this work introduced a new stabilizer for biocompatible AgNPs with far-reaching applications., Graphical Abstract

Lei Xia,1,* Li Wen,1,2,* Xiangxi Meng,1 Nina Zhou,1 Xiaoyi Guo,1 Teli Liu,1 Xiaoxia Xu,1 Feng Wang,1 Hua Zhu,1 Zhi Yang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, Guizhou, 550025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Zhu; Zhi YangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of ChinaTel +86 010-88196196; +86 010-88196495Email zhuhuananjing@163.com; pekyz@163.comBackground: In recent years, nuclear medicine imaging and therapy for prostate cancer have radically changed through the introduction of radiolabeled prostate-specific membrane antigen (PSMA)-binding peptides. However, these small molecular probes have some inherent limitations, including high nephrotoxicity and short circulation time, which limits their utility in biological systems.Methods and Results: In this study, organic melanin nanoparticles were used to directly label the long half-life radionuclide 124I (t1/2=100.8 h), and PSMA small molecular groups were efficiently bonded on the surface of nanoparticles to construct the PSMA-targeted long-retention nanoprobe 124I-PPMN, which has the potential to increase tumor uptake and prolong residence time. The results showed that the nanoprobe could substantially aggregate in the tumors of prostate cancer xenograft mice and was visible for more than 72 h. Positron Emission Computed Tomography (PET) imaging showed that the nanoprobe could be used for precise imaging of prostate cancer with high expression of PSMA. In addition, organic melanin nanoparticles labeled with an elemental radionuclide achieved a stable, metal-free structure. Cell experiments and mouse toxicity experiments indicated that the nanoprobe has high safety.Conclusion: The new nanoprobe constructed in this study has high specificity and biocompatibility. In the future, combined with the multifunctional potential of melanin nanoparticles, this nanoprobe is expected to be used in the integrated theranostics of prostate cancer.Keywords: prostate cancer, 124I, PET, PSMA, melanin nanoparticles

Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci. Fluorescent imaging in the second biological window has advantages for in vivo applications. Here, the authors synthesise a molecular nanoprobe which activates upon binding H2O2, generating both strong fluorescent NIR-II emission and ultrasound signal for multi-mode imaging of inflammatory diseases.

Lysosomal acidification is essential for its degradative function, and the flux of H+ correlated with that of K+ in lysosomes. However, there is little research on their correlation due to the lack of probes that can simultaneously image these two ions. To deeply understand the role of K+ in lysosomal acidification, here, we designed and fabricated a nanodevice using a K+-aptamer and two pH-triggered nanoswitches incorporated into a DNA triangular prism (DTP) as a dual signal response platform to simultaneously visualize K+ and pH in lysosomes by a fluorescence method. This strategy could conveniently integrate two signal recognition modules into one probe, so as to achieve the goal of sensitive detection of two kinds of signals in the same time and space, which is suitable for the detection of various signals with the correlation of concentration. By co-imaging both K+ and H+ in lysosomes, we found that the efflux of K+ was accompanied by a decrease of pH, which is of great value in understanding lysosomal acidification. Moreover, this strategy also has broad prospects as a versatile optical sensing platform for multiplexed analysis of other biomolecules in living cells.

The rapid development of advanced optical imaging methods including stimulated emission depletion (STED) and fluorescence lifetime imaging microscopy (FLIM) has provided powerful tools for real-time observation of submicrometer biotargets to achieve unprecedented spatial and temporal resolutions. However, the practical imaging qualities are often limited by the performance of fluorescent probes, leading to unsatisfactory results. In particular, long-term imaging of nucleic acids in living cells with STED and FLIM remained desirable yet challenging due to the lack of competent probes combining targeting specificity, biocompatibility, low power requirement, and photostability. In this work, we rationally designed and synthesized a nanosized carbonized polymer dot (CPD) material, CPDs-3, with highly efficient and photostable emission for the super-resolution and fluorescence lifetime imaging of nucleic acids in living cells. The as-fabricated nanoprobe showed responsive emission properties upon binding with nucleic acids, providing an excellent signal-to-noise ratio in both spatial and temporal dimensions. Moreover, the characteristic saturation intensity value of CPDs-3 was as low as 0.68 mW (0.23 MW/cm2), allowing the direct observation of chromatin structures with subdiffraction resolution (90 nm) at very low excitation (

Ratiometric fluorescence (FL) probes are highly desirable for highly sensitive and reliable assays. Dual-emitting carbonized polymer dots (CPDs) have great application prospects in building ratiometric FL sensors. However, dual-emitting CPDs are usually synthesized at high temperatures and high pressures, which not only increases the cost but also complicates the structure of CPDs. Here, we developed a facile strategy for the fabrication of dual-emitting CPDs at room temperature using tetrachlorobenzoquinone and ethylenediamine. The formation of CPDs was induced by Schiff base condensation reaction, enabling the following cross-linking polymerization process. The dual-emitting CPDs demonstrate good photostability and antioxidant capacity. Importantly, the typical dual-emission bands of the as-prepared CPDs are found to have a blue emission band at 445 nm with a maximum excitation of 350 nm and a yellow emission band at 575 nm with a maximum excitation of 440 nm. Based on the dual-emitting property of CPDs, a ratiometric FL nanoprobe is obtained for sensitive determination of vitamin B12 (VB12), as the inner filtering and static quenching effects between VB12 and CPDs allow effective quenching of the blue FL of CPDs, while the yellow FL is maintained. The established assay shows linear detection ranges of 0.25-100 μM with a low limit of detection of 0.14 μM. These findings provide new guidance for the facile preparation of CPDs with excellent dual-emitting optical properties, indicating good prospects in biosensing.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are a novel T1 contrast agent with good biocompatibility and switchable imaging signal that have not been widely applied for magnetic resonance imaging (MRI) because it is difficult to induce their relatively close ideal agglomeration. Here, by combining the microemulsion method with the biomineralization principle, a pH-responsive T2-T1 switchable MRI nanoprobe was constructed via the microemulsion-confined biomineralization of PEGylated USPIONs (PEG-USPIONs). The size of the formed CaCO3-coated PEG-USPION conjugates (PEG-USPIONs@CaCO3 nanoprobe) was uniform and controllable, and the preparation method was simple. The PEG-USPIONs inside the nanoconjugates agglomerate more tightly, and the T1-MRI signal of the nanoprobe is converted to the T2-MRI signal. When exposed to the acidic environment of the tumor tissue or internal organelles, the CaCO3-coating of the nanoprobes is dissolved, and free PEG-USPIONs are released, thus realizing the T1-weighted imaging of the tumors. The suitability of the PEG-USPIONs@CaCO3 nanoprobe for tumor MRI detection was successfully demonstrated using a mouse model bearing a subcutaneous 4T1 xenograft.

Dual-modal imaging systems could provide complementary information by taking advantage of each imaging modality. Herein, a fluorescence and 19F magnetic resonance imaging nanoprobe was developed through preparation of 19F-grafted fluorescent carbonized polymer dots (FCPDs). Both fluorescence and 19F nuclear magnetic resonance intensities of these FCPDs can be modulated by controlling the carbonization processes. The strong yellow fluorescence renders these FCPDs capable of cell fluorescence imaging. The in vitro and in vivo assessments demonstrated that the as-prepared FCPDs were suitable for 19F magnetic resonance imaging (19F MRI), which would provide great potential for biological imaging and early diagnosis applications. Moreover, this fabrication strategy offers a new protocol for 19F MRI nanoprobe design.

DNA-based nanoprobes have attracted extensive interest in the field of bioanalysis. Notably, engineered DNA nanoprobes that can respond to multiple pathological parameters are desirable to detect targets precisely. Here we design a split aptamer/DNAzyme (aptazyme)-based DNA probe for fluorescence detection of ATP and further develop a cooperatively activatable DNA nanoprobe for tumor-specific imaging of ATP in vivo. The DNA nanoprobes comprising split aptazyme-coated MnO2 nanovectors have high stability and are synergistically activated by multiple biomarkers, GSH and ATP. Upon stimuli by overexpressed GSH in tumor cells, this DNA nanoprobe can release the aptazyme and self-supply cofactor Mn2+ of the DNAzyme. Sequentially, intracellular ATP induces the proper folding of the split ATP aptamer and Mn2+-dependent DNAzyme, which activates the specific cleavage of substrate and generates the optical readout signal. This nanoprobe exhibits remarkable resistance to enzymatic degradation, satisfactory biosafety, identifies ATP specifically within cancer cells, and selectively lights up solid tumors. Our research provides a reliable method for ATP imaging in cancer cells and opens a new avenue for biochemical research and highly accurate disease diagnosis.

Precisely detecting biomarkers in living systems holds tremendous promise for disease diagnosis and monitoring. Herein, we developed a covalent organic framework (COF)-based tricolor fluorescent nanoprobe for simultaneously imaging biomarkers with different spatial locations in living cells. Briefly, a TAMRA-labeled survivin mRNA antisense nucleotide and a Cy5-labeled transmembrane glycoprotein mucin 1 (MUC1) aptamer were adsorbed on a nanoscale fluorescent COF. To enhance the interactions between COF nanoparticles (NPs) and nucleic acid molecules, a freezing method was employed for improving the nucleic acid loading density and ensuring detection performance. The fluorescence signals of dyes on DNAs were first quenched by the COF NPs. Internalization and distribution of the nanoprobes can be real-time visualized by the autofluorescence of COF NPs. In living cells, recognition between MUC1 with MUC1 aptamers causes fluorescence signal recovery of Cy5, while hybridization between survivin mRNA and its antisense DNA induces the signal recovery of TAMRA. Therefore, this COF-based multicolor nanoprobe could be employed for visualizing MUC1 on the cell membrane and survivin mRNA in the cytoplasm. Cancer cell-specific diagnostic imaging and monitoring of the process of cancer cell exosomes infecting normal cells using the nanoprobe were achieved. This work not only offers a versatile nanoprobe for bioanalysis but also provides new insights for developing novel COF-based nanoprobes.

One of the most severe diseases threatening the ageing population is Alzheimer’s disease (AD). Recent studies found that the cellular uptake of extracellular amyloid beta (Aβ) peptides can lead to a build-up of intracellular Aβ in certain neuronal cells, which consequently lead to the onset of AD pathogenesis. It is therefore hypothesized that the detection of cells that are involved in such Aβ uptake could facilitate the early diagnosis of AD. In this work, a magnetofluorescent nanoprobe was prepared conjugating dye-labeled Aβ42 peptides with iron oxide nanoparticles (IONPs). When incubated with SH-SY5Y cells, the cellular uptake of Aβ42-IONPs was enhanced, compared to that of bare IONPs. Further, by labelling SH-SY5Y and HCT-116 cells, it was found that the Aβ42-IONPs are selectively targeting the neuronal cells. This enhanced and specific neuronal targeting is attributed to the cellular uptake of extracellular amyloid by SH-SY5Y cells. In addition, the MR relaxivities of the Aβ42-IONPs are preserved after the peptides functionalization. The results suggest that the Aβ42 functionalized magnetofluorescent IONPs can be used as a bimodal probe to interrogate the cellular uptake of amyloid peptides.

An efficient electrogenerated chemiluminescence (ECL) nanoprobe (luminol-Au NPs-Ti3C2) was constructed based on Ti3C2Tx MXene (Ti3C2)-mediated in situ formation of Au NPs and anchoring luminol to fabricate a sensitive ECL biosensor for miRNA-155 detection. Herein, Ti3C2 with rich Ti vacancy defects was used as reducing agent, and Au NPs were generated in situ and anchored on the Ti3C2 (Au NPs-Ti3C2). Moreover, the Au NPs-Ti3C2 composites were used as a carrier and provided a large number of sites for the efficient linking of luminol through Au–N bonds to form stable luminol-Au NPs-Ti3C2. The immobilization of ECL emitters is a versatile strategy which not only shortens the electron transmission distance between luminol and electrode, but also provides naked catalytic predominated (111) facets of Au NPs with high electrocatalytic activity, significantly improving the ECL signal of luminol. Furthermore, a catalytic hairpin assembly (CHA) reaction was used, resulting in further amplification of the signal. As a result, the as-prepared ECL biosensor exhibited a linear range from 0.3 fM to 1 nM with a detection limit of 0.15 fM, and demonstrated high reliability of miRNA-155 detection even in human serum samples. The construction of a multifunctional ECL probe with excellent ECL emission opens a new chapter for the application of Ti3C2 in the field of bioanalysis.

An endogenous H2S-triggered intelligent optical nanoprobe combining second near-infrared (NIR-II) fluorescence with photoacoustic (PA) imaging can provide more comprehensive information to further improve the sensitivity and reliability of diagnosis for colorectal tumor, which is rarely explored. Herein, an endogenous H2S-triggered SiO2@Ag nanoprobe was designed for in situ dual-modal NIR-II/PA imaging of colorectal cancer. The designed dual-modal nanoprobe can be converted to SiO2@Ag2S after in situ biosynthesis via a sulfuration reaction with the over-expressed endogenous H2S in the colorectal tumor. More importantly, the designed SiO2@Ag nanoprobe exhibits high sensitivity and specificity for diagnosing colorectal cancer in vivo via dual-modal NIR-II/PA imaging. These results provide a new NIR-II/PA dual-modal imaging strategy for noninvasive intelligent detection of colorectal cancer.

A novel hybridized dual-targeting peptide-based nanoprobe was successfully designed by using the cyclic heptapeptide. This peptide has Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence, in which the RGD homing motif and KALK mitochondria-targeting motif were linked via amide bond. The designed peptide probe was further modified through covalent linkage to induce dual-imaging functionality, and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD-99mTc nanoparticles were tested for in vitro cytotoxicity, cellular uptake, and apoptosis-inducing functionalities. The cellular internalization, enhanced cytotoxicity and selective receptor binding capabilities against U87MG cells, excellent dual-imaging potential, improved apoptosis-inducing feature by damaging mitochondria, and in vivo preclinical investigations suggested that our newly designed novel hybridized peptide-based dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme. This study describes the development of dual-targeting self-assembled peptide nanoparticles followed by modifications using NIRF dye and radiolabeled with 99mTc for dual-imaging and enhanced therapeutic efficacy against brain tumor.

Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM's green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis.

The factors contributing to the survival of enveloped viruses (e.g., influenza and SARS-CoV-2) on fomite surfaces are of societal interest. The bacteriophage Phi6 is an enveloped viral surrogate commonly used to study viability. To investigate how viability changes during the evaporation of droplets on polypropylene, we conducted experiments using a fixed initial Phi6 concentration while systematically varying the culture concentration and composition (by amendment with 2% fetal bovine serum (FBS), 0.08 wt % BSA, or 0.5 wt % SDS). The results were consistent with the well-founded relative humidity (RH) effect on virus viability; however, the measured viability change was greater than that previously reported for droplets containing either inorganic salts or proteins alone, and the protein effects diverged in 1× Dulbecco's modified Eagle's medium (DMEM). We attribute this discrepancy to changes in virus distribution during droplet evaporation that arise due to the variable solute drying patterns (i.e., the "coffee-ring" effect) that are a function of the droplet biochemical composition. To test this hypothesis, we used surface-enhanced Raman spectroscopy (SERS) imaging and three types of gold nanoparticles (pH nanoprobe, positively charged (AuNPs(+)), and negatively charged (AuNPs(-))) as physical surrogates for Phi6 and determined that lower DMEM concentrations, as well as lower protein concentrations, suppressed the coffee-ring effect. This result was observed irrespective of particle surface charge. The trends in the coffee-ring effect correlate well with the measured changes in virus infectivity. The correlation suggests that conditions resulting in more concentrated coffee rings provide protective effects against inactivation when viruses and proteins aggregate.

The purpose of this study was to develop a colorimetric assay for detecting hydrogen peroxide (H2 O2 ) 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 H2 O2 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.

"On-demand" accurate imaging of multiple intracellular miRNAs will significantly improve the detection reliability and accuracy. However, the "always-active" design of traditional multicomponent detection probes enables them to passively recognize and output signals as soon as they encounter targets, which will inevitably impair the detection accuracy and, inevitably, result in false-positive signals. To address this scientific problem, in this work, we developed a near-infrared (NIR) light-activated multicomponent detection intelligent nanoprobe for spatially and temporally controlled on-demand accurate imaging of multiple intracellular miRNAs. The proposed intelligent nanoprobe is composed of a rationally designed UV light-responsive triangular DNA nano sucker (TDS) and upconversion nanoparticles (UCNPs), named UCNPs@TDS (UTDS), which can enter cells autonomously through endocytosis and enable remote regulation of on-demand accurate imaging for multiple intracellular miRNAs using NIR light illumination at a chosen time and place. It is worth noting that the most important highlight of the UTDS we designed in this work is that it can resist nonspecific activation as well as effectively avoid false-positive signals and improve the accuracy of imaging of multiple intracellular miRNAs. Moreover, distinguishing different kinds of cell lines with different miRNA expressions levels can be also achieved through this NIR light-activated intelligent UTDS, showing feasible prospects in precise imaging and disease diagnosis.

In food safety, Escherichia coli is one of the primary sources of food pollution and an essential factor affecting food safety. The purpose of this study is to establish a new method for rapid quantitative detection of E. coli O157:H7 in food based on silver nanocluster fluorescent probes. First, the antibody that can specifically recognize E. coli O157:H7 was combined with magnetic nanoparticles to form an immunomagnetic nanoprobe for capturing E. coli O157:H7, and then silver nanoprobes formed by adding aptamer-modified silver nanoclusters were added. Finally, a sandwich composite structure was formed. When the silver nanocluster fluorescent probes were explicitly combined with the magnetically adsorbed E. coli O157:H7, the silver nanocluster fluorescent probes which were not bound to the bacteria existed in the supernatant. Therefore, the content of pathogenic bacteria in the sample can be indirectly detected by measuring the fluorescence signal in the supernatant using a fluorescence spectrophotometer. The linear range of this method was 10–106 CFU/mL, and the detection limit of E. coli O157:H7 was 0.2549 CFU/mL in the buffer and 0.6031 CFU/mL in the milk simulation sample. Test with Salmonella, Shigella, and Klebsiella showed high specificity of this method for E. coli O157:H7. The detection process of this method does not exceed 2 h. This method demonstrates considerable potential as a rapid and sensitive tool for detecting a variety of bacterial pathogens.

Weak reactions are usually overlooked due to weak detectable features and susceptibility to interference from noise signals. Strategies for detecting weak reactions are essential for exploring reaction mechanisms and exploiting potential applications. Machine learning has recently been successfully used to identify patterns and trends in the data. Here, it is demonstrated that machine learning-based techniques can offer accurate local surface plasmon resonance (LSPR) scatterometry by improving the precision of the plasmonic scattering imaging in weak chemical reactions. Dark-field microscopy (DFM) imaging technique is the most effective method for high-sensitivity plasmonic nanoparticles LSPR scatterometry. Unfortunately, deviations caused by the instrument and operating errors are inevitable, and it is difficult to effectively detect the presence of weak reactions. Thus, introducing a machine learning calibration model to automatically calibrate the scattering signal of the nanoprobe in the reaction process can greatly improve the confidence of LSPR scatterometry under DFM imaging and allow DFM imaging to effectively monitor unobvious or weak reactions. By this approach, the weak oxidation of silver nanoparticles (AgNPs) in water by dissolved oxygen was successfully monitored. Moreover, a trivial reaction between AgNPs and mercury ions was detected in a dilute mercury solution with a concentration greater than 1.0 × 10-10 mol/L. These results suggest the great potential of the combination of LSPR scatterometry and machine learning as a method for imaging analysis and intelligent sensing.

Despite several attempts, incorporating biological detection that supplies necessary biological information into therapeutic nanotheranostics for hypoxic tumor treatments is considered to be in its infancy. It is therefore imperative to consolidate biological detection and desirable phototherapy into a single nanosystem for maximizing theranostic advantages. Herein, we develop a versatile nanoprobe through combined fluorescence resonance energy transfer (FRET) and oxygen-augmenting strategy, namely APT, which enables glycosylation detection, O2 self-sufficiency, and collaborative phototherapy. Such APT nanoprobes were constructed by depositing platinum onto gold nano-bipyramids (Au NBPs), linking FITC fluorophore-labeled AS1411 aptamers for introducing FRET donors, and by conjugating G-quadruplex intercalated with TMPyP4 to their surfaces via the SH-DNA chain. By installing FRET acceptors on the glycan of targeted EpCAM glycoprotein using the metabolic glycan labeling and click chemistry, FRET signals appear on the cancerous cell membranes, not normal cells, when donors and acceptors are within an appropriate distance. This actualizes protein-specific glycosylation visualization while revealing glycan-based changes correlated with tumor progression. Interestingly, the deposited platinum scavenges excessive H2O2 as artificial nanoenzymes to transform O2 that alleviates tumor hypoxia and simultaneously elevates singlet oxygen (1O2) for inducing cancer cell apoptosis. Notably, the significant hyperthermia devastation was elicited via APT nanoprobes with phenomenal photothermal therapy (PTT) efficiency (71.8%) for thermally ablating cancer cells, resulting in synergistically enhanced photodynamic-hyperthermia therapy. Consequently, APT nanoprobes nearly actualized thorough tumor ablation while demonstrating highly curative biosafety. This work offers a new paradigm to rationally explore a combined FRET and oxygen-augmenting strategy with a focus on nanotheranostics for hypoxic tumor elimination.

Staphylococcus aureus (S. aureus) is one of the foodborne pathogens that can cause infectious diseases and food poisoning. Herein, colorimetric and fluorescent dual-mode nanoprobes were developed for ultrasensitive detection of S. aureus to immediately respond to public health emergencies, reduce false positives, and improve measurement accuracy and persuasiveness. The nanoprobe consists of aptamer-labeled magnetic nanoparticles (apt-MNPs) as the capture signal probe and horseradish peroxidase and complementary DNA-functionalized upconversion nanoparticles (HRP-UCNPs-cDNA) as the chromogenic signal probe. In the absence of S. aureus, the probe forms an immune complex through base complementation with an observable signal. When S. aureus is introduced to this system, it preferentially binds to the apt-MNPs, releasing HRP-UCNPs-cDNA from the apt-MNPs and restoring the chromogenic probe signal. Under optimum conditions, an ultrasensitive assay of S. aureus was obtained, with limits of detection of 22 CFU mL-1 for fluorescence and 20 CFU mL-1 for colorimetry in a linear range of 56-5.6 × 106 CFU mL-1. Additionally, the standard plate counting method confirmed the reliability and accuracy of the established nanoprobe with an insignificant difference. Hence, the developed dual-mode platform has extensive application prospects for speedy and specific determination of S. aureus in meat.

The importance of tracing dopaminergic agents in the progression assessment of Parkinson's disease has boosted the demand for fast, sensitive, and real-time multi-analyte detection. Herein, visual and fingerprint fluorimetric patterns have been created by an optical sensor array to simultaneously detect and discriminate among levodopa, carbidopa, benserazide, and entacapone, as important dopaminergic agents. A dual emissive nanoprobe consisting of red quantum dots and blue carbon dots with an overall pink emission has been fabricated to provide unique emission patterns in the presence of the target analytes. The sensor elements in the array come from it's differential response in the absence and presence of cetyltrimethylammonium bromide under alkaline conditions. A smartphone camera was used to take photos from the solutions in the wells. Distinct changes in the spectral profiles along with vivid and concentration-dependent color variations led to visual discrimination of dopaminergic agents in a broad concentration range. The results of linear discriminant analysis revealed great discrimination accuracies. Different concentrations of the target analytes were excellently recognized in human urine. The high sensitivity of the array, which is a bonus to rapid, on-site, and visual discrimination of dopaminergic agents, holds great promise for routine analysis of real-world clinical samples.

The therapeutic efficacy of natural killer (NK) cells-based immunotherapy is greatly related with the survival of transplanted NK cells. However, no effective strategy was reported to monitor NK cell viability in adoptive immunotherapy in vivo . Herein, we develop a ratiometric NIR-II fluorescence imaging strategy to quantitively track and visualize the adoptive NK cell viability in vivo in real-time. The nanoprobe consists of lanthanide-based down-conversion nanoparticles (DCNP) coated with IR786s, a reactive oxygen species (ROS) sensitive to NIR dye, which was directly labeled with NK cells. Upon cell death, the excessive ROS generation occurred within NK cells, along with IR786s degradation, turning on NIR-II fluorescent signal at1550 nm of DCNP under 808-nm excitation, while the fluorescent signal at 1550 nm of DCNP under 980-nm excitation was stable. Such an intracellular ROS-induced ratiometric NIR-II fluorescent signal was validated to correlate well with NK cell viability in vivo . Using this nanoreporter, we further demonstrated that co-treatment with IL-2, IL-15, and IL-21 could improve NK cell viability in vivo , achieving enhanced immunotherapy for orthotopic hepatocellular carcinoma. Overall, this strategy allows for longitudinal and quantitative tracking of NK cell viability in NK cell-based immunotherapy.

Glioblastoma (GBM), one of the most common primary intracranial malignant tumours, is very difficult to be completely excised by surgery due to its irregular shape. Here, we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles (SPIONs) modified with indocyanine (Cy7) molecules and peptides (ANG or DANG) to locate malignant gliomas and guide accurate excision. Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro, and both could mediate precise aggregation of the nanoprobes at gliomas sites in in vivo magnetic resonance imaging (MRI) and ex vivo near-infrared (NIR) fluorescence imaging. However, compared with ANG/Cy7-SPIONs probes, DANG/Cy7-SPIONs probes exhibited better enhanced MR imaging effects. Combining all these features together, this MRI/NIR fluorescence imaging dual-modal nanoprobes modified with retro-enantio isomers of the peptide have the potential to accurately display GBMs preoperatively for precise imaging and intraoperatively for real-time imaging.

Revealing the relationship between reactive oxygen species (ROS) and levels of protein phosphorylation is of great significance for understanding the pathogenesis of diseases. Although mass spectrometry is used as a classical method for protein phosphorylation analysis, there are still some challenges to realize in vivo protein phosphorylation recognition. Herein, we designed and prepared an metal-organic framework (MOF)-based fluorescent nanoprobe with Zr(IV) and boronate ester as an active center, which achieved simultaneous recognition of ROS and phosphorylation sites. The ROS unit was constructed by 1,8-naphthalimide and boronate ester as a fluorophore and a recognition group, respectively. The specific interaction between Zr(IV) and a phosphate group was used to realize fluorescence imaging of phosphorylation sites. Using the advantages of two-photon property of the ROS recognition unit, the nanoprobe can effectively reduce the background fluorescence and thus improve the imaging sensitivity. Finally, the MOF-based nanoprobe was successfully applied to reveal the relationship between ROS and levels of phosphorylation in pneumonia mice, which illustrated that the ROS and phosphorylation levels in the process of pulmonary inflammation were obviously higher than those of the normal mice. This work provides feasible fluorescence tools that have important significance for revealing pathogenesis of diseases.

This research aimed to detect Escherichia coli O157:H7 in milk based on immunomagnetic probe separation technology and quenching effect of gold nanoparticles to Rhodamine B. Streptavidin-modified magnetic beads (MBs) were combined with biotin-modified antibodies to capture E. coli O157:H7 specifically. Gold nanoparticle (AuNPs) was incubated with sulfhydryl-modified aptamers (SH-Aptamers) to obtain the Aptamers-AuNPs probe. After magnetic beads captured target bacteria and formed a sandwich structure with the gold nanoprobe, Rhodamine B was added into complex to obtain fluorescent signal changes. Our results demonstrated that the established method could detect E. coli O157:H7 in the range of 10(1)–10(7) CFU/mL, and the limit of detection (LOD) was 0.35 CFU/mL in TBST buffer (pH = 7.4). In milk simulation samples, the LOD of this method was 1.03 CFU/mL. Our research provides a promising approach on the detection of E. coli O157:H7.

The accurate and sensitive detection of hydrogen peroxide (H2O2) is of practical significance in the fields of bioanalysis, medicine, environmental protection as well as food industry. Herein, we design and fabricate NaTb(SO4)2 nanoparticles (NPs) as novel fluorescent nanoprobes for H2O2 detection. The design strategy is based on the fluorescence quenching occurred during the oxidation of Tb(III) to Tb(IV) upon H2O2 addition. The sensing of NaTb(SO4)2 NPs to H2O2 is in a “turn-off” mode, and the sensitivity is tunable by the pH due to the pH-dependence of the oxidizing ability of H2O2. Superior to most of the reported H2O2 sensors, NaTb(SO4)2 NPs exhibit reliable stability in acidic environment and a more sensitive response to H2O2 with a limit of detection (LOD) down to 0.047 μM at pH = 3.2. Based on its high sensitivity and reliable stability, the NaTb(SO4)2 NPs is anticipated to find potential applications in the field of biosensors.

As key characteristic molecules, several H2S-activated probes have been explored for colon cancer studies. However, a few ratiometric fluorescence (FL) probes with NIR-II emissions have been reported for the quantitative detection of H2S in colon cancer in vivo. Here, we developed an in situ H2S-activatable ratiometric nanoprobe with two NIR-II emission signals for the detection of H2S and intelligently lighting up colon cancer. The nanoprobe comprised a down conversion nanoparticle (DCNP), which emitted NIR-II FL at 1550 nm on irradiation with a 980 nm laser (F1550Em, 980Ex). Further, human serum albumin (HSA) was combined with Ag+ on the surface of DCNP to form a DCNP@HSA-Ag+ nanoprobe. In the presence of H2S, Ag2S quantum dots (QDs) were formed in coated HSA, which emitted FL at approximately 1050 nm on irradiation with an 808 nm laser (F1050Em, 808Ex) through an H2S-induced chemical reaction between H2S and Ag+; however, the FL signal of DCNP was stable at 1550 nm (F1550Em, 980Ex), generating a H2S concentration-dependent ratiometric F1050Em, 808Ex/F1550Em, 980Ex signal. The NIR-II ratiometric nanoprobe was successfully used for the accurate quantitative detection of H2S and the detection of the precise location of colon cancer through an endogenous H2S-induced in situ reduction reaction to form Ag2S QDs. Thus, these findings provide a new strategy for the specific detection of targeted molecules and diagnosis of disease based on the in situ-activatable NIR-II ratiometric FL nanoprobe.

Purpose Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. Methods In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. Results The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. Conclusion To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications., Graphical Abstract

Constructing multifunctional plasmonic core-satellites (CS) nanoassembly for clinical cancer diagnosis and therapy has gained vast attention. Herein, we reported a doxorubicin (Dox)-loaded CS nanoprobe for microRNA (miRNA) detection, targeting drug release, and therapy evaluation. The plasmonic CS nanoprobe was constructed with uniformly distributional 50 nm (core) and 13 nm (satellites) gold nanoparticles (AuNPs), which were functionally assembled with a specific sequence of DNA and peptides. Anticancer drug Dox was loaded by intercalating into the GC-rich double strands. In the presence of target miRNA (miRNA-21 used as model), the constructed CS nanostructure was disassembled, producing characteristic localized surface plasmon resonance (LSPR) signals and releasing Dox. With the increase of the miRNA-21 concentration ranging from 0.01 to 1000 fM, a distinct blue shift of scattering spectra peak occurred, along with obvious color change from orange to green under a dark-field microscope (DFM), which can be used to detect miRNA at single-particle level. Meanwhile, it released Dox-induced apoptosis. Caspase-3 involved in apoptosis was then activated to cleave the specific peptide substrate, releasing fluorophore FAM from AuNPs. As a result, caspase-3 was detected based on restored fluorescence intensity, which was used to evaluate the therapy effectiveness. In a word, the multifunctional plasmonic CS nanoprobe can be used not only to image cellular miRNA-21 to distinguish tumor cells from normal cells, but also to release drugs and monitor the apoptotic process in situ by confocal imaging.

The cellular glucose detection remains a vital topic, which could provide some essential information about the glucose-based pathological and physiological processes. In this study, a smart polydopamine nanodots-based cost-effective fluorescence turn-on nanoprobe (denoted as PDA-Ag-GOx) for intracellular glucose detection is established. Silver nanoparticles (AgNPs) are directly formed in one step by the reduction of fluorescent polydopamine nanodots (PDADs) which have much phenolic hydroxyls on the surface. The fluorescence of PDADs could be quenched by AgNPs through surface plasmon-enhanced energy transfer (SPEET) from donor PDADs to acceptor AgNPs. Glucose oxidase (GOx) is modified on the PDA-Ag NPs by covalent bond. In the presence of glucose, GOx could catalyze glucose to produce H2O2 and gluconic acid. The generated acid and H2O2 would degrade AgNPs into Ag+, the PDADs release and restore its fluorescence. The proposed nanoprobe has some advantages, such as cost-effective, easy preparation, and excellent selectivity toward glucose, which could be successfully utilized to intracellular glucose imaging.

Ischemic stroke (IS) characterized with high morbidity and mortality rates is considered as one of the most dangerous brain diseases. The timely assessment of IS is crucial for making a clinical decision due to the severity of IS featured with time-dependence. Herein, we develop a highly reactive oxygen species (HROS)-responsive ratiometric near-infrared-II (NIR-II) nanoprobe based on a dye-sensitized system between IR-783 dye and lanthanide-doped nanoparticles. Once intravenously injected into the mice, the probe is rapidly accumulated at a lesion site by recognizing the activated endothelial cell or impaired blood-brain barrier (BBB) in the ischemic area and further responds to HROS, thereby allowing in vivo imaging of the oxidative stress level. The probe is not only able to discriminate the salvageable ischemic tissue from infarcted stroke core by visualizing the enriched degree of the probe at the lesion site but also can grade the salvageable ischemic tissue by analyzing the oxidative stress level. In addition, the ischemia area was clearly delineated by NIR-II luminescence imaging after cerebral ischemia for 30 min, which is significantly earlier than with the magnetic resonance imaging (MRI) method, thereby providing a practical tool for the timely assessing of IS.

Mercury (Hg) contamination of the major environmental matrices, arising from human indiscriminate pursuit of industrialization without recourse to environment beneficiation is rife and worrisome. Amongst all the different forms of Hg, huge interest has been devoted to the inorganic Hg2+ determination, especially in water. Herein, a creatinine (CRN) conjugated on 3,3′-dithiodipropionic acid di(N-hydroxysuccinimide ester) (DTSP) functionalized gold nanoparticles (Au@DTSP/CRN)-based colorimetric assay was developed for Hg2+ detection in water samples. The DTSP was used to functionalize gold nanoparticles through the Au–S interaction, so as to impart a significantly high stability on the fabricated Au@DTSP, while also conferring coordination capacity on the nanoparticles. The Au@DTSP can bind to the amino group of CRN through its N-hydroxysuccinimide ester moiety, with the formation of an amide bond. The generated optical probe Au@DTSP/CRN aggregated in the presence of Hg2+, with a distinct change of solution colors from ruby red, through purple and to blue-grey within 10 min. The detection limit of 28.5 nM was achieved with linear calibration curves within 0.10–0.35 and 0.35–4.00 μM, while using the absorbance ratio (A680/A521) as the analytical response. Recoveries of 99.0–103.2% were obtained and the relative standard deviations were less than 5.5%. The Au@DTSP/CRN nanoprobe was applied for quantitative determination of Hg2+ in real water samples without significant interference from other metal ions, which is a positive indication of its utilitarian potentiality for Hg2+ profiling in aqueous environment.

A simple and feasible approach was constructed for preparation of all inorganic cesium lead bromide perovskite nanocrystals (CsPbBr3 NCs) modified with tetraphenylporphyrin tetrasulfonic acid (TPPS). The CsPbBr3/TPPS nanocomposite has good water stability and exhibits a dual-emission property. Adopting the CsPbBr3/TPPS nanocomposite as a nanoprobe, a rapid, selective and sensitive ratiometric fluorescent method was developed for determination of sulfide ion. When sulfide ion was added into the CsPbBr3/TPPS nanocomposite, the bright green fluorescence of CsPbBr3 NCs at 520 nm was sharply quenched, whereas the red fluorescence of TPPS at 650 nm was hardly influenced. The quenching is possibly attributed to destruction of CsPbBr3 NCs via the formation of more stable PbS. This nanoprobe can determine sulfide ion over the range of 0.2–15.0 nmol·L−1 with a detection limit as low as 0.05 nmol·L−1. The relative standard deviation is 3.3% at 10.0 nmol·L−1 concentration level (n = 11). Sulfide ion content was successfully determined in different water samples by this nanoprobe.

The bifunctional moderator is urgently needed in the field of ratiometric electrochemiluminescence (ECL) sensing since it can mediate simultaneously two ECL signals to conveniently realize their opposite change trend. This work designed a novel dual-signal combined nanoprobe with carboxyl-functionalized poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadazole)] nanoparticles (c-PFBT NPs) as the anodic ECL probe and L-cysteine capped CdS quantum dots (L-CdS QDs) as the cathodic ECL probe, which performed a dual-signal output capability without any additional coreactants. More importantly, hydrogen peroxide (H2O2) produced in situ by enzyme-catalyzed reaction was developed as a bifunctional moderator for simultaneously regulating two signals. The dual-signal combined nanoprobe (c-PFBT NPs@CdS QDs) served as the matrix to immobilize acetylcholinesterase (AChE) and choline oxidase for organophosphorus (OPs) analysis. In the absence of OPs, H2O2 was produced by catalyzing the substrate acetylthiocholine (ATCl) with enzymes and it quenched the anodic ECL signal from c-PFBT NPs and simultaneously promoted the cathodic ECL signal from L-CdS QDs. When OPs was present, the activity of AChE was inhibited, the anodic signal would increase, and the cathodic signal would accordingly decrease. The integration of the bifunctional moderator H2O2 and dual-signal combined nanoprobe c-PFBT NPs@CdS QDs not only provides an attractive ECL platform for enzymatic sensing involving the generation or consumption of H2O2 but also paves a new pathway for other ratiometric ECL systems involving enzyme catalytic amplification for detecting antigens, antibodies, DNA, RNA, etc.