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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.

Follicular thyroid carcinoma (FTC) is the second most common form of thyroid malignancy, and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma (PTC). Reliable approaches to preoperative FTC detection, however, remain to be established. Herein, a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging (PAI) of epidermal growth factor receptor (EGFR)-positive cells and tumors. These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro, and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo. Importantly, these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability, making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis. In addition, these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFR-positive tumors.

Compared with other transition metal Mxene derived quantum dots (MQDS), Ta-based Mxene quantum dots have good functionality, but Ta-based Mxene quantum dots and their applications have not been studied so far. In this paper, we report for the first time the synthesis of high fluorescence quantum yield (QY) N-doped Ta4C3 quantum dots (N-MQDs) using Ta4C3 quantum dots in acid reflux damaged Ta4C3 nanosheets as precursors and ethylenediamine as nitrogen source. The prepared N-MQDs have excellent blue photoluminescence (PL) properties, particle size is only 2.60 nm, QY is up to 23.4%, and good stability. In addition, it has been reported that N-MQDs can be used as fluorescent probe for detection of Fe3+ and remote force sensing analysis In liquid ion sensing, N-MQDS shows a unique selective quenching of Fe3+ with a detection limit as low as 2 μmol/L, and has great potential as a fast and super-sensitive fluorescent probe for the detection of heavy ion. More importantly, in solid mechanics sensing, the introduction of N-MQDs into self-healing hydrogels can be developed into a fluorescent hydrogel that can be used for accurate remote force measurement and applied in the field of mechanical sensing analysis. Therefore, Ta-based N-MQDs show excellent potential in the field of fluorescence sensing, which provides a door for multi-dimensional sensing of new materials in the future.

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.

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.

Herein, novel intrinsic dual-emitting carbon dots (CDs) are prepared through a one-step hydrothermal treatment of glucose and 3-nitroaniline in sulfuric acid solution and utilized for ratiometric determination of Cu2+ and aspartic acid (Asp). The CDs exhibited an interesting pH-switchable emission behavior displaying an intrinsic dual-emitting peak with emission maxima at 400 and 610 nm at pH 4.0–5.0. The presence of Cu2+ intensively quenched the first emission peak at 400 nm, but it had a negligible effect on the second emission peak. The ratiometric signal displayed a high selectively for Cu2+ over other metal ions and provided a linear response over the concentration range of 0.01–1.00 μM with a detection limit of 7.0 nM. Moreover, at pH 4.0, Asp was able to restore the quenched fluorescence of the CDs-Cu2+ system with a much more successful performance than other amino acids. This on-off-on fluorescence behavior provided a selective ratiometric fluorescence method for the determination of Asp in the concentration range of 0.2–15 μM. The acceptable detection results for Cu2+ in a river water sample (compared to Inductively Coupled Plasma (ICP) method) and for Asp in human serum samples confirmed the potential application of this ratiometric nanoprobe for sensing in real samples.

In this research, a hydroxyl group functionalized metal-organic framework (MOF), UiO-66-(OH)2, was synthesized as a “on-off-on” fluorescent switching nanoprobe for highly sensitive and selective detection of Fe3+, ascorbic acid (AA) and acid phosphatase (ACP). UiO-66-(OH)2 emits yellow-green light under ultraviolet light, when Fe3+ was added, Fe3+ was chelated with hydroxyl group, the electrons in the excited state S1 of the MOF transferred to the half-filled 3d orbits of Fe3+, resulting in fluorescence quenching because of the nonradiative electron/hole recombination annihilation. AA could reduce Fe3+ to Fe2+, which can destroy the electron transfer between UiO-66-(OH)2 and Fe3+ after AA adding, resulted in nonoccurrence of the nonradiative electron transfer, leading to the recovery of UiO-66-(OH)2 fluorescence intensity. The probe can also be used to detect ACP based on the enzymolysis of 2-phospho- l -ascorbic acid (AAP) to produce AA. Benefitting from the hydroxyl group and the characteristics of UiO-66, including the high porosity and large surface area, the developed UiO-66-(OH)2 showed extensive advantages as a fluorescent probe for detection of multi-component, such as high sensitivity and selectivity, colorimetric detection, fast response kinetics and easy to operate, economical and secure. This is the first time to use active group functionalized MOFs as a multi-component sensor for these three substances detection.

Peptide modified nanoparticles have emerged as powerful tools for enhanced cancer diagnosis and novel treatment strategies. Here, human programmed death-ligand 1 (PD-L1) peptides were used for the first time for the modification of gold nanoprisms (GNPs) to enhance targeting efficiency. A multifunctional nanoprobe was developed that the GNPs@PEG/Ce6-PD-L1 peptide (GNPs@PEG/Ce6-P) was used for imaging-guided photothermal/photodynamic therapy by using the targeting effect of PD-L1. Both confocal imaging and flow cytometry experiments demonstrated a remarkable affinity of the as-prepared nanoprobes GNPs@PEG/Ce6-P to lung cancer cells (HCC827), which have a high PD-L1 expression. Subsequent in vitro and in vivo experiments further demonstrated that the nanoprobes GNPs@PEG/Ce6-P not only allowed for real-time visualization via fluorescence (FL) imaging and photoacoustic (PA) imaging, but also served as phototherapy agents for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, treatments on human lung cancer cells-derived tumors demonstrated that the nanoprobes GNPs@PEG/Ce6-P could significantly suppress tumor growth through PTT and PDT from GNPs and Ce6, respectively. In conclusion, the as-prepared new nanoprobes show promising potential for nanomedicine with remarkable targeting ability for dual-mode imaging and enhanced PDT and PTT effects on lung cancer.

Herein, we report the development of sandwich type Surface Enhanced Raman Spectroscopy (SERS) immunosensor modified to be zwitterionic for the detection of soluble B7–H6 biomarker in blood serum from cervical cancer patients. Anti-fouling capture SERS substrate of biosensor based on gold (Au) thin film was modified with a self-assembled monolayer of zwitterionic l -cysteine to combat serum fouling and was then conjugated with NKp30 receptor protein to capture the B7–H6 biomarker in blood serum. The SERS nanoprobe based on spiky gold nanoparticles (AuNPs) was functionalized with ATP reporter molecule, that is stable at a wide range of pH, making the SERS signal reliable in complex media. Then, it was conjugated with anti-B7-H6 antibody forming the complex anti-B7-H6@ATP@AuNPs (i.e., SERS nanoprobe). The proposed immunosensor demonstrated high reproducibility for the quantitative detection of soluble tumor biomarker B7–H6 within the range of 10−10 M to 10−14 M with limit of detection (LOD) of 10−14 M or 10.8 fg mL−1, in the cancer patient serum, greatly exceeding (100 fold) the LOD of commercially available ELISA kits. Such low LOD is partially the result of zwitterionic modification which reduces the serum fouling by 55% compared to traditionally used BSA blocked capture substrates (i.e., control). Notably, this immunosensors demonstrated higher accuracy for detecting the B7–H6 biomarker in undiluted blood serum samples from cervical cancer patients and outperforms the currently available analytical techniques, making it reliable for point of care (POC) testing.

Adenosine triphosphate (ATP), as a high-energy phosphate compound that stores and releases energy in living cells, has an irreplaceable role in many physiological processes and maintenance of biological functions, and can be used as an indicator of many diseases. In this work, a composite nanoprobe, silver nanocluster (AgNC) @ molybdenum disulfide (MoS2), was designed to achieve in situ fluorescence imaging and quantitative analysis of intracellular ATP in HeLa cells by fluorescence spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). The probe was constructed based on the adsorption of DNA-AgNCs by MoS2 nanosheets, and the DNA-AgNCs were prepared with the ATP aptamer as a template, whose fluorescence was initially quenched by MoS2. When the probe was incubated into the cells, intracellular ATP recognized the aptamer sequence and caused the DNA-AgNCs to fall off the MoS2 nanosheets, resulting in fluorescence recovery. Here, AgNCs not only acted as a fluorescence label for imaging, but also as an element tag for quantitative analysis of intracellular ATP with the detection of 107Ag by ICP-MS. The ATP in HeLa cells detected by this method was 24.6 ± 1.7 nmol L−1, which was in good agreement with the test result of the ATP test kit (20.4 ± 0.8 nmol L−1). The proposed method has potential application in medical clinical diagnosis and evaluation of the body’s metabolic level via fluorescence imaging and ICP-MS detection of intracellular ATP.

As virus spread can lead to severe epidemics and pandemics associated with high mortality, it is necessary to have a highly sensitive detection method for viruses. Although various detection methods have been developed so far, current methods in detecting a virus require preprocessing and involve quite intricate processes of low sensitivity. Here, we have developed a virus detection method with a broad dynamic range and high sensitivity, based on immuno-complex formation between quantum dot (QD)-embedded silica nanoparticles (QD2) and magnetic beads. The multiple QD- containing QD2s showed 500 times stronger photoluminescence than individual QDs. When biotin was immobilized as a ligand, streptavidin was detected in a range of 10 zM to 10 nM. The clinical applicability of the QD2-based system was examined using the avian virus (i.e., H1N1 influenza virus), and it showed a detection range of 4.76 × 10−4 ∼ 3.2 hemagglutination unit/mL. This result is comparable to the polymerase chain reaction method, and is approximately 2100 times more sensitive than the conventional hemagglutination method. Since the QD2-based system could detect target molecules with high sensitivity without requiring an amplification step, it can be applied in various biomedical and clinical fields.

We report a self-assembled calcium-binding nanoprobe which emits a near-infrared fluorescence (NIRF) signal. We have designed a calcium-binding NIRF nanoprobe by chemically coupling alendronate (ALN), a specific targeting ligand, and NIRF-emitting Cy5.5-labeled dibenzocyclooctyne, to the two respective ends of azide-polyethylene glycol-NHS ester. Prepared ALN-PEG-Cy5.5 forms the self-assembled nanostructures and has high affinity for calcium phosphates-containing bone minerals. In addition, ALN-PEG-Cy5.5 can be employed to visualize intracellular calcium ion levels in vitro as well as normal bone tissues in vivo. These results suggest that our calcium-binding NIRF nanoprobe has a promising potential for calcium imaging in vitro and in vivo.

Aflatoxin M1 (AFM1) is generally used as a biomarker in urine for the assessment of aflatoxin exposure in humans and animals. However, there is no approach for the rapid and on-site monitoring of AFM1 level in urine. Here, we report a surface enhanced Raman scattering (SERS)-based lateral flow immunosensor built for such a purpose. Raman molecule 5,5-dithiobis-2-nitrobenzoic acid and anti-AFM1 monoclonal antibody were conjugated with Au (core)@Ag (shell) nanoparticle to serve as SERS nanoprobe. AFM1-bovine serum albumin was conjugated with gold nanoparticle and then applied onto nitrocellulose membrane as a visible "GOLD" test line. Quantitation of AFM1 was performed by the readout of Raman signal from the SERS nanoprobes captured on the test line. After optimizing experimental parameters, the detection limit of this immunosensor can achieve as low as 1.7 pg/mL of AFM1 in urine, which is far below the recommended tolerable level (30 pg/mL) of AFM1 in urine. The spiking experiment yielded 93.8%-111.3% recovery with coefficients of variation below 17% demonstrating high assay accuracy and precision. Moreover, this immunosensing assay is fast with an assay time below 20 min. Therefore, the developed immunosensor is a promising tool for the rapid assessment of aflatoxin exposure in the field.

The combination of different bioimaging techniques, mainly in the field of oncology, allows circumventing the defects associated with the individual imaging modalities, thus providing a more reliable diagnosis. The development of multimodal endogenous probes that are simultaneously suitable for various imaging modalities, such as magnetic resonance imaging (MRI), X-ray computed tomography (CT) and luminescent imaging (LI) is, therefore, highly recommended. Such probes should operate in the conditions imposed by the newest imaging equipment, such as MRI operating at high magnetic fields and dual-energy CT. They should show, as well, high photoluminescence emission intensity for their use in optical imaging and present good biocompatibility. In this context, we have designed a single nanoprobe, based on a core-shell architecture, composed of a luminescent Eu:BaLuF core surrounded by an external HoF shell that confers the probe with very high magnetic transverse relaxivity at high field. An intermediate, optically inert BaLuF layer was interposed between the core and the shell to hinder Eu–Ho cross-relaxation and avoid luminescence quenching. The presence of Ba and Lu, with different K-edges, allows for good X-ray attenuation at high and low voltages. The core-shell nanoparticles synthesized are good potential candidates as trimodal bioprobes for MRI at high field, dual-energy CT and luminescent imaging., This research was funded by the Spanish Ministry of Science, Innovation, and Universities (RTI2018-094426-B-I00). Siemens Healthcare S.L.U. also supported part of the research. We also acknowledge the use of the CNA’s ICTS NanoCT facilities and support from DGA and Fondos Feder for funding Bionanosurf (E15_17R) research group. S. Garcia-Embid acknowledges the Ministerio de Educación, Cultura y Deportes of Spanish Government for a FPU grant (FPU15/04482).

Objectives Postoperative pancreatic fistula (POPF) subsequent to pancreatectomy often causes activation of pancreatic juice, resulting in serious complications. In POPF, the types of pancreatic juices found are active and inactive, and the identification of these two types of pancreatic juice greatly contributes to the development of postoperative management after pancreatectomy. This study reports favorable results of the clinical application of the Forster resonance energy transfer (FRET) nanoprobe that was independently developed to distinguish between the active and inactive types of pancreatic juice. Methods The FRET nanoprobe developed was a nanoprotein capsule. It exuded a red color when the capsule structure was maintained. When activated protease in the pancreatic juice acts on it, the capsules are reduced quantitatively and FRET is abolished, resulting in a change in color from red to green. Pancreatic juice activation can be measured by the FRET signal. A total of 117 drainage fluid samples from 16 postpancreatoduodenectomy cases were obtained and evaluated. Results The diagnosis of pancreatic juice activation was possible using the FRET signal with a cut-off value of 1.6. Pancreatic juice activation was not associated with drainage fluid amylase (AMY) levels. The results demonstrated that pancreatic juice was activated when drainage fluid was infected. Conclusion The use of a FRET nanoprobe enabled real-time detection of the presence or absence of pancreatic juice activation in pancreatic fistula after pancreatic surgery. There was an adequate correlation between infection and pancreatic juice activation regardless of drain AMY levels.

Accurate temperature measurement plays an important role in a variety of industrial processes and scientific researches. In our work, the dual-mode temperature response nanoprobe CDs-Tb-TMPDPA containing a two-photon ligand (4-(2,4,6-trimethoxyphenyl)-pyridine-2,6-dicarboxylic acid, TMPDPA) sensitized Tb3+ as a temperature-sensitive unit and carbon dots (CDs) as photothermal reagent and a fluorescence reference unit, have been designed and synthesized. In this system, both the fluorescence intensity ratio and the fluorescence lifetime have a good response to temperature. In addition, due to the excellent photothermal conversion capability of CDs, photothermal antibacterial ability was also tested. Based on the temperature dependence of the fluorescence and the two-photon excitation characteristics of CDs-Tb-TMPDPA, the nanoprobe can also be used in the anti-counterfeiting. Our finding opens a new prospect for the use of two-photon sensitized dual-mode fluorescence thermometers.

A major obstacle in osteoarthritis (OA) theranostics is the lack of a timely and accurate monitoring method. It is hypothesized that the loss of anionic glycosaminoglycans (GAGs) in articular cartilage reflects the progression of OA. Thus, this study investigated the feasibility of photoacoustic imaging (PAI) applied for monitoring the in vivo course of OA progression via GAG-targeted cationic nanoprobes. The nanoprobes were synthesized through electrostatic attraction between poly-l-Lysine and melanin (PLL-MNPs). Cartilage explants with different concentrations of GAGs incubated with PLL-MNPs to test the relationship between GAGs content and PA signal intensity. GAG activity was then evaluated in vivo in destabilization of the medial meniscus (DMM) surgically-induced mouse model. To track OA progression over time, mice were imaged consistently for 10 weeks after OA-inducing surgery. X-ray was used to verify the superiority of PAI in detecting OA. The correlation between PAI data and histologic results was also analyzed. In vitro study demonstrated the ability of PLL-MNPs in sensitively detecting different GAGs concentrations. In vivo PAI exhibited significantly lower signal intensity from OA knees compared to normal knees. More importantly, PA signal intensity showed serial reduction over the course of OA, while X-ray showed visible joint destruction until 6 weeks. A decrease in GAGs content was confirmed by histologic examinations; moreover, histologic findings were well correlated with PAI results. Therefore, using cationic nanoprobe-enhanced PAI to detect the changes in GAG contents provides sensitive and consistent visualization of OA development. This approach will further facilitate OA theranostics and clinical translation. STATEMENT OF SIGNIFICANCE: The study of in vivo monitoring osteoarthritis (OA) is of high significance to tracking the trajectory of OA development and therapeutic monitoring. Here, we developed a cartilage-targeted cationic nanoprobe, poly-l-Lysine-melanin nanoparticles (PLL-MNPs), enhancing photoacoustic imaging (PAI) to monitor the progression of OA. The in vitro study demonstrated the ability of PLL-MNPs to detect different concentrations of GAGs with high sensitivity. We found that the contents of GAGs in vivo steadily decreased from the development of OA initial-stage to the end-point of our investigation via PAI; it reflected the course of OA in living subjects with high sensitivity. These results allow for further development in various aspects of OA research. It has potential for clinical translation and has a great impact on personalized medicine.

Fluorescent nanoprobe with good water dispersibility was synthesized by the coupling of fluorescent 1,8-naphthalimide dye (NANI) as well as biocompatible poly (ethylene glycol) (PEG) to cellulose nanocrystals (CNC). FTIR, TGA and XPS analysis confirmed the successful covalent conjugation of NANI and PEG. The rod-like morphology of CNC was generally retained after two-step successive grafting of NANI and PEG. The contact angle and transmittance measurements showed that the grafted PEG brushes improve the hydrophilicity of fluorescent CNC probes and their dispersibility in high-concentration NaCl solutions. The fluorescent CNC probe had good biocompatibility and was successfully used for the bioimaging of Hela cells in physiological environment at high salt concentration. Laser confocal microscopy showed that the fluorescent CNC probe can penetrate the cell membrane and disperse uniformly in the cell with good biocompatibility. The fluorescent CNC probe with nanometer size, strong fluorescence emission and high salt-tolerance possess potential application in biomedical field.

This work focused on the combination of CdTe and AgInS2 quantum dots in a dual-emission nanoprobe for the simultaneous determination of folic acid and Fe(II) in pharmaceutical formulations. The surface chemistry of the used QDs was amended with suitable capping ligands to obtain appropriate reactivity in terms of selectivity and sensitivity towards the target analytes. The implementation of PL-based sensing schemes combining multiple QDs of different nature, excited at the same wavelength and emitting at different ones, allowed to obtain a specific analyte-response profile. The first-order fluorescence data obtained from the whole emission spectra of the CdTe/AgInS2 combined nanoprobe upon interaction with folic acid and Fe(II) were processed by using chemometric tools, namely partial least-squares (PLS) and artificial neural network (ANN). This enabled to circumvent the selectivity issues commonly associated with the use of QDs prone to indiscriminate interaction with multiple species, which impair reliable and accurate quantification in complex matrices samples. ANN demonstrated to be the most efficient chemometric model for the simultaneous determination of both analytes in binary mixtures and pharmaceutical formulations due to the non-linear relationship between analyte concentration and fluorescence data that it could handle. The R2P and SEP% obtained for both analytes quantification in pharmaceutical formulations through ANN modelling ranged from 0.92 to 0.99 and 5.7-9.1%, respectively. The obtained results revealed that the developed approach is able to quantify, with high reliability and accuracy, more than one analyte in complex mixtures and real samples with pharmaceutical interest.

Fluorescent organic dots (O-dots) recently have emerged as a new class of promising contrast reagents for two-photon fluorescence (TPF) imaging. However, most of these developed two-photon absorption (TPA) O-dots have no tumor-targeting group, which hampers their wide application for targeted tumor imaging. Herein, we fabricated Sgc8c aptamer-mediated TPA O-dots as a proof-of-concept of the sensing platform for targeted imaging in live cells or deep tissues. The O-dots composed of trans-4-[p-(N, N-diethylamino)styryl]-4’-(dimethyl amino) stilbene (DEAS) emerged as TPA organic emissive cores and encapsulation by using poly (methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) as polymeric encapsulating matrix to form DEAS/PMMA-co-MAA O-dots via a co-precipitation strategy. The obtained O-dots enabled an extremely high TPA absorption cross-section, bright two-photon fluorescence (excitation at 720 nm; emission at 412 nm and 434 nm), excellent cell-permeability and high penetration depth. Sgc8c aptamer, as a protein tyrosine kinase-7 (PTK7) receptor-targetable ligand, was further anchored on the surface of O-dots to obtain DEAS/PMMA-co-MAA@Sgc8c nanoprobes by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)-mediated coupling reaction. Guided by Sgc8c aptamer, DEAS/PMMA-co-MAA@Sgc8c nanoprobes could be rapidly internalized into target acute lymphoblastic leukemia cells (CEM) cells with high specificity and great efficiency. It was also performed that two-photon images of TPA nanoprobes exhibited high two-photon brightness not only in target CEM cells, but also in mouse liver tissue slices even a depth of up to 210 μm. In our perception, it is highly promising that this nanoprobe provides a valuable tool for in vivo targeted imaging.

A simple, selective, and sensitive turn-off fluorescent assay for detecting of tetracycline in pharmaceutical dosage form based on inner filter effect (IFE) sensing platform has been described. In this IFE sensing strategy, N-doped carbon dots (CDs) were prepared by one-pot solvothermal synthesis using milk as a precursor and were directly used as a fluorophore in IFE. The prepared CDs were characterized by common spectroscopic and microscopic techniques. The CDs exhibited excitation-wavelength dependent emission with 10% as the fluorescence quantum yield. The fluorescence of CDs was decreased in correlation to the addition of absorber (tetracycline), as the excitation spectrum of the fluorophore (CDs) matches the absorption spectrum of the absorber. The present IFE-based sensing platform showed a good linear relationship from 2.0 µM to 200 µM (R2 = 0.9960) and provided a detection limit of 0.6 µM (signal-to-noise ratio of 3). Additionally, the cytotoxic effects of CDs were determined using normal healthy male Balb/C mice model treated with various doses of CDs and at the end of the study, no mortality or even no sign of toxicity was observed at oral doses of 100 and 200 mg/kg CDs in all treated animals. The proposed nanoprobe assay is a free from interferences, low-cost, biocompatible, and accurate for the detection of tetracycline in pharmaceutical formulation. Keywords: Carbon nanodots, Nitrogen doped, Milk-based carbon dots, Tetracycline, Quenching, Hydrothermal, Cytotoxicity, Pharmaceutical analysis

Multi-modality imaging agents are desirable for tumor diagnosis because they can provide more alternative and reliable information for accurate detection and therapy of diseases than single imaging technique. However, most reported conventional imaging agents have not been found to successfully overcome the disadvantages of traditional diagnoses such as sensitivity, spatial resolution, short half-decay time and complexity. Therefore, exploring a multifunctional nanocomposite with the combination of their individual modality characteristics has great impact on preoperative imaging and intraoperative diagnosis of cancer. In our study, mesoporous silica gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) specifically for preoperative and intraoperative imaging are designed and their imaging capability and biosafety are examined. They exhibit strong attenuation property for computed X-ray tomography (CT) imaging, high T1 relaxivity for magnetic resonance (MR) imaging capability and surface-enhanced Raman spectroscopy (SERS) signal with good dispersity and stability, which presents CT/MR/SERS multi-mode imaging performance of the tumor of mice within a given time. Furthermore, in vivo biodistribution and long-term toxicity studies reveal that the Gd-GERTs have good biocompatibility and bio-safety. Therefore, Gd-GERTs are of great potential as a multifunctional nanoplatform for accurate preoperative CT/MRI diagnosis and intraoperative Raman imaging-guide resection of cancers. STATEMENT OF SIGNIFICANCE: Recent advances in molecular imaging technology have provided a myriad of opportunities to prepare various nanomaterials for accurate diagnosis and response evaluation of cancer via different imaging modalities. However, single bioimaging modality is still challenging to overcome the issues such as sensitivity, spatial resolution, imaging speed and complexity for clinicians. In this work, we designed a kind of unique multifunctional nanoprobes with computed X-ray tomography/magnetic resonance/surface-enhanced Raman spectroscopy (CT/MR/SERS) triple-modal imaging capabilities. Multifunctional nanotags offer the capabilities of preoperative noninvasive CT/MR imaging for identification of tumors as well as intraoperative real-time SERS imaging for guidance of complete resection of tumors. These multifunctional nanoprobes show critical clinical significance on the improvement of tumor diagnosis and therapy.

Carbon dots (CDs) were synthesized from p-aminophenol and ethylenediamine via one-step under mild condition and used as a sensitive fluorescent nanoprobe for the activity determination of N-acetyl-β- d -glucosaminidase (NAG). In this assay, p-nitrophenol was in situ produced from p-nitrophenyl-β-D-N-acetyl-glucosaminide, which was exclusively hydrolyzed by NAG. The UV absorption peak of p-nitrophenol (maximum at 400 nm) overlapped the excitation peak of CDs with maximum wavelength at 415 nm, which caused the fluorescence decline of CDs based on inner filter effect. The activity of NAG was determined by the fluorescence changes. The assay is highly sensitive to NAG with a low detection limit of 0.75 U L−1 (K = 3) and showed a good linear relationship in the range from 1 to 45 U L−1. This CDs nanoprobe was successfully applied for the determination of NAG activity in human serum and urine samples.

A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine (Arg), exhibiting high sensitivity (the limit of detection, LOD, being 6.5 × 10−8 mol/L) and excellent selectivity and anti-interference ability, was fabricated through fluorescence resonance energy transfer (FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots (CDs). Arg can be quantitatively detected in the concentration range from 6.0 × 10−5 mol/L to 2.7 × 10−4 mol/L. Further, due to its ability to target mitochondrion and low cytotoxicity, intracellular Arg was successfully tracked through ratiometric fluorescence imaging.

Here, a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide (BPO) based on its deboronation. This gold nanoassembly (the BE-AuNPs12/65) was constructed via borate ester formation between large 4-mercaptophenylboronic acid (MPBA) modified AuNPs (the MPBA-AuNPs65, as cores) and small dopamine modified AuNPs (the DPA-AuNPs12, as satellites). Particularly, upon addition of BPO, it would trigger the deboronation for the BE-AuNPs12/65 probes accompanying with distinct color changes from blue, purple to wine red, which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond. By measuring the absorbance ratio at 665 nm and 545 nm, quantification of BPO was achieved in the range of 10.0–100.0 nmol/L, which could also be easily observed by naked eyes. The nanoprobe utilized a boronate deprotection mechanism and the LSPR properties of AuNPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L. The practical applicability of this assay was verified through successful determining BPO in flour samples, which demonstrated its great potentials in food safety field.

Endogenous hydrogen sulfide (H2S) exists in multiple physiological processes. In order to further understand the action mechanism of H2S in cells and human body, we proposed a smart surface-enhanced Raman scattering (SERS) nanoprobe, Au core-4-mercaptobenzonitrile-Ag shell nanoparticle (Au@4-MBN@Ag), for the detection of endogenous H2S in living cells based on the reaction between Ag shell and sulfide species. 4-MBN was selected as the SERS reporter to avoid interference from cellular molecules. With the sulfide concentration increasing, the Ag2S constantly formed, and consequently the SERS signal intensity of Au@4-MBN@Ag gradually decreased owing to the weaker SERS activity of Ag2S. With the nanoprobes, this method not only offers a high sensitivity for H2S detection at an nM level, but also achieves the goal of non-background analysis. It displays satisfactory anti-interference capability and a good linear relationship with sulfide concentration ranging from 50 nM to 500 μM, and an estimated detection limit is 0.14 nM. The Au@4-MBN@Ag nanoprobes were successfully applied to detect endogenous H2S in living HepG2 cells stimulated by pyridoxal 5-phosphate monohydrate. This work offers a potential analytical method in the related research of H2S physiological function.

Although numerous sensors have been successfully fabricated for the detection of various heavy metal ions by employing fluorescent gold nanoclusters (AuNCs) as nanoprobes, serious cross-interference often occurs when these ions coexist in samples, which results in glaring errors in quantification. In this study, glutathione-protected AuNCs (GSH-AuNCs) were synthesized and found to respond to both Cu2+ and Hg2+ via fluorescence suppression. Intriguingly, addition of Ag+ to GSH-AuNCs could completely inhibit the quenching effect of Hg2+ while not affecting the Cu2+-mediated quenching process. Ag+ can combine with Au+ on the surface of AuNCs to form a strong Ag+-Au+ metallic bond, which disrupts the interaction between Hg2+ and Au+ and thus eliminates the corresponding quenching effect. Based on this phenomenon, a simple sensing approach for highly selective and sensitive detection of Cu2+ in aqueous solution was developed using the GSH-AuNC/Ag+ complex as a fluorescent turn-off nanoprobe. The proposed method exhibited good linearity in the concentration range 0.02–10 μM with a limit of detection of 12 nM. This assay was demonstrated to be suitable for determination of Cu2+ in real water samples even in the presence of Hg2+, showing great promise as a tool for assessment of environmental security and drinking water quality.

Human serum is a huge bioinformatics database of human physiological and pathological state, many proteins/peptides among which can serve as biomarkers for monitoring human's health condition, thereby being worth exploring. The simple and fast capture of biomarkers from human serum is the first key step to realize their accurate detection. In this work, we developed the aptamer functionalized magnetic metal organic framework nanoprobe, and furtherly combined with mass spectrometry technology to establish an efficient method of identifying biomarkers. Taking insulin as example of biomarker in human serum, we developed sulfhydryl human insulin aptamer functionalized magnetic metal organic framework (denoted as Mag MOF@Au@HIA) through the post-synthetic modification of MIL-101(Cr)–NH2 for testing the applicability of the established method. Depending on the strong magnetic responsiveness and high specific area as well as high-loaded human insulin aptamers, the limit of detection of insulin was down to 1 ng/mL and 2 ng/mL in the standard insulin solution and human serum, respectively. Moreover, a good linear relationship (R2 = 0.998) was obtained by using standard insulin solution with concentration range from 100 ng/mL to 5 ng/mL, based on which the capture recovery of insulin with Mag MOF@Au@HIA from human serum was demonstrated to be excellent. All of the results indicate that the aptamer-functionalized magnetic metal organic framework is a promising nanoprobe for biomarkers capture in human serum.

In this paper, a surface-enhanced fluorescent (SEF) substrate with Ag nanostructures was synthesized by magnetron sputtering, which exhibits simple, fast, inexpensive, environmentally friendly properties, and can also be in a bulk production. The localized surface plasmon resonance (LSPR) generated by Ag-decorated dragonfly wings (DWs) substrate plays a huge role in fluorescence enhancement. The common rhodamine 6G (R6G) was used as the fluorescent dye, and a substrate having high fluorescence intensity was selected. Besides, the morphological and optical properties of the different substrates were characterized, and their enhancement factor (EF) were also calculated in order to more accurately quantify the enhancement of fluorescence. Meanwhile, using finite-difference time-domain (FDTD) method to simulate the local surface electromagnetic field of Ag nanostructure is helpful to further analyze the “hot spots” distribution of the substrate. Experimental results show that the substrate has excellent stability, reproducibility and reusability, which will have great application prospects in many fields such as life science, environmental testing, optoelectronic devices.

Here, a label-free fluorescent sensor was developed for detection Fe (III) by utilizing the quenching effect of Fe (III) on the fluorescence of the hydroxyl functionalized metal-organic framework MIL-53(Fe)-(OH)2, which was synthesized by using a one-step solvothermal method. The specific binding interaction between Fe (III) and hydroxyl facilitated the absorption of free Fe (III) to MIL-53(Fe)-(OH)2, which leads to rapid fluorescent intensity quenching effect. The potential quenching mechanism was proved to be the photo-induced electron transfer (PET) from electron-rich ligands of MIL-53(Fe)-(OH)2 to the half-filled 3d orbitals of free Fe (III) in the sample solution. For in-field applications, the fluorescence signal was detected rapidly by using a homemade 3D-printed, portable, and low-cost smartphone sensor. A commercial 365 nm UV LED light was adopted as the excitation light source, while the camera in a smartphone was utilized as the optical detector. The fluorescent signals obtained by using the smartphone sensor were in a good agreement with those obtained from a commercial microplate reader. Under the optimal assay conditions, the linear detection range of Fe (III) was 5.0–200 μM, and the limit of detection is 1.7 μM. This result is compatible with the commercial microplate reader. The developed method was successfully adopted to detect Fe (III) in human serum and environmental water samples with acceptable recovery values of 90–108.5%. The portable, low-cost, fast-response, user-friendly and sensitive fluorescent protocol based on a self-quenching fluorescent nanoprobe can be conducted at home or anywhere else without sophisticated instruments, showing a great application potential in clinical diagnosis, on-site environmental monitoring and healthcare at home.

A novel fluorescent nanocomposite based on 6-amino-2-mercaptobenzothiazole (AMBT) was synthesized, characterized, and used as high-performance probe for detection of trace amounts of Fe3+ ions in water. The prepared AMBT-based ligand was grafted on Fe3O4@SiO2 nanocomposites, which provide both high surface area for hosting the ligand and easy magnetic removal of the nanoprobe from water. The prepared nanoprobe was characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermal gravimetric analysis, and vibrating sample magnetometer. Moreover, the designed nanocomposite showed spectroscopic colorimetric properties against low concentrations of Fe3+ ions in water. The detection limits of the probe for fluorometric and colorimetric detection of Fe3+ were 16.0 × 10−9 M and 0.75 × 10−6 M, respectively. Finally, the performance of the probe was tested in a natural water sample for detecting trace amounts of Fe3+. The theoretical calculations of the molecular structure for the designed organic ligand and its interaction with different ions confirmed strong binding energy of iron atom with thiol group of the ligand.

β-Glucuronidase (β-GCU) is closely related to the occurrence of multiple diseases, and it has been applied as a biomarker and therapeutic target in clinical diagnosis. However, reliable methods with high selectivity and sensitivity for monitoring β-GCU are still lacked. Herein, we designed a novel fluorescent nanoprobe, rhodamine B encapsulated MOF-5 (RhB@MOF-5) for the first time, to detect β-GCU through the synergistic effect of inner filter effect (IFE) and static quenching effect (SQE) by employing 4-nitrophenyl-β-D-glucuronide (PNPG) as the substrate. After encapsulating into MOF-5, the fluorescence emission of RhB at 550 nm excited by 320 nm was greatly enhanced. The major overlap between the fluorescence excitation spectrum of RhB@MOF-5 (about 320 nm) and the ultraviolet absorption spectrum of PNPG (about 310 nm) lead to PNPG being a good IFE absorber in this sensing system. Under the optimized conditions, the excitation spectrum of the RhB@MOF-5 could be absorbed by PNPG, resulting in the dramatically decrease of fluorescence emission. After adding β-GCU into the system, the substrate of PNPG would be enzymatic hydrolyzed to p-nitrophenol (PNP) and glucose, then the IFE disappearance and the fluorescence recovered. The current sensing platform was interference-free and exhibited a broad linearity relationship for β-GCU range of 0.1–10 U L−1 (R2 = 0.9957) with a limit of detection as low as 0.03 U L−1, which was reduced by more than one orders compared with the reported methods. Moreover, the encapsulation of dyes using porous nanoparticles to achieve some tailor-made characteristics will enrich experimental design inspiration.

Development of luminescent probes for rapid and effective discrimination and detection of cancer cells has the potential to address the current challenges in early diagnosis and treatment monitoring of cancer diseases. In this work, we report the preparation of a unique folic acid (FA)-functionalized dual-emissive nanoprobe, CTMR@BHHBCB-Eu-FA , for steady-state and time-gated luminescence “double-check” imaging of cancer cells. The nanoprobe was engineered by covalently doping two luminescent dyes, 5-carboxytetramethylrhodamine (CTMR) and BHHBCB-Eu 3+ , in core and shell of silica nanoparticles, followed by surface modification of the nanoparticles with FA, a cancer cell-targeting molecule. As-prepared nanoprobe is monodisperse and highly stable in buffer displaying two strong emissions, short-lived emission from CTMR at 584 nm and long-lived emission from BHHBCB-Eu 3+ at 612 nm. The nanoprobe is biocompatible, and can specifically recognize folate receptor (FR)-overexpressed cancer cells through the FA-FR binding interaction. Using the nanoprobe, the “double-check” imaging of HeLa cells was successfully achieved at steady-state and time-gated luminescence modes, indicating the capability of the nanoprobe for cancer cell imaging.

A novel nanosensor is developed for selective and highly sensitive detection of phytic acid (PA) based on small-sized conjugated polyelectrolyte dots (Pdots) fabricated from a new conjugated polymer (P1) by a modified reprecipitation method. P1 featuring a π-delocalized backbone bearing meta-substituted pyridyl groups can be endowed with enhanced flexibility and hence is beneficial for the synthesis of ultrasmall Pdots (i.e. Pdot-1, ∼3.8 nm in average diameter) as well as for the binding of Fe3+, thus leading to the obvious fluorescence quenching of Pdot-1 (∼444 nm) in the presence of Fe3+ via an electron transfer (ET) process. In addition, phytic acid with six phosphate groups exhibits strong chelating ability. When phytic acid is added, phytic acid readily binds to Fe3+ and the fluorescence of Pdot-1 around 444 nm can be recovered, rendering the supersensitive and selective sensing of PA. Under the optimum conditions, this ultra-small Pdot-based nanoprobe favors the fluorescent determination of PA with the detection limit as low as 10 nM. Particularly, Pdot-1 with bright blue fluorescence exhibits low cytotoxicity. Furthermore, the small-sized and biocompatible Pdot-1 can be applied to the sensitive fluorescence assay for PA in cell extracts and the efficient imaging of PA in live cells.

Carbon dots (CDs) were prepared from gallic acid and polyene polyamine (PEPA) via a solvothermal method. The as-synthesized CDs are well monodispersed in water with a uniform size (20–30 nm). CDs exhibit excitation wavelength–dependent and concentration-dependent optical behaviors and possess excellent hydrophilicity and good biocompatibility. More importantly, the as-synthesized CDs could act as an excellent nanoprobe for sensing Fe3+ in living cells.

Aggregation-induced emission luminogens (AIEgens) provide a new approach to address the aggregation-induced quenching (ACQ) defect prevalent in traditional fluorescent dyes. Since there are only two dispersion forms of single molecule (monomer state, weak fluorescence) and aggregates (multimer state, strong fluorescence) in aqueous medium, most of the reported AIEgens exhibit a single emission band and therefore cannot be used for dual-channel fluorescence imaging in living cells. In this work, the “monomer-dimer-multimer” dispersion mechanism was innovatively introduced into the design of dual-emission AIEgens. Under the guidance of this concept, two cyanovinyl-pyrene dual-emission AIEgens with twisted molecular configuration have been readily synthesized and studied by theoretical calculations, UV–visible absorption, steady-state fluorescence, time-resolved fluorescence, dynamic laser scanning (DLS) and laser confocal imaging. These AIEgens emit weak fluorescence in monomer state due to intramolecular C C rotation. With gradual aggregation, they form dimer state to emit blue fluorescence centered at 460 nm, and then convert into multimer state to emit red fluorescence around 570 nm, simultaneously exhibiting AIE and dual-emission characteristics. They also have excellent photostability, good membrane permeability and low cytotoxicity. Confocal imaging tests demonstrate that AIEgens composed of cyanovinyl-pyrene and benzimidazole moieties is available for dual-channel imaging in Hela cells and macrophages cells, and shows great potential in designing ratiometric nanoprobe. Our design mechanism will provide a versatile platform for the development of dual-emission AIEgens.

In this work, simple raw materials and reaction conditions were used to synthesize a versatile nanoprobe using a one-step method. Graphene quantum dot (GQD) and gold chloride were mixed and irradiated with ultra-violet (UV) radiation for 1 min. Then, the gold nanosphere cluster with the diameter of 50 nm and coated using GQD was formed using a facile one-step approach. GQD played the roles of reducing agent, stabilizer and drug carrier instead of a harmful reducing agent or stabilizer. The nanoprobe had good dispersion, stability, excellent photoacoustic imaging (PAI) and computed tomography (CT) imaging performance, low cytotoxicity and photothermal conversion efficiency of up to 51.31%. The results for cell and animal experiments showed that targeted PAI/CT imaging of tumor after modification of folic acid (FA) could be obtained using the probe. Meanwhile, after the adsorption of doxorubicin, the chemo-photothermal combined therapy for tumor could be carried out through controlled drug release from GQD under heated and acidic environment of tumor. Additionally, the treatment effect was significantly superior to single modes. The body weight, Hematoxylin and Eeosin (H&E) staining of main organs and blood biochemical indicators showed that the probe had good biological safety after injection. The current work proposes a new dual-mode bio-imaging and chemo-photothermal combined therapy nanoprobe, which presents good application prospect for tumor theragnostic.

Glycosylation and phosphorylation are two important mechanisms in organism, both of which can finely regulate protein function respectively or simultaneously. Functional nanoprobes with various reversible interactions of aiming at glycan or phosphate group have been advanced dramatically, however, the comprehensive analysis towards them is largely restricted by the challenge to capture glycopeptides and phosphopeptides at the same time from complex samples due to the limitation of nanoprobe functionalization. Here, we fabricate a promising nanoprobe using the hydrophilic l-cysteine and titanium ions to enhance the phosphopeptides capture, meanwhile, realize the glycopeptides capture. We test the performance of the promising nanoprobe, showing that it is not only equipped with good unbiased ability in glycopeptides capture with high sensitivity and selectivity, but also highly effective for phosphopeptides capture. More importantly, the promising nanoprobe enables the simultaneous capture and analysis of glycosylated and phosphorylated peptides from mouse brain, as well as human eye lens of normal and cataract. The identification of glycosylated and phosphorylated sites within normal and cataract reflects their differential expression and offers an excellent insight to glycosylation/phosphorylation-related human eye diseases, indicating its great potential in glycoproteomics and phosphoproteomics researches.

A novel nitrogen and sulfur co-doped carbon dots (NS-CDs)-H2O2 chemiluminescence (CL) system was developed to detect carcinoembryonic antigen (CEA) by taking advantage of dual-signal amplification of functional Au@Ag nanoparticles (NPs) nanoprobes. Horseradish peroxidase (HRP) and the complementary DNA were co-immobilized onto Au@Ag NPs surface to shape the functional nanoprobes (HRP-Au@Ag-cDNA) for signal amplification. In this proposal, HRP-Au@Ag-cDNA was specifically hybridized with CEA aptamer-functionalized magnetic beads to form the double-strand hybridization nanocomposites (HRP-Au@Ag-dsDNA-MB). Upon the addition of CEA, the CEA aptamer preferred to bind with CEA instead of double-strand hybridization interaction, thus HRP-Au@Ag-dsDNA-MB was dehybridized and the HRP-Au@Ag-cDNA nanoprobe was released. The synergistic catalytic effects of HRP and Au @Ag NPs endow the nanoprobe producing a dual CL signal amplification in the NS-CDs-H2O2 CL system. The CL intensity of the developed strategy enhanced with CEA concentration increasing in the range of 0.3–80 ng mL−1. Benefiting from the synergistic effect, a detection limit as low as 94 pg mL−1 was obtained. Moreover, successful application of this CL sensing platform was achieved for the determination of CEA in human serum samples, demonstrating the promising prospect in the early tumor warning and therapeutic monitoring.

Ascorbic acid (AA) is an essential vitamin and plays an irreplaceable role in humans’ daily life. Therefore, it is of profound significance to develop effective strategies for AA sensing. Herein, a novel bi-functional sensing strategy was developed by using carbon dots (CDs) and MnO2 nanosheet as the fluorometric/magnetic signal source. When AA was absence, the fluorescence of CDs was quenched by MnO2 nanosheet due to the inner filter effect. Neither the fluorescence nor magnetic signal of the nanoprobe can be detected. In the presence of AA, a redox reaction occurred between MnO2 nanosheet and AA resulting in the generation of magnetic resonance imaging (MRI) response Mn2+ and decomposing of MnO2 nanosheet structure, thus leading to the recovery of CDs fluorescence. The detection limit of the AA was determined to be 2.89 μM with a linear range of 0–80 μM in fluorescence mode, and detection limit of 0.776 μM with a linear range of 0–80 μM in MRI mode when used transverse relaxation rate as signal. Furthermore, the developed fluorometric/magnetic bi-functional nanoprobe showed good biocompatibility, high response rate, high selectivity towards AA and could be used to analyses AA in real samples. Moreover, in vivo imaging of AA in mice was achieved in magnetic mode. The fluorometric/magnetic bi-function sensor for AA detection was introduced, which provided a novel strategy for sensor design based on CDs.

Here, a pH-responsive ZnO nanoprobe mediated DNAzyme signal amplification strategy was proposed for sensitive detection and live cell imaging of multiple microRNAs. The nanoprobe including ZnO nanoparticles (ZnO NPs) core as carrier and cofactor provider and polydopamine shell for adsorption the functional hairpin DNAs was designed. When nanoprobe entered the cell through endocytosis, the acidic environment of the cell could decompose the ZnO NPs core to release the functional hairpin DNAs and Zn2+. The Zn2+ could act as cofactor for the DNAzyme cleavage amplification reaction, avoiding additional cell delivery processes. The recognition hairpin DNAs (H1 and H3) recognized microRNA and exposed the DNAzyme. The DNAzyme cleaved cyclically the reporter hairpin DNAs (H2 and H4), producing enhanced fluorescent signal for miR-21 and miR-373 detection with the detection limit of 54 pM and 38 pM, respectively. Expression levels of miR-21 in Hela, HepG-2 and L02 cells were differentiated. Furthermore, simultaneous imaging of miR-21 and miR-373 in same living cells was achieved. These results indicated this strategy could have a potential application in microRNAs assays for the accurate diagnosis and therapy of cancer.

Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS2/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS2 nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS2@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS2@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS2@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS2@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm2). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.

Ammonia concentration together with pH values are important and closely linked indexes for aqueous systems. Rapid on-site determination of ammonia or pH is of great significance to environmental monitoring. In this work, a pH-switchable nanoprobe based on biomass carbon dots (CDs) is developed using a smartphone as a simple and handy instrument. The CDs demonstrate sensitive pH response in wide linear ranges of 6.1–13.6, and 2.0–13.6 with colorimetric and fluorescent channels, respectively. It is the pH-induced aggregation that governs the color and fluorescence switch. With the pH evolution caused by the dissolution of ammonia, the smartphone-integrated nanoprobe is applied to ammonia detection with a broad range of 0.5–300 mM. Moreover, the headspace single drop microextraction strategy can concentrate ammonia from matrix, offering a remarkably high selectivity for ammonia determination. Finally, the practical applications of this method for ammonia analysis obtained satisfactory results.

Due to severely overlapping emission and or/ excitation spectra of polycyclic aromatic hydrocarbons (PAHs), the specifically recognizing PAHs by the fluorescent technique is still a challenge. Here, synthesized Ag@SiO2 nanoparticles with 40 ± 4 nm Ag core and 7 ± 1 nm SiO2 shell performing as a nanoprobe could selectively recognize 2-aminoanthracene (2-AA) via metal-enhanced fluorescence (MEF) within 2 min. The sensing mechanism was based on the facts: (1) there was a perfect spectral overlap between the local surface plasmon resonance (LSPR) peak of Ag@SiO2 and the absorptive peak of 2-AA, and (2) 2-AA could interact with Ag@SiO2 nanoparticles through hydrogen bonds between –NH2 in 2-AA and –OH in SiO2 shell. As a result, with Ag@SiO2 nanoparticles as a nanoprobe, a fluorescent assay for detecting 2-AA was developed with a linear range from 1 nM to 800 nM, which exhibited an excellent selectivity over possible PAHs, dyes and metal ions. The detection limit was 1 nM. Finally, the developed assay was applied to analyse 2-AA in industrial wastewater samples, which were highly consistent with that of high performance liquid chromatography (HPLC). This study presents a feasible assay for detecting 2-AA for environmental monitoring and toxic evaluating.

The core-shell SERS nanoprobe combined with adhesive tape was used to recognize the latent fingerprints on the surface of the object, which provides an effective solution for the imaging of latent fingerprints on the surface of large immobile or curved objects. First, the Au@pNTP@SiO2 SERS probes modified by aptamers specific to lysozyme were prepared, and characterized by TEM/EDS, and its SERS effects were also tested. Then the probe was incubated with the aged-latent fingerprints on the surface of different objects. Afterwards, the dried latent fingerprint with modified SERS probes was transferred to the adhesive tape and imaged under the confocal Raman microscope. The results showed that the size distribution of the core-shell SERS probe was uniform, which was mostly concentrated in 60 nm, leading to excellent stability and dispersity. The SERS probe also had strong SERS intensity and reproducibility with the characteristic peaks at 723, 855, 1081, 1343 and 1572 cm−1, which were consistent with the previous reports. When applying such SERS probe into the tape-transferred latent fingerprint's imaging, not only the primary structure (pattern) but also the secondary structure (forking and ring points) and the third-level structure of fingerprint (sweat pore) could be clearly observed. The successful development of the SERS imaging of transferred latent fingerprint on adhesive tapes combined with the aptamer-functionalized SERS probe provides an effective method for recognizing latent fingerprints in forensic science, which also has the potential applications in the other areas such as food safety and public safety testing.

Simply obtained by the oxidation of levodopa in alkaline media, polylevodopa nanoparticles are able to quench the fluorescence emission of CdTe quantum dots (QDs) via energy transfer mechanism. The extent of this quenching can be exploited for the quantification of levodopa, as an important therapeutic agent in the treatment of Parkinson's disease. However, to effectively improve the detection performance, in this study, we have designed a ratiometric probe by making use of variations in both the emission of QDs and the intrinsic emission of polylevodopa nanoparticles. The enhanced sensitivity, in particular, arose from the measurement of the ratio of fluorescence intensities at two different wavelengths, by which the resulting signal was totally analyte-dependent and free from environmental effects. The built-in self-calibration in this ratiometric approach led to a remarkable detection limit of 18.3 nmol L−1, without interruption from possible interferences. The proposed ratiometric nanoprobe not only proved to be highly selective, but also showed to be capable of successively detecting levodopa in complex biological fluids such as plasma, in which possible interferences are usually likely to affect the detection results.

A label-free and turn-off fluorescence method for detecting cytochrome c (Cyt c) was developed using enhanced DNA-templated silver nanoclusters (DNA-AgNCs@tween 80) as a novel fluorescence-enhancing nanoprobe. Cyt c-induced electron transfer between Cyt c and DNA-AgNCs results in a significant fluorescence quenching effect of DNA-AgNCs. The coated tween 80 around DNA-AgNCs particles significantly causes fluorescence signal enhancement in the solution. Meanwhile, the efficiency of fluorescence quenching by Cyt c increases substantially by adding 0.1% tween 80 (final volume concentration) into the detection system. Based on these findings, a simple method with the detection limit of 0.8 nM was established for Cyt c based on tween 80 enhanced DNA-AgNCs. A good linear relationship between the fluorescent intensity and the concentration of Cyt c ranging from 0.8 nM to 20,000 nM (R2 = 0.9910) was obtained. Consequently, the method was applied to monitor the Cyt c variation in HCT-116 and BGC-823 tumor cell culture medium after being treated with doxorubicin (DOX)and two kinds of natural compounds (J5 and S6, extracted from plants Abacopteris Penangiana and Swertia punicea Hemsl, respectively). The results indicate that the level of Cyt c in cell culture medium decreases according to the presence of DOX, J5 and S6. The reliability of the result was further confirmed by using cell viability assay and flow cytometry for apoptosis analysis (FACS). From these data, it can be concluded that this groundbreaking nanoprobe with high sensitivity, great simplicity and good biocompatibility boosts a promising outlook for exploring the molecular mechanisms of apoptosis regulation and nature drugs screening.

Fluorescent probes conjugated to peptide or antibody directing groups, which exhibit high signal to background ratios, have been widely used to image tumors and monitor their growth. A photo-triggered cycloaddition reaction between the arginine-glycine-aspartic acid -N-ɛ-acryllysine (RGD-Acrk) peptides and the tetrazole compounds bound to the surface of biodegradable mesoporous silica nanoparticles (bMSN) has been used to construct a fluorescent nanoprobe (bMSN@T2-RGD-Acrk), which showed fluorescent emission at 550 nm and could selectively image the 4T1 cells and breast cancer. This means that the bMSN@T2-RGD-Acrk nanoprobe made by photo-triggered conjugation approach is a promising fluorescent imaging agent for visualizing tumors. Thus, the photo-triggered one-spot reaction can give a stable crosslinker in a biocompatible manner for bioconjugation with nanoparticles and produce a fluorescent group that is suitable for imaging in vivo.