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A sensitive biosensor that can be used for the determination of matrix metalloproteinase 2 (MMP-2) was proposed. The biosensor was developed by using an excellent self-enhanced nanocomposites as an illuminant and a peptide as a recognition element. For the electrostatic attraction between Ru(bpy)32+ and nitrogen-doped graphene quantum dots (NGQDs), the self-enhanced electrochemiluminescence (ECL) nanocomposites of NGQDs-Ru(bpy)32+-doped silica nanoparticles (NGQDs-Ru@SiO2) were synthesized through a simple sol-gel process. Then, a specific peptide (labeled sulfhydryl) was combined with the self-enhanced ECL nanocomposites (carboxyl in NGQDs) via acylation reaction to obtain the peptide-NGQDs-Ru@SiO2 nanoprobe, which was fabricated onto the gold electrode surface via Au–S bond. The peptide of the ECL nanoprobe was exposed to cleavage in the presence of MMP-2, which caused the signal substance to move farther away from the electrode, leading to a decrease of the ECL signal. The proposed NGQDs-Ru@SiO2-labeled peptide ECL biosensor displayed a lower detection limit of 6.5 pg mL−1 than those of reported ECL methods. The proposed biosensor provided an outlook for future applications in other disease-associated biomarkers.

Sensitivity and credibility detecting histamine (HA) as an important neurotransmitter in biofluids is of importance in analytical science and physiology. Surface-enhanced Raman spectroscopy (SERS) is able to realize the high sensitivity with single molecules level, but providing the high sensitivity for HA with a small cross section remains a challenge. Here we develop the metal complex-based SERS nanoprobe nitrilotriacetic acid-Ni2+ (NTA-Ni2+) combined with self-assemble Au NPs active substrates for sensitive detection of HA. The NTA-Ni2+ can capture the HA molecules close to Au NPs substrates and then amplify the Raman signals of HA owing to the formation of a complex of NTA-Ni2+-HA. The self-assemble Au film through the evaporation-driven method can provide the high-density hot spots substrate with high stability and reproducibility. The NTA-Ni2+ decorated Au NPs as nanoprobe responds to HA with 1 μM level of sensitivity. More importantly, the developed SERS nanoprobe composing of NTA-Ni2+ and self-assemble Au NPs can be utilized to detect and monitor the HA spiked into serum, indicating the potential prospect in analysis of HA in complex specimen.

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.

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.

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.

A novel method based on surface-enhanced Raman scattering (SERS) was developed to estimate the reducing capacity of phenolic acids by using self-assembled three-dimensionally (3D) ordered gold nanoparticles (GNPs) precursor composite (SiO2/GNPs) arrays as nanoprobes. In the present work, the 3D ordered SiO2/GNPs arrays immersed in the growth solution containing different phenolic acids, the SiO2/GNPs were enlarged to varying degrees. Phenolic acids with one or more phenolic hydroxyl groups served as reductants for the growth of GNPs. The enlargement conditions varied with the different reducing capacity of phenolic acids, exhibiting specific morphologies differ from the complete gold nanoshells (GNSs). Consequently, the UV–vis spectra and SERS spectra for the phenolic acid-treated SiO2/GNPs arrays were gradually changed. The change of the intensities of the SERS spectra correlated well with phenolic acids concentration which indicated that this SiO2/GNPs array is a suitable SERS nanoprobe for phenolic acids. Results showed that the higher reducing capacity of phenolic acid, the stronger SERS of the enlarged GNSs. Thus, the SERS results could be used to evaluate the antioxidant capacity of phenolic acids by utilizing 3D ordered SiO2/GNPs arrays as nanoprobes. The results also indicated that the reducing capacity of these three phenolic acids was in the order gallic acid > syringic acid > vanillic acid. The detection ranges of vanillic acid, syringic acid and gallic acid were 10–250 µM, 10–110 µM and 5–55 µM, respectively.

In this work, a core-shell structured upconversion nanoparticles@zeolitic imidazolate frameworks (ZIF-8) fluorescent nanoprobe (NaErF4:Tm@SiO2@ZIF-8) has been designed for the detection of gallic acid (GA). The mechanism is according to the 3, 3′, 5, 5′-tetramethylbenzidine (TMB) can be oxidized to oxidized TMB (oxTMB) by Ag+. Under 980 nm laser excitation, NaErF4:Tm@SiO2@ZIF-8 can emit red light at 652 nm, which have a good overlap with the absorption spectra of oxTMB, resulting in the fluorescence quenching at 652 nm. Continually adding GA into the above solution, oxTMB will restore to TMB, and the fluorescence intensity at 652 nm gradually recovers, which can realize the detection towards GA. The linear detection range of GA is from 0 to 30 μM, and the limit of detection (LOD) of GA is 0.35 μM. The ZIF-8 can largely enhance the sensitivity of the nanoprobe, due to the physical absorption and the electrostatic attraction between ZIF-8 and the oxTMB. More importantly, this is the first time to realize the detection of GA with high sensitivity by using upconversion fluorescence. Besides, we have realized the analysis of GA in real samples, which certify the feasible of the nanoprobe in potential applications.

Photodynamic therapy (PDT) received great attention in cancer therapy due to the advantages of negligible drug resistance, low side effects, and minimal invasiveness. Development of theranostic nanoprobes with specific imaging-guided PDT is of great significance in the field. Herein we report the fabrication of a novel theranostic nanoprobe porphyrin/G-quadruplex conjugated gold/persistent luminescence nanocomposites for imaging-guided PDT. The developed nanoprobe contains NIR-emitting persistent luminescent nanoparticles (PLNP) as the core for autofluorescence-free bioimaging and Au coating on PLNP for facile subsequent DNA conjugation. The DNA sequence is designed to contain G-rich AS1411 aptamer for recognizing the over-expressed cellular nucleolin of cancer cell and forming a G-quadruplex structure to combine with tetrakis (4-carboxyphenyl) porphyrin (TCPP) to realize PDT. The AS1411 aptamer-contained DNA conjugated Au-coated PLNP is rapidly prepared via a freezing method with high content of DNA and good aqueous stability. Meanwhile, TCPP is easily loaded into the G-quadruplex structure formed from G-rich AS1411 aptamer on the surface of Au/PLNP in presence of K+. The theranostic nanoprobe gives integrated merits of PLNP for autofluorescence-free bioimging, TCPP for PDT and AS1411 aptamer-contained DNA for specific binding to cancer cells. This work provides a new specially designed imaging-guided PDT nanoplatform for theranostics.

The anti-tumor effects of metformin hydrochloride (MH), an initial pharmacologic agent for type 2 diabetes, were reexamined by surface-enhanced Raman scattering (SERS) spectroscopy. A SERS immuno-tag fabricated by decorating silver nanoparticles (AgNPs) with a specific antibody was employed to trace the dynamic expression of the tumor metastasis-related N-cadherin. With the MH action, the N-cadherin expression on the cell membranes decreases, proving that MH has a pharmacological effect on prohibiting cancer cell metastasis. Another AgNP-based nucleus targeting nanoprobe was adopted to culture with the MH acted cells, which can help the label-free SERS collection of the cell nuclei to explore the MH influences on intranuclear genes and proteins. By analyzing the intranuclear SERS spectra, the find is that MH has impacts on the transcription and translation of genes, thus regulates the expression of tumor metastasis-related proteins (N-cadherins). This study presents a proof-of-concept for MH as a potential drug for diabetes patients associated with tumors. The developed plasmonic immune analytical platform can be extended to assess other substances of the cell membrane and applicable for the SERS-based screening of membrane receptor-related drugs at the cellular level.

A composite fluorescent nanoprobe based on metal enhanced fluorescence (MEF) effect of gelatin-coated silver nanoparticles (AgNPs@gel) was developed for selective and sensitive detection of dopamine (DA). The characteristic fluorescence of Tb(III) was using as the detection signal and AgNPs@gel served as substrates of the MEF. Gelatin with rich amine and carboxylic groups was used not only as a co-ligand of Tb(III) complex, but also as a bridging substance and a spacing material for improving the MEF of AgNPs@gel on the intrinsic luminescent intensity of Tb(III). Under the optimal conditions, the increment of the fluorescence intensity (measured at 307/544 nm as excitation/emission wavelength) of the system increased linearly with the concentration of DA in the range of 0.80–100 nM (R2 = 0.9937) and 100–1000 nM (R2 = 0.9978). The fluorescent probe greatly improved Tb(III) luminescence, which paved the way for sensitive detection with a low detection limit of 0.54 nM. It also showed good selectivity among other neurotransmitters. This work was successfully applied to the determination of DA in human serum samples with recoveries ranging from 99.8 to 102.2%. We believe that the Tb(III)-DA-AgNPs@gel composite fluorescent probe can be developed as a new approach for DA detection.

In this study, a novel, simple and sensitive ratiometric fluorescence method is presented for the detection of very low quantities of the carbaryl in Iranian apple using cadmium telluride quantum dots (CdTe QDs) nanoprobe. The principle of the proposed strategy relies on the rapid hydrolysis of the carbaryl under an alkaline condition and production of the 1-naphthol with a blue emission at 470 nm. Besides, using the CdTe QDs with a yellow emission at 580 nm, as a reference, improves the visual tracking of carbaryl through changes in color tonality. The herein described methodology is applied for enzyme-free visual detection of carbaryl with satisfactory results in the presence of other common pesticides in Iranian apple sample. Additionally, the calculated limit of detection (LOD) of 0.12 ng mL−1 for carbaryl is much lower than the maximum residue limits of carbaryl warned value reported by the European Union and United States pesticides database, which is so promising for carbaryl sensing in the monitoring of fruits. Furthermore, the ability of the proposed method for the detection of carbaryl residues in Iranian apple was confirmed by the high-performance liquid chromatography (HPLC) method as a standard method through statistical analysis. This fast and highly sensitive naked-eye ratiometric sensor may hold great promise to provide the technical support for the rapid and valid detection of other targets in food safety fields.

This work demonstrates a simple, cost effective and ultrasensitive detection of ethyl parathion, an organophosphorus (OPs) pesticide, using enzyme based fluorometric sensing strategy by employing bimetallic BSA@AuAg nanoclusters (NC). The sensing assay is based on the "quenched off" state of bimetallic NC with the addition of Cu2+ ions that can be "switched on" due to generation of thiocholine (TCh), a catalytic product of enzymatic reaction of acetylthiocholine (ATCh) using acetylcholinesterase (AChE) enzyme. The generated TCh preferably seize Cu2+ ions from BSA@AuAg NC-Cu2+ ensemble and recovered the fluorescence of BSA@AuAg NC. The presence of ethyl parathion can be monitored optically due to its inhibitory action towards AChE enzyme leading to suppression of thiocholine (TCh) formation and subsequently decreases TCh-Cu2+ interaction that ultimately retrieved quenched off state of bimetallic NC. The synthesized biosensor is appropriate for the ultrasensitive sensing of ethyl parathion in pM range, exhibiting 2.40 pM as lowest limit of detection (LOD) which is the least known so far. Further, the real sample analysis adds on for the appropriateness of the synthesized nanoprobe by depicting excellent reproducibility and robustness. The designed assay proved its specificity towards pesticides in general and ethyl parathion in particular when employed with other commonly used non-OPs pesticides.

Bimodal photoluminescence-magnetic resonance (MR) imaging technique has attracted tremendous attention due to its great potential in biomedical researches and clinical practices. Herein a novel multifunctional magnetoluminescent nanocomposite, FA-Gd-Tb@SiO2, was found to serve as an effective probe for bimodal time-gated luminescence/MR imaging of cancer cells in vitro and in vivo. The nanoprobe was designed by integrating a luminescent Tb3+ complex, a Gd(III)-based contrast agent and a tumor-targeting molecule, folic acid (FA), into a silica nanoparticle. The integration of these functional moieties allows the nanoprobe to be employed for specific imaging of cancer cells with background-free TGL and non-invasive MR imaging modes. In addition, the optical and magnetic properties were dramatically improved after implicating the newly synthesized nanoarchitecture. In vitro cellular TGL imaging demonstrated that the FA-Gd-Tb@SiO2 nanoprobe could recognize and accumulate in cancer cells overexpressing FA receptor. Furthermore, in vivo study revealed that the as-prepared nanoprobe was able to effectively enhance T1-weighted MR contrast and TGL intensity in tumor tissue, which might contribute to the precise detection and tracing of cancer cells, as well as diagnosis and therapy of tumor in clinical.

The expression levels of glycans on the surfaces of cancer and normal cells show different, however, this difference is not noticeable enough to distinguish them directly. So, herein, based on the targeted molecular recognition of the glycans on cell surfaces by 4-mercaptophenyl boronic acid (MPBA), a novel surface-enhanced Raman scattering (SERS) nanoprobe (glucose-MPBA@AgNPs) was prepared by inducing controllable assembly of MPBA decorated Ag nanoparticles (MPBA@AgNPs) in a certain level via the bridge of glucose to amplify such a limited difference in SERS measurements. On the basis of the aggregation-induced 3D SERS hot spot effect, this multi-particle nanoprobe possesses over 10 times stronger SERS enhancement ability than the individual MPBA@AgNPs. As the different sialic acid (SA) expression on the surfaces of cancer and normal cells led to the different accumulation of glucose-MPBA@AgNPs, the results we obtained (mean intensities recorded from five cells) indicate the SA amounts on two kinds of cells can provide 5-7 times signal contrast grade in SERS band intensities (P < 0.001). Compared with the monodispersed nanoprobe, our developed nanoprobe amplifies the SA expression difference on cell surfaces and supports high sensitivity for cancer cell recognition, which might be useful in providing highly effective recognition of the edges of tumor tissues in clinic field.

A fluorescent nanoprobe based on nitrogen-doped carbon dots (N-CDs) with green fluorescent emission have been fabricated through a facile one-step hydrothermal treatment using catechol and triethylene tetramine as precursors. The obtained N-CDs with excellent luminescent properties and superior biocompatibility have been applied for the development of a bifunctional sensor for the detection of Fe3+ and ascorbic acid (AA). Fe3+ that are tightly chelating the surface of N-CDs can induce fluorescence (FL) quenching of N-CDs through photo-induced electron transfer (PET). Meanwhile, the addition of AA serves to shelter the CDs effectively from being quenched by Fe3+ due to AA, as an antioxidant, enable easy-conversion of Fe3+ to reduced states (i.e. Fe3+ and Fe2+). The N-CDs are used as a facile and label-free “on-off-on” fluorescent nanoprobe for the determination of Fe3+ and AA with detection limits of 58.82 nM and 0.236 µM with the corresponding linear ranges of 25–200 µM and 25–300 µM, respectively. According to this phenomenon, an “AND” logic gate based on the novel N-CDs has been constructed. As-prepared N-CDs with negligible toxicity and perfect biocompatibility were expanded for cellular imaging and sensing Fe3+ and AA in living cell, which enlarges the application range of the N-CDs. Most importantly, the as-constructed fluorescent sensing system was successfully applied to detection of Fe3+ in tap water and the analyses of AA in fresh fruits with satisfactory results.

Since ribonuclease H (RNase H) exhibits its importance in a variety of cellular processes. It is necessary to establish strategy for RNase H detection. In this work, we are enlightened by mimosa, a natural plant which can fold in response to stimuli, to construct a DNA tetrahedron-based nanoprobe, termed DNA nanomimosa, to sensing RNase H activity based on fluorescent resonance energy transfer (FRET). The DNA nanomimosa was self-assembled from four DNA chains and one RNA chain. One of the four DNA chains contains a FRET-paired fluorophores-labeled hairpin DNA structures which is unfolded by the RNA chain through hybridization. Without RNase H, the RNA chain separate the two FRET-paired fluorophores in hairpin DNA structure, giving a feeble FRET signal. However, the presence of RNase H can selectively digest the RNA strand in RNA/unfolded-hairpin DNA section, resulting in the hairpin DNA configuration changed from "unfolded" state to "folded" state and further turn on the FRET signal. The DNA nanomimosa can be applied to achieve the determination of RNase H activity by recording the emission intensity of donor and acceptor fluorophores. This strategy shows a low detection limit by 0.017 U/mL, good specificity, and distinct advantages like the self-delivery ability, good biocompatibility, and the capacity to minimize the effects of fluctuations. This design provides a potential application in ribonuclease research and could be expanded for other biomedical research and clinical diagnostics.

Herein, we construct an ingenious spatially localized amplification reaction (SLAR) by colocalizing the entropy-driven reaction (EDR) in a nanometer space, which greatly accelerates target conversion and realizes the sensitive detection of microRNA-21 (miRNA-21). A large number of EDR complex are hybridized with the prefabricated DNA scaffold via a DNA self-assembly strategy to form the SLAR nanoprobe. Target miRNA-21 triggers interval EDR along the long DNA scaffold, resulting in fluorescence recovery with high signal gain because of the fast release of reporter. Compared with reactions with diffusible components, spatial arrangement of all components of EDR on a nanoscale scaffold can increase the local concentration of reactants, accelerating the interaction between adjacent components, and can also avoid the influence of stochastic diffusion to reduce the unintentional binding interaction between further separated components. Therefore, this SLAR assay displayed an excellent analytical performance for miRNA-21 detection with a detection limit of 6 pM and showed good specificity in distinguishing miRNA-21 from similar miRNAs. In addition, the proposed assay has been experimentally demonstrated for estimation of miRNA-21 in MCF-7 and HeLa cells lysates, which exhibited great promise in the sensitive detection of biomarkers in early diagnosis.

The level of carcinoembryonic antigen (CEA) in serum has the significant reference value for early diagnosis and treatment of various cancers. However, the CEA detection still suffers from the issue of limited sensitivity and reliability. Herein, a fluorescence (FL)-infrared absorption (IRA) dual-mode nanoprobe was fabricated based on carbon dots (CDs)@SiO2 nanorod for CEA detection. The FL and IRA signals display no mutual interference and can verify each other, ensuring the reliability of assay results. The highly sensitive FL signal originating from the CDs is enhanced by the surface passivation of SiO2 and improves the overall sensitivity of the detection. The detection range spans 9 orders of magnitude and the limit of detection reaches 794.6 ag mL−1, which are great superior to the commercial kits and most of the previous reports. Satisfactory recovery over the commercial kits was achieved in real serum samples. The ultrasensitive and reliable FL-IRA detection strategy sheds light on a new avenue toward promoting the practicability of the nanoprobes in clinical cancer diagnosis.

Peroxynitrite (ONOO−) is a series of basic biological oxidants involved in physiological and pathological processes. The detection of ONOO− in biological systems has been challenging due to its extremely short half-life and low steady-state concentration. In this work, a ratiometric fluorescent nanoprobe for ONOO− was constructed by coupling covalently of graphene quantum dots (GQDs) with cyanine 5.5 (Cy5.5). This nanoprobe (GQD-Cy5.5) could selectively accumulate in mitochondrial, appears two strong fluorescence emission peaks at 520 and 694 nm. In the presence of ONOO−, the intensity of fluorescence emission peak at 520 nm increased and the intensity of fluorescence emission peak at 694 nm decreased. The ratio (F520 nm/F694 nm) of fluorescence intensity at two emission peaks had a good linear relationship with the concentration of ONOO− in the range of 0–6.0 μM, and the detection limit was 0.03 μM. The excellent properties of the nanoprobe enable its applications in the ratiometric fluorescence imaging of endogenous ONOO− in cell mitochondria.

MicroRNAs (miRNAs) are regarded as important biomarkers for disease diagnostics and therapeutics due to their significant regulatory roles in physiologic and pathologic processes. Herein, a versatile nanoprobe based on reduced graphene oxide (rGO) and nucleic acid (DNA) probe was prepared for simultaneously visualize miR-451a and miR-214–3p in living cells. In vitro experiments demonstrated that the nanoprobe exhibits excellent selectivity and outstanding sensitivity as low as 1 nM towards miR-451a and miR-214–3p. Moreover, the detection signals of miRNAs have good linearity in their respective concentration ranges (miR-451a: 1–100 nM, Y1 = 9.3062X1+114.85 (R2 = 0.9965). miR-214–3p: 1–200 nM, Y2 = 1.4424X2+91.312 (R2 = 0.9961)). Finally, simultaneous dual-color imaging of miR-451a and miR-214–3p in human breast cancer cells (MDA-MB-231) was realized by exploiting the P1&P2@rGO nanoprobe. In summary, this simple and effective strategy provides a general sensing platform for highly sensitive detection and simultaneous imaging of dual miRNAs in living cells.

Accurate and selective in-field detection of metal ions in complex media has gained wide interests due to the complexed matrices and weak affinity towards sensing surface. Herein, we develop a first trimodal method for sensing of Zn2+ in complex matrices by stimuli-responsive N-[6-piperazinyl-2-pyridinyl]-N-(2-pyridinylmethyl)-2-Pyridinemethanamine dithiocarbamates (DPY) modified gold nanorods (GNRs-DPY). The presence of Zn2+ triggers the aggregation of GNRs-DPY, leading to increment of color and fluorescence intensity of the sensing system, which could be visually discerned with bare eye. Moreover, the intensive electromagnetic enhancement among “hot spots” of GNRs, generated during self-aggregation of the GNRs-DPY caused by Zn2+, lowers the detection limit of SERS assay to 6 × 10−3 pM. It is noteworthy that GNRs-DPY based sensing platform not only enables distinguishing Zn2+ from Cd2+, with simplicity and rapidity, but also demonstrates as trimodal nanoprobe for sensitive and selective quantitative determination of Zn2+ in different matrices. Therefore, the GNRs-DPY provides a new strategy for accurate and credible on-spot determination of Zn2+ in complicated specimens, as well as offering multiple applications in point-of-care monitoring.

Rare earth (RE) complexes have found a variety of applications in materials science and biomedicine because of their unique luminescence properties. However, the poor stability and solubility in water of multicomponent RE assemblies significantly limit their practical applications. We rationally designed and developed a novel Eu3+/Tb3+ supramolecular assembly hybrids (Eu/Tb-SAH) by supramolecular host-guest recognition and coordination recognition with the excellent characteristics of water dispersion stability, biocompatibility and luminous properties. As anthrax spore biomarker, 2,6-pyridinedicarboxylic acid (DPA) can coordinate with Tb3+ and sensitize Tb3+, resulting in a proportional change of fluorescence intensity and lifetime on the ms timescales, thereby realizing rapid and sensitive detection of DPA in water media or actual spores. To confirm our prediction, accurate and selective detection of DPA was achieved with Eu/Tb-SAH as a nanoprobe through steady-state ratiometric fluorescence and time-resolved technology, of which the limit of detection (LOD) are 27.3 nM and 1.06 nM, respectively. This was obviously lower than the amount of anthrax spores infecting the human body (60 μM). Besides, the filter paper was used to carry out visual detection of DPA and read the corresponding data through smart phones. This work paves a new way to fabricate luminescent RE nanomaterials and provides new ideas for the design of ratiometic lifetime imaging biosensors in the meantime.

Glutathione (GSH) serves several vital biological functions and its abnormal levels are associated with many diseases. Simple and sensitive methods capable of detecting GSH are desired for better understanding the mechanism of diseases. In this work, a label-free MnO2 nanosheets assisted aggregation-induced emission (AIE)-silica nanospheres (SiO2 NPs) nanoprobe for fluorescent "turn-on" detection of GSH with high sensitivity was reported for the first time. The anionic tetraphenylethylene derivative 3 (TPE3) was synthesized and employed as the AIE-active probe, which can be aggregated on the uncoated amino-functionalized SiO2 NPs to form AIE-SiO2 NPs and emitted strong fluorescence. Negatively charged MnO2 nanosheets were employed as both positive charge protectors for amino-functionalized SiO2 NPs and recognition units for GSH. The presence of GSH could selectively reduce MnO2 nanosheets to Mn2+, thus releasing the amino-functionalized SiO2 NPs and exposure its positive charges. Accordingly, the TPE3 could be aggregated on the exposured amino-functionalized SiO2 NPs to form AIE-SiO2 NPs and emitted strong fluorescence. The proposed assay is simple, fast, low cost, and highly sensitive with a detection limit of 200nM for GSH. The assay was further applied in human serum samples for the detection of GSH with satisfactory results, demonstrating its promising application in practical biological samples.

Sialic acid (SA) is a special monosaccharide widely distributed at the termini of sugar chains on the cell surface, and its expression level is closely connected with various biological and pathological processes. Therefore, accurate quantitative detection of SA on cancer cell surface is of great significance for clinical diagnosis and therapy. Here, we developed a whole-surface accessible method of accurate SERS quantification of SA level on a single cell, in which silver nanoparticles functionalized with 4-mercaptophenylboric acid and 4-mercaptobenzenitrile was used as the background-free SERS probe. The cyano group on the nanoprobe showed a unique Raman shift at 2232 cm−1, where most of the biological samples have no Raman response. Meanwhile, the boronic acid group had high specificity to SA molecules at physiological pH. The expression level of SA can be accurately quantitated on the basis of the C N Raman signal. The average number of expressed SA molecules on the surface of a single HeLa cell was 4.6 × 107. And SERS imaging of a single cell was achieved at 2232 cm−1 without biological interference. We evaluated SA expression level on the surface of different cancer cells and dynamically monitored SA expression under the influence of drugs. The proposed approach is accurate as well as sensitive for background-free quantification of SA on cell surface, which is promising for revealing the relationship between tumors and cell surface glycosylation.

Hemoglobin (Hb) plays an important role in oxygen carriage for mammals, which is also a typical biomarker for certain diseases. Although numerous methods had been developed for the detection of Hb in red blood cells, analytical technology for the monitoring of low-abundance Hb in serum or plasma is still a challenge. Herein, persistent luminescence nanoparticles (PLNPs) with strong near-infrared (NIR) emission character behaving as a label-free probe for the highly sensitive and selective detection of Hb were developed. Further studies revealed that the sensing mechanism should be attributed to the Hb-induced dynamic quenching process. Moreover, the nanoprobe showed high selectivity to Hb against the common existing substances in human serum and a linear response to Hb ranging from 1 to 50 nM with an extremely high limit of detection (LOD) of 0.13 nM. Finally, applicability of the proposed probe for the detection of Hb in human serum samples was validated.

In this work, we developed an effective voltammetric immunosensing platform for the sensitive detection of prostate specific antigen (PSA) utilizing a graphene oxide (GO) modified screen-printed carbon electrode (SPCE) hybridized with the ex-situ prepared silver nanoparticles (AgNPs) as a probe and signal transducer. The sensing platform comprises a direct-type immunoassay involving the selective interaction of PSA with anti-PSA. The surface morphology and analytical performance of the modified SPCE were characterized through relevant instrumentations. The changes in the voltammetric reduction current of AgNPs at 0.11 V in the sensor electrode was correlated to the PSA concentration. Under optimum conditions, the fabricated immunosensor exhibited a sensitive response to PSA with a limit of detection (LOD) of 0.27 ng mL−1 and a dynamic calibration range of 0.75–100.0 ng mL−1. We demonstrated that the participation of AgNPs along with GO modification contribute to the desired signal amplification and sensitive detection of PSA. It is anticipated that the proposed immunosensor can serve as a biomarker and potentially be utilized for the real sample quantification of PSA.

A facile and rapid synthesis of multifunctional carbon nanodots (CNDs) was developed by using the acid-base neutralization spontaneous heat with glucose as precursor, 1,2-ethylenediamine (EDA) and concentrated nitric acid as dual N-dopants. The CND has a tremendous antioxidant potency, which represents effective inhibitory concentrations of reactive oxygen species that are significantly lower than ascorbic acid. Furthermore, minimum inhibitory concentration (MIC) assay revealed CNDs possessed significant antimicrobial activity for Gram-positive S. aureus and Gram-negative E. coli. Moreover, the CNDs are endowed with favorable fluorescence (FL) behaviors including the quantum yield (QY) of 14.2% and stable FL within a wide range of pH and high tolerance to external ionic strength, rendering them applicable in quercetin (QCT) detection as a FL nanoprobe. The CNDs were effectively quenched by QCT due to static quenching which takes place by the electrostatic interaction between basic groups of CNDs and QCT of 3-hydroxyl. This nanoprobe had profitable selectivity and sensitivity towards QCT with a linearity ranging from 1 μM to 47 μM and a low detection limit of 172.4 nM and were successfully performed for QCT detection in human serum and urine samples.

Typically, sialic acids (SA) with a nine-carbon backbone are found at the glycan chain termini on the cell membranes, which play crucial roles in various physiological and pathological processes. The expression level of SA in the blood serum has been reported to correlate with various disease states among cancer. In this study, a novel approach for preparing fluorescent boronic-acid-modified carbon dots (C-dots) for the detection of SA was developed. The functionalized C-dots were synthesized by a facile, one-step hydrothermal method using 3-pyridineboronic acid as the sole carbon source. The added SA selectively recognized the C-dots, leading to the fluorescence quenching of the C-dots in a linear range of 80–4000 μM with a detection limit of 54 μM. The as-developed boronic-acid nanoprobe was successfully applied for the detection of SA in human serum samples with satisfactory results. In addition, this method afforded results within 4 min. Compared to other methods, this new proposed approach was simpler and exhibited excellent sensitivity and selectivity, demonstrating immense potential as an alternative for SA detection.

Herein, we have synthesized Gd2O3:Yb,Er@UiO-66-NH2 (UiO-66-NH2 represent a zirconium-based metal organic framework [Zr6O4(OH)4(ata)12], ata: 2‐aminoterephthalate) core-shell composites to develop an upconversion fluorescent nanoprobe for efficient detection of trace methylene blue (MB) and ferrous ions (Fe2+). Due to the fluorescence of the nanoprobe can be quenched by MB based on inner filter effect, but gradually recover when contact with ·OH, which is generated from the reaction between H2O2 and Fe2+, we have achieved the detection of Fe2+. The detection linear range is from 1.78 to 15.8 μM, and the limit of detection (LOD) is 0.071 μM. Besides, in this process, we also simultaneously realize the detection of MB. The linear range of MB turn-off detection is 0–42.6 μM, and the LOD is 0.41 μM. To our knowledge, no example of using upconversion fluorescence probe for continuous detection of trace MB and Fe2+ has been reported for now, and test results are superior compared with most reported Fe2+ probes. Moreover, the combinations of upconversion nanoparticles (UCNPs) and the metal-organic frameworks (MOFs) have enhanced the selectivity and sensitivity of the probe towards MB and Fe2+. Therefore, we believe the designed upconversion fluorescent nanoprobe is a promising efficient tool in detecting MB and diagnose Fe2+ related diseases in the future.

Exosomes carrying abundant information have aroused great interest as effective biomarkers in liquid biopsy and are therefore ideal candidates for the early diagnosis of cancer and treatment monitoring. Herein, we developed a sensitive electrochemical biosensor using in situ generation of Fe₄[Fe(CN)6]₃ (Prussian Blue) on the surface of Ti3C2 MXene (two-dimensional transition-metal carbides) as hybrid nanoprobes (PB-MXene) for the detection of exosomes and their surface protein. A CD63 aptamer-modified poly(amidoamine) (PAMAM)-Au NP electrode interface was fabricated that can specifically bind with CD63 protein on the exosomes derived from OVCAR cells. In addition, the CD63-modified Ti3C2 MXene was used as a nanocarrier to accommodate numerous aptamers and was adsorbed on the exosomes. The Ti3C2 MXene can realize the in situ generation and high-efficiency loading of PB and further amplify the electrochemical signal at a low potential, thus avoiding the interference of the electrochemical active species. The dual amplification effect enables highly selective and sensitive electrochemical detection of exosomes. The limit of detection (LOD) was 229 particles μL−1 with a linear range from 5 × 102 particles μL−1 to 5 × 105 particles μL−1. An electrochemical biosensor can detect exosomes secreted by various cancer cells such as HeLa, OVCAR and BT474, and shows a high specificity even in serum samples, thus demonstrating its great potential in the application of clinical diagnostics. This proposed electrochemical biosensor provides a facile and efficient tool for the early diagnosis of cancers.

The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au–Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au–Se bond. The nanoprobe can specifically respond to MMP-2/7/9, thereby triggering the fluorophores' fluorescence that quenched previously by fluorescence resonance energy transfer (FRET) to realize the MMP-2/7/9's visualization in biological systems. Moreover, as the inflammation stimulated by different concentrations lipopolysaccharide (LPS), the expression of MMP-2/7/9 in SMMC-7721 cells was observed to be significantly enhanced by confocal laser scanning microscope (CLSM) imaging, and inflammation was further proved to intensify SMMC-7721 cells' invasion and migration by transwell invasion and migration experiments. Therefore, the nanoprobe can be used to monitor biomarkers to provide a visual system for the degree of invasion and migration of tumor cells in an inflammatory environment, and also offer a new strategy for the study of the correlation between various active biomacromolecules and specific intracellular pathways in cells.

Near−infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent fluorescent nanoprobes for bioassays with low toxicity. A novel fluorescent sensing platform which employing NIR fluorescent Ag2S QDs and MnO2 2D nanosheets as NIR emitters and quenchers is designed for rapid and selective determination of glutathione (GSH). A facile and efficient approach was demonstrated for the synthesis of NIR fluorescent Ag2S QDs with the emission of 845 nm. Then the NIR fluorescent nanoprobe of Ag2S QDs−MnO2 nanosheets is obtained by adsorbing Ag2S QDs onto the surface of MnO2 nanosheets which have atomically thick two−dimensional structure and high specific surface area. And the NIR fluorescence of Ag2S QDs is quenched by the MnO2 nanosheets. The presence of GSH could reduce MnO2 to Mn2+ that results in the restoration of NIR fluorescence for Ag2S QDs. The NIR fluorescent nanoprobe could be used for highly selective detection of GSH. Also a low detection limit of 60 μmol/L was obtained. Because NIR fluorescence of the Ag2S QDs can efficiently reduce the interferences from background scattering and autofluorescence. The NIR fluorescent nanoprobe was directly applied to monitor the GSH level in human serum sample with high accuracy and precision.

A novel dual-emission nitrogen doped carbon dots/gold nanohybrid (NCDs-Au) was designed for specific and sensitive ratiometric detection of intracellular temperature and tyrosine. In this probe, a reductive NCDs was successfully prepared with the use of natural biomass Dendrobium officinale as precursor. The new prepared NCDs acted as both reducers and stabilizers to synthesize a novel NCDs-Au nanohybrid by a facile one-step procedure along with a quantum yield of 14.3%. The prepared nanoprobe showed characteristic fluorescence emissions of NCDs and Au NCs with single-wavelength excitation. Notably, the nanoprobe shows an interesting wavelength-dependent dual response to temperature (448 nm) and tyrosine (660 nm), enabling the two targets to be detected proportionally. As an effective temperature sensor, the nanoprobe exhibited good temperature-dependent fluorescence with a sensational linear response from 5 to 75 °C. In addition, the sensor has a linear response toward tyrosine in the range of 0.5–175 μM with a detection limit of 0.19 μM. Moreover, the fluorescent nanoprobe was successfully applied to ratiometricly monitor the variation of temperature or tyrosine level in cells because of the low cytotoxicity, chemical stability and excellent fluorescence properties. These results suggested that the nanoprobe here has provided the possibility for rapidly biosensing with the acceptable selectivity and sensitivity.

A bioorthogonal Raman reporter-embedded Au-core and polydopamine-shell nanoprobe was initially designed and synthesized for live cell surface-enhanced Raman scattering (SERS) imaging in Raman-silent region. The firstly synthetic bioorthogonal Raman reporter (E)-2- ((4-(phenylethynyl) benzylidene)amino)ethanethiol (PBAT) provided intense Raman signal at 2220 cm−1 in Raman-silent region. And its synthetic method was environmentally benign, high yield and easy in operation. In addition, the hydrophobicity of PBAT led to slightly aggregation of gold nanoparticles, which enhance the SERS intensity of the nanoprobe through hot spots. Furthermore, owing to the remarkable biocompatibility of polydopamine (PDA), the SERS nanoprobe can be smoothly internalized into cancer cells to realize SERS imaging in Raman-silent region. Finally, the SERS mapping results confirmed that nanoprobe exhibited strong SERS signal intensity, excellent stability in complex biological environment and low toxicity inside live cancer cells. Therefore, the reporter-embedded core-shell nanoprobe has enormous potential of applications in biomedical diagnostics in the near future.

An enzyme-based dual-labeled nanoprobe is designed to fabricate a sensitive enzyme-amplified lateral flow biosensor for visual detection of mircoRNA-224 (miRNA-224). The recognition DNA probe (detection probe) and signal amplification enzyme (Horseradish peroxidase, HRP) are immobilized on gold nanoparticle (GNPs) surface, simultaneously. The capture DNA probes are immobilized on the test zone of the lateral flow biosensor. When miRNA-224 is present, the enzyme-based dual-labeled nanoprobes will be captured by forming the "sandwich structure" on the test zone of the lateral flow biosensor, enabling the visual detection for miRNA-224. Sensitivity is amplified by applying the 3,3,5,5-tetramethylbenzidine enzymatic substrate (TMB/H2O2 enzymatic substrate) onto the test zone. The enzymatic reactions between the HRP and the TMB/H2O2 enzymatic substrate will produce blue products, which deposit on the nanoprobe surface to enhance the visual effect and the corresponding response intensities of the test zone. This enzyme-amplified lateral flow biosensor shows a low limit of detection (LOD) (7.5 pM) toward miRNA-224 in the buffer solution, which is improved by 10-fold than that of the single-labeled lateral flow biosensor. This biosensor has been successfully used for the detection of the target miRNA-224 detection in A549 cell lysate.

This study reports an Fe(3+)-functionalized carbon quantum dots (Fe(3+)-functionalized CQDs) for the highly sensitive and selective detection of ascorbic acid (AA) in rat brain microdialysates based on the specific redox reaction between iron(III) ions and AA. The carbon quantum dots (CQDs) were synthesized by one-step pyrolysis of a small organic molecules i.e. tris(hydroxymethyl)aminomethane (Tris). Fe(3+) can tightly chelate to the surface of CQDs by the hydroxyl group to form Fe(3+)-functionalized CQDs while the fluorescence of CQDs can be effectively quenched by Fe(3+) via Fluorescence resonance energy transfer (FRET). The fluorescence of the Fe(3+)-functionalized CQDs can be sensitively turned on by AA to give an "on-off-on" fluorescence response through the oxidation-reduction between Fe(3+) and AA since the produced Fe(2+) has much lower chelating ability to CQDs and the fluorescence of CQDs can be restored. This Fe(3+)-functionalized CQDs based nanoprobe shows high selective and sensitive response in the concentration of AA ranging from 0.1 μM to 50 μM with the detection limit as lower as 9.1 nM, which is lower than other assays. Finally, the proposed fluorescent probe was successfully applied to direct analysis of AA in biological fluids, i.e. rat brain microdialysates, and may pave a new route to the design of effective carbon quantum dots-based fluorescence probes for other bioassay.

Gold nanorods have been nominated as propitious candidates for nanobiodiagnostic applications. Herein, a technique has been introduced for rapid visual detection of lysozyme, as its high level of excretion in biological fluids is a characteristic sign of leukemia and kidney disorders. Gold nanorods were biofunctionalized with lysozyme aptamer and characterized with UV-Visible and FTIR spectroscopy, zeta potential analyzer and transmission electron microscopy. Exposure of the nanoprobe to nano molar levels of lysozyme (20 nmol l(-1)) lead to dictated aggregation of the nanostructures at ambient temperature; which was significantly improved by heat induced morphological perturbations and rapid detection by the naked eye (down to pico molar level). Qualitative analysis of Acute myeloid leukemia, Acute lymphocytic leukemia and Lymphoma blood serums showed sensitivity and specificity of the fabricated aptasensor under both temperature conditions. This report encourages utilization of heat-induced aggregation of gold nanorods as a promising nanodiagnostic technique for the emerging nanotechnologies.

Multidrug resistance (MDR) is the main cause of treatment failure in clinical cancer chemotherapy due to the presence of P-glycoproteins (P-gp), which widely exist in stubborn drug-resistant tumor membranes and actively pump drugs from inside the tumor cell to the outside. In this study, we report a novel telomerase-responsive nanoprobe with theranostic properties for inhibiting P-gp expression and reversing MDR by gene silencing. This nanoprobe is composed of an AuNP assembled with telomerase primer, antisense oligonucleotide (ASO), and doxorubicin (Dox). When the designed nanoprobe is uptaken by the MDR cancer cells, the Dox and ASO are specifically released due to the extension of telomerase primer triggered by telomerase. The released ASO specifically hybridizes with multidrug resistance 1 (MDR1) mRNA sequence, which encodes the P-gp. As a result, the expression of P-gp is inhibited and the efflux of Dox is prevented with reduced MDR in cancerous cells. The results demonstrate that the nanoprobe based on telomerase switching for drug release and gene silencing, can both target cancer cells for delivering drugs and overcome the effect of efflux pumps. This work presents a novel paradigm for theranostics of MDR cancer and enhances the efficacy of chemotherapeutics.

Quantitative characterization of intracellular H2O2 content, which is still difficult by the conventional biochemical methods due to the lack of real-time and non-invasive technique of single cell measurement, is a useful solution for cell state assessment. Based on the surface enhanced Raman scattering (SERS), we construct a novel boric acid (BA) nanoprobe to perform quantitative characterization of H2O2 content, in which the p-thiol benzene boric acid (4-MPBA) reporter molecule modified with gold nanorods (AuNRs) is employed for Raman signal enhancement. The achieved result demonstrates obvious advantages of the synthesized AuNRs/4-MPBA/BA nanoprobe in measurement sensitivity of H2O2 content. Importantly, this AuNRs/4-MPBA/BA nanoprobe will provide a powerful tool for dynamic monitoring and quantitative characterization of intracellular H2O2 content during cell apoptosis or other cell growth processes, and then achieve important reference data for studying the corresponding molecular mechanism.

The rapid and sensitive visualization of 2,6-dipicolinic acid (DPA, a unique anthrax biomarker) is essential to prevent anthrax disease or biological terrorist attack. In this study, a Eu3+-labeled ethylenediaminetetraacetic acid loaded hyperbranched polyethyleneimine carbon nanodot (hPEI-CD-EDTA-Eu3+) nanoprobe has been proposed for the ratiometric DPA detection. The sensing mechanism is based on the rapid DPA-Eu3+ chelation within 30 s and subsequent enhanced fluorescence emission through the antenna effect. With the introduction of EDTA chelating unit, the resulted fluorescence of Eu3+-complex is greatly enhanced, which endows sensitive DPA perception. By employing hPEI-CD as the internal reference, ratiometric DPA sensing is realized with a good linearity in the concentration range from 1.0 to 100 nM, with a limit of detection of 190 pM (S/N = 3). The specific chelation affinity between Eu3+ and DPA provides satisfying selectivity over other amino acids and ions. Using nanoprobe-loaded polyvinylidene fluoride paper as the analytical device, point-of-care DPA visualization is achieved. Furthermore, the practical application of designed paper device is validated by the visual detection of metabolic DPA-release from Bacillus subtilis spores.

We report an attomolar sensitive electrochemical genosensor for the detection of cauliflower mosaic virus 35S (CaMV35S) gene. The sandwich-type genosensor uses gold-silver core-shell (Au@Ag)-loaded iron oxide (Fe3O4) nanocomposite (Fe3O4-Au@Ag) as label of signal DNA probe (sDNA). Electrochemical sensing is accomplished at interface of electrodeposited AuNPs and carboxylated multiwalled carbon nanotubes-modified glassy carbon electrode through the specific interaction between the capture probe and target CaMV35S (tDNA), and tDNA and the labeled sDNA. The detection sensitivity was improved by the amplified reduction signal of hydrogen peroxide (H2O2), which takes advantage of the enhanced electrocatalytic activity of Fe3O4-Au@Ag. Under the optimal experimental conditions, an ultralow limit of detection was calculated to be 1.26 × 10−17 M (S/N = 3), and the blank value subtracted reduction signal of H2O2 of the sensor increased linearly with the logarithm of CaMV35S concentration over a wide range (1 × 10−16 M to 1 × 10−10 M). This genosensor displayed excellent stability, selectivity and reproducibility, and was successful in detecting the target CaMV35S in genetically modified tomato samples.