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Functional nanomaterials possess exceptional multi-physical (e.g., mechanical, electrical and optical) properties compared with their bulk counterparts. To facilitate both synthesis and device applications of these nanomaterials, it is highly desired to characterize their multi-physical properties with high accuracy and efficiency. The nanomanipulation techniques under scanning electron microscopy (SEM) has enabled the testing of mechanical and electrical properties of various nanomaterials. However, the seamless integration of mechanical, electrical, and optical testing techniques into an SEM for triple-field-coupled characterization of single nanostructures is still unexplored. In this work, we report the first SEM-based nanomanipulation system for high-resolution mechano-optoelectronic testing of single semiconductor InGaN/GaN nanowires (NWs). A custom-made optical measurement setup was integrated onto a four-probe nanomanipulator inside an SEM, with two optical microfibers actuated by the nanoma-nipulator for NW excitation and emission measurement. A conductive tungsten nanoprobe and a conductive atomic force microscopy (AFM) cantilever probe were integrated onto the nanomanipulator for electrical nanoprobing of single NWs for electroluminescence (EL) measurement. The AFM probe also served as a force sensor for quantifying the contact force applied to the NW during nanoprobing. Using this unique system, we examined, for the first time, the effect of mechanical compression applied to an InGaN/GaN NW on its optoelectronic properties.

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

Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.

Cerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it’s interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.

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

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

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

Sensitive detection of redox active analytes utilising its fluorescent nature requires a direct non-complicated approach to amplify its emission intensity. In this regard, we investigated nanoscale cerium oxide for its unique nanosized structure, surface reactivity and redox activity coupled with surface complexation. Variations in either oxidation state or the surface-terminated oxygen of the cerium oxide nanoparticales provide gaps for the adsorption of redox functionalities. It enables ceria particles to concentrate the analyte molecules on their surface promoting fluorescence signal amplification. As a proof of concept, we integrated surface complexation feature of nanoceria towards improved fluorescent response and successively implemented them for ultra-sensitive identification of a redox active Ochratoxin A (OTA) at specific wavelength range. Results obtained indicate that higher amplification efficacy of nanoparticles is due to its higher electron mobility along with good absorbability. Different identification techniques including XRD SEM, UV–Vis, EDX, FTIR, photoluminescence, RAMAN spectroscopy and finally fluorescence assays were performed to examine morphology and nano-surface chemistry along with signal amplified strategy of the developed nano-probe. Various experimental factors including incubation time, pH and concentrations of OTA and ceria particles were also optimised. Under optimised environment, the limit of detection was as smaller as 0.1 ng mL−1 with 0.5–100 ng mL−1of linear range. Thus, we proposed a highly sensitive and selective fluorescent nanoprobe for analytical applications based on surface complexation affinity and fluorescence signal amplification ability of nanoceria.

Stimulated-emission depletion (STED) microscopy has profoundly extended our horizons to the subcellular level1–3. However, it remains challenging to perform hours-long, autofluorescence-free super-resolution imaging in near-infrared (NIR) optical windows under facile continuous-wave laser depletion at low power4,5. Here we report downshifting lanthanide nanoparticles that enable background-suppressed STED imaging in all-NIR spectral bands (λexcitation = 808 nm, λdepletion = 1,064 nm and λemission = 850–900 nm), with a lateral resolution of below 20 nm and zero photobleaching. With a quasi-four-level configuration and long-lived (τ > 100 μs) metastable states, these nanoparticles support near-unity (98.8%) luminescence suppression under 19 kW cm−2 saturation intensity. The all-NIR regime enables high-contrast deep-tissue (~50 μm) imaging with approximately 70 nm spatial resolution. These lanthanide nanoprobes promise to expand the application realm of STED microscopy and pave the way towards high-resolution time-lapse investigations of cellular processes at superior spatial and temporal dimensions. The application of stimulated-emission depletion (STED) microscopy for deep-tissue imaging in the near-infrared optical window is challenged by high cellular autofluorescence. Here the authors present a lanthanide nanoprobe whose electronic configuration enables long-term STED imaging with reduced background noise.

The development of aggregation-induced emission enhancement (AIEE) active nanoprobes without any synthetic complication for solution-state and organic thin-film transistor (OTFT)-based sensory applications is still a challenging task. In this study, the novel pyrene-incorporated Schiff base (5-phenyl-4-((pyren-1-ylmethylene)amino)-4H-1,2,4-triazole-3-thiol; PT2) with an AIEE property was synthesized via a one-pot reaction and was reported for detecting Zn2+ and tyrosine in the solution state and OTFT. In the AIEE studies of PT2 (in CH3CN) at various water fractions (fw: 0-97.5%), the existence of J-aggregation, crystalline changes, and nanofibers formation was confirmed by ultraviolet absorption/photoluminescence (UV/PL) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic-light scattering (DLS) techniques. Similarly, PT2-based Zn2+ detection and sensory reversibility with tyrosine were demonstrated by UV/PL studies with evidence related to crystalline/nanolevel changes in PXRD, SEM, TEM, AFM, and DLS data. Distinct decay profiles associated with the AIEE and sensory responses of PT2 were observed in time-resolved photoluminescence spectra. From the standard deviation and linear fittings of PL titrations, detection limits (LODs) of the Zn2+ with PT2 and the tyrosine with PT2-Zn2+ were estimated as 0.79 and 45 nM, respectively. High-resolution mass and 1H NMR results confirmed 2:1 and 1:1 stoichiometry and binding sites of PT2-Zn2+-PT2* and tyrosine-Zn2+ complexes. Moreover, the values of association constants determined by linear fittings were 4.205 × 10-7 and 1.73 × 10-8 M-2, correspondingly. Optimization via the density functional theory disclosed the binding sites and suppression of twisted intramolecular charge transfer/photoinduced electron transfer (TICT/PET) as well as the involvement of restricted intramolecular rotation in the AIEE and PET "ON-OFF-ON" mechanisms in the Zn2+ and tyrosine sensors. Results from the B16-F10 cellular and zebrafish imaging of AIEE, Zn2+, and tyrosine sensors further attested the applicability of PT2 in biological samples. Finally, the PT2 and pentacene-incorporated OTFT devices were fabricated. The devices displayed more than 90% change in drain-source current when reacted with Zn2+ with an LOD of 5.46 μM but showed no response to tyrosine, thereby confirming the reversibility. Moreover, the OTFT devices also demonstrated Zn2+ ion detection in tap water and lake water samples.

Detection of uric acid (UA) is inevitable today, as very less amount of uric acid in human leads to Fanconi Syndrome, Wilson’s disease and cardiovascular disorders. Here, we report an eco-friendly synthesis of a nitrogen-doped carbon dot/Chromium (VI) [N–C dot/Cr (VI)] fluorescent nanoprobe for nanomolar detection of uric acid. N–C dot/Cr (VI) nanoprobe is synthesized using solvent free, fast, easy, green, pyrolysis method, which is characterized using UV–VIS, FTIR, XRD, SEM- EDX and PL technique. Addition of Cr (VI) to fluorescent N–C dot leads to immediate turn OFF in fluorescence with the formation of N–C dot/Cr (VI) nanocomposite. The lowest detection limit of Cr (VI) by N–C dot is 1.42 × 10–9 M. For the first time, we are reporting uric acid, a reducing agent to reduce Cr (VI) to lower valent Cr (III)/Cr (0). The addition of uric acid turns ON the fluorescence with the elimination of inner filter effect (IFE) thus N–C dot/Cr (VI) nanoprobe functioning as a Turn Off–On fluorescent nanosensor for the detection of UA. The efficiency of the sensor is based on fluorescence resonance energy transfer between N-Carbon dots and chromium (VI). A linear response was noted with every nanomolar addition of uric acid. The lowest detection limit toward sensing of UA is found to be 12.5 × 10–9 M. Thus, the novelty of this method is nanomolar amount of redox species is enough to form a stable nanocomposite and the N-CDs/Cr (VI) nanocomposite is able to sense nanomolar to millimolar concentration of uric acid within a few seconds. The nanoprobe is found to be stable, simple and cost effective which can be extended for detection of uric acid in vegetables, fruits and also in clinical studies.

The design and operational performance of beamline I14, the Hard X-ray Nanoprobe at Diamond Light Source, is presented., The Hard X-ray Nanoprobe beamline, I14, at Diamond Light Source is a new facility for nanoscale microscopy. The beamline was designed with an emphasis on multi-modal analysis, providing elemental mapping, speciation mapping by XANES, structural phase mapping using nano-XRD and imaging through differential phase contrast and ptychography. The 185 m-long beamline operates over a 5 keV to 23 keV energy range providing a ≤50 nm beam size for routine user experiments and a flexible scanning system allowing fast acquisition. The beamline achieves robust and stable operation by imaging the source in the vertical direction and implementing horizontally deflecting primary optics and an overfilled secondary source in the horizontal direction. This paper describes the design considerations, optical layout, aspects of the hardware engineering and scanning system in operation as well as some examples illustrating the beamline performance.

Quantitative characterization of Cr3+, an important element revealing human metabolism and biological environmental variation, is still difficult to achieve by conventional biochemical methods due to the lack of high-sensitivity, real-time techniques with rapid response detection. Using surface-enhanced Raman scattering (SERS), we construct an Au/Ag composite-based SERS nanoprobe for the quantitative characterization of Cr3+ content in solution, in which DL-mercaptosuccinic acid (DL-MSA) is employed for Raman signal enhancement, and 4-mercaptobenzoic acid (4-MBA) is chosen as the Raman reporter. The achieved result demonstrates obvious advantages of the synthesized Au/Ag composite-based SERS nanoprobe in sensitivity and response speed. Importantly, this Au/Ag composite-based SERS nanoprobe might provide a new strategy for dynamic monitoring of Cr3+ content in human metabolism.

In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O2-generated nanozyme with intelligent "off/on" modulation and enhancement. Herein, a kind of H2O2-responsive nanozyme was developed for off/on modulation and enhancement of magnetic resonance (MR) imaging and PDT, in which great amounts of gold nanoclusters (AuNCs) were loaded into mesoporous silica to form nanoassembly, and manganese dioxide (MnO2) nanosheets were wrapped as switching shield shell (AuNCs@mSiO2@MnO2). In a neutral physiological environment, stable MnO2 shells eliminated singlet oxygen (1O2) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO2 shell reacted with H2O2, in which MnO2 degradation switched on MR imaging and PDT, and the generated O2 further enhanced PDT. H2O2-responsive MnO2 degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM-1 s-1, and simultaneously sufficient O2 generation guaranteed a 74% high 1O2 yield. Under the irradiation of a 635 nm laser, the viability of MDA-MB-435 cells was reduced to 4%, and the tumors completely disappeared, demonstrating strong PDT performance. Therefore, H2O2-responsive AuNCs@mSiO2@MnO2 nanozyme showed excellent off/on modulation and enhancement of MR imaging and PDT and was a promising intelligent nanoprobe for safe and high-efficiency theranostics.

Intelligent systems that offer traceable cancer therapy are highly desirable for precision medicine. Although photodynamic therapy (PDT) has been approved in the clinic for decades, determining where the tumor is, when to irradiate, and how long to expose to light still confuse the clinicians. Patients are always suffering from the phototoxicity of the photosensitizer in nonmalignant tissues. Herein, an activatable theranostic agent, ZnPc@TPCB nanoparticles (NPs), is prepared by doping a photosensitizer, ZnPc, with an aggregation-induced emission probe, TPCB. The assembled or disassembled ZnPc@TPCB NPs in various phases have behaved differently in fluorescence intensity, photoacoustic (PA) signals, and PDT efficiency. The intact nanoparticles are non-emissive in aqueous media while showing strong PA signals and low PDT efficiency, which can eliminate the phototoxicity and self-monitor their distribution and image the tumors' location. Disassembling of the NPs leads to the release of ZnPc and its red fluorescence turn-on to self-report the photosensitizer's activation. Upon light irradiation, the reactive oxygen species (ROS) generated by ZnPc can induce cell apoptosis and activate the ROS sensor, TPCB, which will yield intense orange-red fluorescence and instantly predict the therapeutic effect. Moreover, enhanced PDT efficacy is achieved via the GSH-depleting adjuvant quinone methide produced by the activated TPCB. The well-designed ZnPc@TPCB NPs have shown promising potential for finely controlled PDT with good biosafety and broad application prospects in individual therapy, which may inspire the development of precision medicine.

Accurate diagnosis and efficient treatment of tumors are highly significant in battling cancer. Near-infrared II (NIR-II) fluorescence imaging shows big promise for deep tumor visualization in living systems due to high temporal and spatial resolution and deep tissue penetration capability, whereas the development of efficient NIR-II probes for tumor theranostics still faces a huge challenge. Herein, we have designed and constructed intelligent mPEG5000-PCL3000-encapsulated NIR-II nanoprobe ZM1068-NPs that showed great chemical stability and excellent biocompatibility. With the merits of the strong fluorescence in the NIR-II region and prominent optical-thermal conversion efficiency, this probe was successfully used for NIR-II imaging-guided surgery and photothermal therapy of breast carcinoma in living mice. More notably, it was for the first time found that ZM1068 dyes could be covalently on-site-immobilized within tumors through the thiol-chlor nucleophilic substitution reaction, resulting in improved tumor accumulation and retention time. We thus envision that this probe may provide an attractive means for precise cancer diagnosis and treatment.

The establishment of sensing platform for trace analysis of Fe3+ in biological systems is meaningful for health monitoring. Herein, a Fe3+ sensitive fluorescent nanoprobe was constructed based on highly fluorescent N-doped carbon quantum dots (NCQDs) derived from bamboo stems through a hydrothermal method employing ethylenediamine as the nitrogen dopant. The prepared NCQDs had a uniformly distributed size and their mean size was around 2.43 nm. Abundant functional groups (C=N, N-H, C=O, and carboxyl) anchored on NCQDs demonstrated successful doping of N in CQDs. The obtained NCQDs possessed a high fluorescence quantum yield of 20.02% and outstanding fluorescence stability over a wide pH range and at high ionic strengths. Moreover, Fe3+ ions presented a specific fluorescent quenching effect to the as-prepared NCQDs. The calibration curve for fluorescence quenching degree corresponding to Fe3+ concentration showed a linear response in a range of 0.01–10 µM, and detection limit was 0.486 µM, which indicated that the NCQDs had high sensitivity to Fe3+ ions. Ascribed to these unique properties, the NCQDs were selected as luminescent probes for trace amount of Fe3+ ions in human serum. These results demonstrated their promising use in clinical diagnostics and other biologically relevant studies.

A novel copper ion sensing periodic mesoporous organosilica (SCN-PMO) was obtained by incorporating a Schiff base-based fluorescent receptor into the pore walls of mesoporous silica, which exhibited a well ordered mesoporous structure and excellent optical properties demonstrated by various characterization results. SCN-PMO possessed high selectivity and sensitivity towards Cu2+ based on its specific fluorescence response. The detection limit of SCN-PMO could be as low as 6.7 × 10-7 M. Due to protection of the silica network, SCN chromophores in PMOs exhibited higher photostability and the resulting material possessed great repeatability. Additionally, the fluorescence changes of SCN-PMO towards copper ions in vivo (zebrafish) showed that SCN-PMO has potential application as a nanoprobe in biological fields.

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.

Cu2+ is closely related to the occurrence and development of Wilson's disease (WD), and quantitative detection of various copper indicators (especially liver Cu2 and urinary Cu2+) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu2+ detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in determining WD status in real-time. Herein, we rationally designed a type of Cu2+-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(N-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu2+ content and urinary Cu2+ in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), respectively. In the nanoprobe, one Raman molecule of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman molecule mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu2+ can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm-1 of MBN is amplified, while the SERS signal at 1378 cm-1 of NAT remains stable, generating a ratiometric SERS I2223/I1378 signal. Both NIR-II PA1250 nm and SERS I2223/I1378 signals of the nanoprobe show a linear relationship with the concentration of Cu2+. The nanoprobe was successfully applied for in vivo quantitative detection of liver Cu2+ of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu2+ of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.

Metformin as a hypoglycemic drug for antidiabetic treatment has emerged as a multipotential drug for many disease treatments such as cognitive disorders, cancers, promoting weight loss. However, overdose uptake may upregulate the hepatic H2S level, subsequently leading to serious liver injury and toxicity. Therefore, developing intelligent second near-infrared (NIR-II) emitting nanoprobes by using endogenous H2S as a smart trigger for noninvasive highly specific in situ monitoring of the metformin-induced hepatotoxicity is highly desirable, which is rarely explored. Herein, an endogenous H2S activated orthogonal NIR-II emitting myrica rubra-like nanoprobe based on NaYF4:Gd/Yb/Er@NaYF4:Yb@SiO2 coated with Ag nanodots was explored for highly specific in vivo ratiometrically monitoring of hepatotoxicity. The designed nanoprobes were mainly uptaken by the liver and subsequently converted to NaYF4:Gd/Yb/Er@NaYF4:Yb@SiO2@Ag2S via in situ sulfuration reaction triggered by the overexpressed endogenous H2S in the injured liver tissues, finally leading to a turn-on orthogonal emission centered at 1053 nm (irradiation by 808 nm laser) and 1525 nm (irradiation by 980 nm laser). The designed nanoprobe presents a high detection limit down to 0.7 nM of H2S. More importantly, the in situ highly specific ratiometric imaging of the metformin-induced hepatotoxicity was successfully achieved by using the activatable orthogonal NIR-II emitting probe. Our results provide an NIR-II ratiometric fluorescence imaging strategy for highly sensitive/specific diagnosis of hepatotoxicity levels induced by metformin.

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r1 = 1.58 mM-1 s-1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.

Ultrasmall ferrite nanoparticles (UFNPs) have emerged as powerful magnetic resonance imaging (MRI) T1 nanoprobe for noninvasive visualization of biological events. However, the structure-relaxivity relationship and regulatory mechanism of UFNPs remain elusive. Herein, we developed chemically engineered 3.8 nm ZnxFe3-xO4@ZnxMnyFe3-x-yO4 (denoted as ZnxF@ZnxMnyF) nanoparticles with precise dopants control in both crystalline core and disordered shell as a model system to assess the impact of dopants on the relaxometric properties of UFNPs. It is determined that the core-shell dopant architecture allows the optimal tuning of r1 relaxivity for Zn0.4F@Zn0.4Mn0.2F up to 20.22 mM-1 s-1, which is 5.2-fold and 6.5-fold larger than that of the original UFNPs and the clinically used Gd-DTPA. Moreover, the high-performing UFNPs nanoprobe, when conjugated with a targeting moiety AMD3100, enables the in vivo MRI detection of small lung metastasis with greatly enhanced sensitivity. Our results pave the way toward the chemical design of ultrasensitive T1 nanoprobe for advanced molecular imaging.

We describe a label-free electrochemical aptasensor for adenosine triphosphate (ATP) assay based on bifunctional Fe3O4@Au nanocomposites. Due to the introduction of Au nanoparticles, the resulting bifunctional Fe3O4@Au nanocomposites can be easily modified with ATP-specific aptamer molecules through Au–S interaction to build the nanoprobe and used to immobilize on a glassy carbon electrode simply with the assistance of a magnet. Once exposed to the target ATP, the current signal obtained at nanoprobe-containing magnetic glassy carbon electrode decreases immediately. The decrease in sensor current is a result of the less methylene blue adsorbed on the aptamer caused by the fact that the ATP-specific aptamer prefers to bind with ATP rather than with methylene blue. The decrease in sensor current can be used for electrochemical determination of ATP, for example, to determine ATP in human serum samples.

The dual-mode bio-imaging nanoprobe TP-CQDs@MnO2, based on two-photon carbon quantum dots and MnO2, has been developed for the two-photon fluorescence and MR imaging of endogenous H2O2 in the tumor microenvironment, and it achieved high selectivity, a great signal-to-noise ratio, a limit of detection (LOD) of 1.425 pM for H2O2, and a two-photon tissue penetration depth of 280 μm.

This work reports donor–acceptor type sea urchin-like carbon nanobranched polymers (SUCNPs). As a novel carbon-based nanomaterial, SUCNPs were effectively synthesized for the first time through a facile and economical solvothermal approach employing uric acid and L-cysteine as nitrogen/sulfur sources. The nitrogen-rich structure of the heterocylic aromatic polymer led to a blue fluorescence at the excitation/emission maxima of 350/436 nm with robust photostability. SUNCPs showed highly selective ability towards hypochlorite (ClO−) against other relevant interfering substances. Upon exposure to a growing concentration of ClO−, SUCNPs fluorescence presented a gradual rise with a remarkable blue shift by virtue of the inhibition of photoinduced charge transfer (PCT) process. A linear relationship was established between the fluorescence intensity ratio (I401 nm/I436 nm) and the ClO− concentration in the range of 0.1–200 μM. The detection limit was as low as 30 nM (3σ/k). The “turn-on” type nanoprobe was further used in real samples and paper-based analytical chips efficiently, implying its application in a sophisticated and convenient platform.

Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T1–T2 switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T1 MRI enhancement (r2/r1 = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T2 MRI enhancement (r2/r1 = 13.326). Furthermore, an in vivo switch of T1–T2 enhancement modes shows that the vulnerable plaques exhibit strong T1 enhancement after intravenous administration of the nanoprobe, followed by a switch to T2 enhancement after 9 h. In contrast, stable plaques show only slight T1 enhancement but without T2 enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T1–T2 switchable process, which will significantly contribute to the application of materials science in solving clinical problems.

A nanoprobe based on polydopamine-coated gold nanobipyramids surface modified with molecules of a phenylboronic acid-substituted distyryl boron dipyrromethene has been fabricated and characterised using various physical and spectroscopic methods. It serves as an ultrasensitive sensor for sialic acids on the surface of cancer cells based on its dual surface-enhanced Raman scattering and fluorescence response. This biomarker can also trigger the photodynamic activity of these nanobipyramids, effectively eradicating the cancer cells mainly through apoptosis as shown by various bioassays.

Aggregation induced emission (AIE)-active bright two-photon fluorescent probes with second near-infrared (NIR-II) light excitability can be used for efficient brain bioimaging studies, wherein the fabrication of water-dispersible nanoparticles by encapsulating the hydrophobic probes with amphiphilic polymer holds the key to ensuring biocompatibility and in vivo adaptability. However, barely any study has evaluated the structural requirements that can substantially affect the water-dispersible nanoparticle formation ability of an organic AIE-active dye with amphiphilic polymers. The present study systematically assessed the structural dependency of a well-known acrylonitrile based AIE system/fluorogenic core upon the formation of water-dispersible nanoparticles and elucidated how the structural modifications can impact the in vivo two-photon imaging. Methods: A total of four acrylonitrile-based aggregation induced emission (AIE)-active two-photon (TP) fluorescent probes (AIETP, AIETP C1, AIETP C2 and AIETP C3) have been judiciously designed and synthesized with structural variations to realize how the structural alterations could substantially influence the water-dispersible nanoparticle formation ability (with amphiphilic polymers) and photo-stability to impact the in vivo imaging. Results: It has been found that the incorporation of the phenyl-thiazole unit in AIETP, AIETP C2 and AIETP C3 facilitated the formation of water-dispersible nanoparticles (NPs) with amphiphilic polymers (Pluronic F127) whereas the presence of only phenyl moiety instead in AIETP C1 could not meet the suitable condition to form the NPs with good aqueous dispersibility. Rationally designed AIETP NPs that exhibited higher brightness, improved photostability and good two-photon absorption cross section was successfully employed for in vivo brain vasculature imaging. Conclusions: Robust noninvasive 2D and 3D two-photon (NIR-II light, 1040 nm) brain vasculature imaging with beneficial attributes such as outstanding penetration depth (800 µm) and exceptional spatial resolution (1.92 µm), were achieved by utilizing AIETP NPs in this study.

Two-dimensional (2D) hexagonal boron nitride nanosheet (h-BNNS) is proposed as an effective nanoquencher for fluorescence detection of biocompatible microRNA. Compared with bulk hexagonal boron nitride (h-BN), the exfoliated ultrathin nanosheet has a narrow band gap and increased conductivity, thus enabling fast electron transfer with this electron acceptor for more effective fluorescence detection of microRNA. Remarkably, using the nanoprobe consisting of h-BNNS and FAM dye-labeled ssDNA, a low detection limit of 2.39 nM is achieved and a rapid fluorescence response is observed compared with previously reported fluorescence sensing materials. More importantly, this sensing system could also distinguish base-mismatched microRNA, suggesting that the proposed sensing platform held excellent selectivity and great promise for application in the detection of nucleotide polymorphism. This work will benefit microRNA-related fundamental research and disease diagnosis.

Successful and effective treatment of different types of infections depends upon fast and selective identification of the microorganisms. Pseudomonas aeruginosa is a Gram-negative bacterium which is involved in a number of human infections and may become life-threatening for immunocompromised persons. Pyocyanin is a unique exotoxin which is exclusively secreted as a virulence factor by P. aeruginosa. In this respect, a nano-assembly, composed of a carbon dot conjugated gold nanocomposite (Au@OPCDPEG) having a size of ∼11.5 ± 1.6 nm, was synthesized and used as both a fluorescence resonance energy transfer (FRET) and a colorimetric sensor for pyocyanin detection. When titrated with increasing concentrations of pyocyanin, Au@OPCDPEG NPs showed ∼1.76 ± 0.12 times increase in fluorescence intensity (at ∼505 nm), whereas three distinct isosbestic points were observed in absorption studies. The limit of detection for pyocyanin was found to be ∼3.04 ± 0.27 μM. It was found that Au@OPCDPEG NPs can selectively recognize pyocyanin even in the presence of other toxins under different biological interference. Real-time P. aeruginosa detection studies suggested the minimum detection limit to be ∼1.5 × 106 cfu ml−1 even in the presence of Staphylococcus aureus contamination in the sample. Confocal studies suggested that Au@OPCDPEG NPs can effectively penetrate P. aeruginosa biofilm under laser irradiation. Overall, the present engineered nanoprobe provides an easy, fast and selective method for the detection of P. aeruginosa in biological samples.

Colorectal cancer is one of the malignant tumors with high morbidity and lethality. Its efficient diagnosis and treatment has important significance. In this study, the orthotopic cancer model mouse, which could perfectly simulate clinical inflammatory colorectal cancer, was constructed by chemical induction. Based on this model, a new pH/ultrasonic dual-response, step-targeting and precisely controlled-release enteric-coated granule was designed for the combined sonodynamic (SDT)-chemotherapy. The enteric-coated granule was fabricated by enwrapping carboxymethyl chitosan (CMC) on folic acid-modified phospholipid (SLB-FA) encapsulating mesoporous silicon-coated gold nanoparticles loaded with chlorin (Ce6) and doxorubicin hydrochloride (DOX), titled as Au@mSiO2/Ce6/DOX/SLB-FA@CMC (GMCDS-FA@CMC). The diameter of the Au@mSiO2/Ce6/DOX/SLB-FA (GMCDS-FA) nanoprobe was 61.21 nm and that of the GMCDS-FA@CMC enteric-coated granule was 1.1 μm. MTT results showed that the cell survival rate was still as high as 76.55 ± 1.27% when the concentration of GMCDS-FA was up to 200 μg mL-1, which can indicate the low cytotoxicity of the nanoprobe. According to CT imaging, the enteric-coated granule had the highest concentration in the colorectum of the orthotopic cancer mouse after 7-9 h with oral administration, and was nearly metabolized out of the body after 24 h. The in vitro and in vivo experiments showed that the targeting enteric-coated granule had the best effect of treatment and desired prognosis after combined SDT-chemotherapy.

Gliomas are the most common primary brain tumors in adults, accounting for 80% of primary intracranial tumors. Due to the heterogeneous and infiltrating nature of malignant gliomas and the hindrance of the blood-brain barrier (BBB), it is very difficult to accurately image and differentiate the malignancy grade of gliomas, thus significantly influencing the diagnostic accuracy and subsequent surgery or therapy. In recent years, the rapid development of emerging nanoprobes has provided a promising opportunity for the diagnosis and treatment of gliomas. After rational component regulation and surface modification, functional nanoprobes could efficiently cross the BBB, target gliomas, and realize single-modal or multimodal imaging of gliomas with high clarity. Moreover, these contrast nanoagents could also be conjugated with therapeutic drugs and cure cancerous tissues at the same time. Herein, we focus on the design strategies of nanoprobes for effective crossing of the BBB, and introduce the recent advances in the precise imaging and therapy of gliomas using functional nanoprobes. Finally, we also discuss the challenges and future directions of nanoprobe-based diagnosis and treatment of gliomas.

Recently, multimodal imaging nanoprobes based on the complementary advantages of various imaging methods have attracted considerable attention due to their potential application in the biomedical field. As important bioimaging nanoprobes, lanthanide-doped nanocrystals (NCs) would be expected to improve the related biophotonic technology through integrated multimodal bioimaging. Herein, water-soluble and biocompatible NaYF4:Nd/NaDyF4 NCs were prepared by a solvothermal method combined with hydrophobic interaction with phospholipids as a capping agent. The NaYF4:Nd/NaDyF4 NCs exhibit excellent colloidal stability under physiological conditions. Compared with the bare NaYF4:Nd3+ NCs, the second near-infrared (NIR-II, 1000–1700 nm) fluorescence intensities of Nd3+ ions in the NaYF4:Nd/NaDyF4 core–shell NCs at the emissions of 1058 nm and 1332 nm are enhanced by 3.46- and 1.75-fold, respectively. Moreover, the r2 value of NaYF4:Nd/NaDyF4 NCs as T2-weighted contrast agents is calculated to be 44.0 mM−1 s−1. As a novel multimodal imaging nanoprobe, the NaYF4:Nd/NaDyF4 NCs can be employed for both NIR-II fluorescence and magnetic resonance imaging (MRI). The phospholipid-modified NaYF4:Nd/NaDyF4 NCs demonstrate in vitro and in vivo multimodal NIR-II fluorescence imaging and MRI of HeLa cells and tumors, respectively. This study provides an effective strategy for the development of novel multimodal probes for the medical application of nanomaterials.

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.

Herein, we report the in situ analysis of human telomerase by a multicolor DNA tetrahedron nanoprobe. The elongated telomeric repeats can hybridize with settled molecular beacons in order, accompanied by sequentially lighted up fluorescence. Imaging telomerase activity, real-time monitoring telomerase action and determining product length distribution in living cells are realized. It detects multiple information of intracellular telomerase and provides deeper insights into the function of telomerase.

Herein, we propose a dual-responsive fluorescent nanoprobe to visualize the cross-talk between O2 and adenosine triphosphate (ATP) in living cells. We hope it will be a helpful tool for the further understanding of cellular metabolism and further facilitating risk warning in the process of adaptation to consistent environmental pressures in premalignant lesions.

Aggregation induced emission (AIE) dots have gained broad attention in fluorescence bioimaging and biosensors in virtue of their distinctive optical properties of splendid biocompatibility, high brightness and good photostability. However, the application of AIE dots in sensing and imaging of enzymes in cells remains at an early stage and needs to be further explored. In this report, we proposed a novel AIE-dot-based nanoprobe for hyaluronidase (HAase) detection using a simple electrostatic self-assembly of AIE dots with gold nanoparticles functionalized using hyaluronic acid (HA-AuNPs), named HA-AuNPs@AIEDs. The fluorescence of AIE dots can be obviously quenched by HA-AuNPs via fluorescence resonance energy transfer (FRET). HAase could degrade HA into small pieces and thus induce disassembly of AuNPs and AIEDs, accompanied by fluorescence recovery of AIEDs. The as-prepared nanoprobe exhibited high sensitivity, excellent selectivity, wide response range and desirable anti-interference for quantitative sensing of HAase in vitro. The detection limit was down to 0.0072 U mL−1. Moreover, the nanoprobe displayed good biocompatibility and excellent photostability, and thus offered a practicable “turn-on” strategy for specific, high-contrast fluorescence imaging of HAase in live tumor cells. The AIE-based nanoprobe may provide a novel universal platform for recognition and imaging of HAase in tumors, and may be beneficial for related biological research.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 μM with a detection limit of 0.67 μM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

Tripeptide glutathione (GSH) is an abundant and ubiquitous metabolite in living organisms and plays critical roles in various cellular processes. In this work, we report the development of a new nanoprobe (MnO2–PEI–FITC) for GSH detection and imaging by exploiting the response mechanism of specific GSH-triggered reduction of manganese dioxide (MnO2) nanosheets. The MnO2–PEI–FITC nanoprobe was developed by coating negatively charged MnO2 nanosheets with a positively charged polyethylenimine (PEI) polymer, followed by coupling with fluorescein isothiocyanate (FITC) through a thiourea linkage. The MnO2–PEI–FITC nanoprobe showed weak fluorescence due to the quenching of FITC emission absorption by MnO2, while the emission of FITC at 518 nm was observed in the presence of GSH. The MnO2–PEI–FITC nanoprobe is featured with a rapid response to GSH (

A novel surface-enhanced Raman scattering (SERS) nanoprobe based on a reactive strategy was designed for the first time to determine the concentration of superoxide anion radical (O2˙−) produced from titanium dioxide by a UV radiation process. A limit of detection (LOD) for O2˙− of 9.0 nmol L−1 could be attained.

A novel chemiluminescence (CL) immunosensor using functionalized tungsten disulfide nanosheets (WS2 NSs)–gold nanoparticles (Au NPs)–horseradish peroxidase (WS2–Au–HRP) as multiple signal amplification probe was developed for prostate specific antigen (PSA) analysis. The WS2–Au nanocomposites were synthesized by in situ growth of Au NPs on the surface of WS2 NSs. HRP and antibody for recognizing the target were subsequently functionalized on WS2–Au. Owing to the large loading capacity of the WS2 NSs, the WS2–Au–HRP nanoprobe exhibits synergistic enhancement to the luminol–H2O2 CL system. The kinetics and spectra of CL from the luminol–H2O2–WS2–Au–HRP system were studied and the CL mechanism is discussed. Exemplified by PSA as target, the ultrasensitive CL immunoassay of PSA was achieved owing to the multiple signal amplification of the WS2–Au–HRP nanoprobe. The detection limit is 3.0 × 10−14 g mL−1 with a linear range of 1.0 × 10−13 to 1.0 × 10−8 g mL−1. Furthermore, the method was applied to human serum sample analysis with high selectivity and reproducibility. The method provides a novel ultrasensitive CL detection tool for biomarkers in real samples.

A method for detection and tracking of a multiprotein chip with a nanoprobe based on information communication is designed to detect the early markers of acute myocardial infarction, to solve the problem of long detection time of traditional detection and tracking methods. The sera of 42 patients with acute myocardial infarction were collected as the experimental objects. The experimental results show that the designed method for detection and tracking of a multiprotocol chip with a nanoprobe based on information communication has a shorter detection time for the early markers of acute myocardial infarction than the traditional method. This proves the validity of this study. When using this method to detect the sera of patients with acute myocardial infarction and normal people, the results are consistent with those of the electrochemical analysis method used in clinical studies. Therefore, it is proved that this method is simple, convenient and fast and has the advantages of high-sensitivity and multi-index detection. It has important value and application prospects in clinical protein detection.

Background Laryngeal cancer is the second most common type of primary epithelial malignant tumor in the head and neck region, and the development of therapies that are more precise, efficient, and safe is necessary to preserve patient speech and swallowing functions as much as possible. Multi-modal imaging-guided photothermal therapy (PTT) can precisely delineate tumors, monitor the real-time accumulation of photothermal agents at the tumor site, accurately select the optimal region for irradiation, and predict the best time for laser treatment. Compared with exogeneous photothermal agents, endogenous melanin materials have better biosafety in vivo, in terms of native biocompatibility and biodegradability, as well as good near-infrared (NIR) absorbance. An NIR-II dye can be attached to melanin via a facile method, and applying a melanin-dye-based nanoprobe could be an excellent choice for the elimination of superficial laryngeal cancer while avoiding total laryngectomy. Methods In this work, a promising nanoprobe was constructed using a facile EDC/NHS strategy involving an NIR-II dye and melanin nanoparticles. Results The nanoprobe exhibited good water solubility, dispersibility, strong NIR-II fluorescence and photoacoustic (PA) signals, and higher photothermal performance. Cellular studies showed that the nanoprobe had low toxicity, excellent biocompatibility, and significantly enhanced imaging properties. After the nanoprobe was intravenously injected into Hep-2 laryngeal xenografts, superior dual-modal images were obtained at various time points, which revealed that the optimal photothermal treatment time was 8 h. Subsequently, PTT was carried out in vivo, and laryngeal tumors were completely eliminated after laser irradiation without any obvious side effects. Conclusion These results indicate the immense potential of nanoprobes for the NIR-II fluorescence/PA imaging-guided photothermal therapy of laryngeal cancer.

Human telomerase has been identified as a potential tumor biomarker for early cancer diagnosis and cancer progression monitoring. We construct a novel magnetic targeting carbon nanocage/Fe3O4/DNA (CNC/Fe3O4/DNA) nanoprobe for intracellular imaging of telomerase via the signal amplification strategy catalyzed hairpin assembly (CHA) and for photodynamic-photothermal therapy of tumor cells. Telomerase primer DNA, trigger DNA, hairpin DNA1 (H1), and hairpin DNA2 (H2) were adsorbed to the surface of CNC/Fe3O4 nanoparticles (CNC/Fe3O4 NPs), and the fluorescence of (chlorin e6) Ce6 was quenched by CNC/Fe3O4 NPs. After entering the living cell through magnetic targeting, the telomerase primer DNA can be extended in the presence of highly activated telomerase, leading to the issue of trigger DNA, which can initiate the CHA cycling process followed by the amplification of the fluorescence intensity. The in vitro detection results justified that the proposed nanoprobe showed good sensitivity and selectivity for telomerase. Confocal microscopy studies indicated that such a nanoprobe can be used to detect the activity of telomerase in living cells and the fluorescence signal was stronger under the guidance of a magnetic field. We successfully employed this nanoprobe to monitor the dynamic activity of telomerase in various types of tumor cells and normal cells and to damage tumor cells by photodynamic-photothermal combination therapy, which evidenced that this is a promising biological method for early cancer diagnosis and tumor cell therapy.

Inorganic ion metabolism plays significant roles in various life processes including signal transduction, substance exchange, and cellular constructions. Regulation and monitoring of ion metabolism offer great promise to modulate biological activities and provide insights into related mechanisms. Here, a synergistic nanodepot based on a bioactive core-shell CaF2 upconversion nanostructure that integrates multiple mineral ions for metabolic regulation was built for the acceleration and monitoring of the biomineralization process. Multiple mineral ions released from the nanodepots can accelerate the growth of inorganic crystals and enhance the production of organic matrixes, synergistically facilitating the regeneration of bone defects in vivo. During the process, such a nanodepot can be constructed to specifically recognize osteoblasts for the monitoring of biomineralization. This nanoprobe represents an efficient strategy to promote and monitor biomineralization-related metabolic activities with applications in fundamental research, disease diagnosis, and regenerative medicine.

Objective: Polydopamine coated iron oxide nanoparticles (Fe3O4@PDA NPs) were synthesized, characterized, and their MR imaging contrast agents and photothermal potency were evaluated on melanoma (B16-F10 and A-375) cells and normal skin cells. To this end, MTT assay, Fe concentration, and MR imaging of both coated and uncoated NPs were assessed in C57BL/6 mice. Methods: Fe3O4 nanoparticles were synthesized using co-precipitation, and coated with polydopamine. The cytotoxicity of Fe3O4 and Fe3O4@PDA NPs on melanoma cells, with different concentrations, were obtained using MTT assay. MR images and Fe concentrations of nanoprobe and nanoparticles were evaluated under in vivo conditions. Results: Findings indicated that uncoated Fe3O4 showed the highest toxicity in animal (B16-F10) cells at 450μg/ml after 72h, while the highest toxicity in human (A-375) cells were observed at 350μg/ml. These nanoparticles did not reveal any cytotoxicity to normal skin cells, despite having some toxicity features in A-375 cells. MR image signals in the tumor were low compared with other tissues. The iron concentration in the tumor was higher than that of other organs. Conclusion: It is concluded that the cytotoxicity of Fe3O4@PDA was found to be significantly lower than uncoated nanoparticles (p

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.