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The combination of magnetic resonance and fluorescence imaging in dual‐modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH‐responsive magnetic resonance/near‐infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA‐Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA‐Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated‐enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA‐Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin‐binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA‐Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer. [ABSTRACT FROM AUTHOR]

MicroRNA‐21 (MiR‐21) has been confirmed to be upregulated in tumors, and its abnormal expression is closely associated with tumor occurrence. However, the traditional imaging methods are limited to qualitative imaging of miR‐21, and no effective strategy has been developed for monitoring its concentration in vivo during cancer initiation and progression. Herein, a biosensor is created utilizing a NIR‐II ratiometric fluorescent nanoprobe to quantitatively monitor dynamic alterations in miR‐21 levels in vivo. The nanoprobe (termed DCNP@DNA2@IR806) is constructed by introducing IR806 as a donor and down‐conversion nanoparticles (DCNP) as the acceptor, using DNA as linkers. Upon miR‐21‐responsive initiation of the nanoprobe, the 1550 nm fluorescent signal of DCNP stimulated by a 808 nm laser (F1550, 808Ex) increased because of the close proximity of IR806 to the DCNP and the subsequent non‐radiative energy transfer (NRET). Meanwhile, the 1550 nm fluorescent signal of DCNP stimulated by a 980 nm laser (F1550, 980Ex) remained stable because of the absence of NRET. This ratiometric NIR‐II fluorescent signal has been confirmed to be a reliable indicator of miR‐21 concentration in vivo. The strategy holds promise for further enhancing the understanding of microRNAs‐based molecular mechanisms underlying cancer progression, laying a foundation for the early diagnosis of microRNAs‐related diseases. [ABSTRACT FROM AUTHOR]

Fluorescence imaging with high spatiotemporal resolution and sensitivity is employed for in vivo visualization and detection applications. Compared with visible light and the first near-infrared window (700–900 nm), the second near-infrared window (1 000–1 700 nm) imaging has a lower auto-background fluorescence, deeper tissue penetration, and a higher signal-to-noise ratio, thus highlighting its broad prospects in the biomedical field. Currently, reported second near-infrared region probes include single-walled carbon nanotubes, rare-earth nanoparticles, quantum dots, metal materials, and organic molecular dyes. Multimodal imaging can overcome the limitations of single imaging and provide more comprehensive information on the anatomical structure, tissue composition, and cellular and molecular quantification of lesions to achieve multi-level visualization. Therefore, second near-infrared window nanoprobes must be engineered for multimodal imaging. Moreover, these nanoprobes can be actively targeted by modification with antibodies, peptides, nucleotides, or biofilms to obtain detailed and accurate information on biological systems. This review describes the active targeting capabilities of various second near-infrared window nanoprobes in multimodal imaging, diagnosis, and treatment of different diseases by carrying different ligands and the common features and future application prospects of second near-infrared window fluorescent nanoprobes with targeting ability.

In recent years, the deep integration of basic research and clinical translational research of nanotechnology and oncology has led to the emergence of a new branch, namely integrated nano-oncology. This is an emerging and important interdisciplinary field, which plays an irreplaceable role in the diagnosis, treatment, early warning, monitoring and prevention of tumors, and has become a new interdisciplinary frontier. Here main advances of integrated nano-oncology was reviewed, mainly included controlled preparation of nanomaterials, ultra-sensitive detection of tumor biomarkers, multi-functional nanoimaging probes and integrated diagnosis and treatment technology, innovative nano drugs and nano drug delivery system, DNA nanotechnology, RNA nanotechnology, nano self-assembly technology, nanosensors, intelligent nanorobots, nanotherapeutic machines. The terms, concepts, trends and challenges are also discussed with the aim of promoting the application of nanotechnology in integrated oncology and solving the scientific and key technical problems in basic and clinical translational research of cancer.

Airborne animal viral pathogens can rapidly spread and become a global threat, resulting in substantial socioeconomic and health consequences. To prevent and control potential epidemic outbreaks, accurate, fast, and affordable point-of-care (POC) tests are essential. As a proof-of-concept, we have developed a molecular system based on the loop-mediated isothermal amplification (LAMP) technique for avian metapneumovirus (aMPV) detection, an airborne communicable agent mainly infecting turkeys and chickens. For this purpose, a colorimetric system was obtained by coupling the LAMP technique with specific DNA-functionalized AuNPs (gold nanoparticles). The system was validated using 50 different samples (pharyngeal swabs and tracheal tissue) collected from aMPV-infected and non-infected chickens and turkeys. Viral detection can be achieved in about 60 min with the naked eye, with 100% specificity and 87.88% sensitivity for aMPV. In summary, this novel molecular detection system allows suitable virus testing in the field, with accuracy and limit of detection (LOD) values highly close to qRT-PCR-based diagnosis. Furthermore, this system can be easily scalable to a platform for the detection of other viruses, addressing the current gap in the availability of POC tests for viral detection in poultry farming. Key points: •aMPV diagnosis using RT-LAMP is achieved with high sensitivity and specificity. •Fifty field samples have been visualized using DNA-nanoprobe validation. •The developed system is a reliable, fast, and cost-effective option for POCT. [ABSTRACT FROM AUTHOR]

Chemiluminescence (CL) imaging, characterized by its high signal-to-noise ratio, has emerged as a highly promising approach for noninvasive and efficient tumor detection. Nevertheless, the development of efficient near-infrared (NIR) emission CL probes with good biocompatibility for precise tumor diagnosis remains a challenge. In the present study, we designed and synthesized a biocompatible NIR CL nanoparticle with aggregation-induced emission characteristics, named CPPO/BSA@AuNCs. Specifically, bis-(2,4,5-trichloro-6-carbopentoxyphenyl) oxalate (CPPO) was encapsulated by bovine serum albumin-capped gold nanoclusters (BSA@AuNCs) with aggregation-induced NIR emission properties. The nanoprobe demonstrated high CL signals with an extremely long lifetime and could be employed for quantitative analysis of reactive oxygen species, such as H2O2. Importantly, the NIR CL signal could effectively penetrate tissues with a penetration depth exceeding 27 mm, exhibiting significantly superior performance compared to the NIR fluorescence signal and blue CL signal. In vivo studies using mice bearing the 4T1 primary breast tumor and intraperitoneal metastases demonstrated that nanoprobe-based NIR CL imaging could effectively distinguish tumors from normal tissues, paving the way for CL-guided deep tumor diagnosis and surgery. [ABSTRACT FROM AUTHOR]

Electroanalysis is a type of analytical method used to study an analyte by measuring its electrical properties in an electrochemical cell. It has been widely used because it is a relatively simple and inexpensive technique, has a low detection limit and is able to measure original electrical signals. Electroanalysis has advanced with the development of nanotechnology, offering new opportunities for analysis. Scanning electrochemical microscopy (SECM) is a probe-based surface analysis instrument that enables real-time surface and interfacial analysis with spatial resolution in an electrochemical environment. In this review, we focus on the use of nanoscale SECM for improved electroanalysis. After introducing the fabrication, characterization, and modification of nanoelectrodes, which are the key to enabling nanoscale SECM, we introduce the instrumentation and fundamental principles of SECM. Several examples are provided to illustrate the advanced electroanalysis of photo-electrocatalysts and biosystems based on nanoscale SECM, which will be utilized as a more powerful electroanalytical tool in the future when combined with other analytical instruments.

Magnetic resonance imaging (MRI) is instrumental in the noninvasive evaluation of tumor tissues in patients subjected to chemotherapy, thereby yielding essential diagnostic data crucial for the prognosis of tumors and the formulation of therapeutic strategies. Currently, commercially available MRI contrast agents (CAs) predominantly consist of mononuclear gadolinium-(III) complexes. Because there is only one Gd-(III) atom per molecule, these CAs often require administration in high doses to achieve the desired contrast quality, which inevitably leads to some adverse events. Herein, we develop a six-nuclei, apoptosis-targeting T1 CA, Gd6–ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd6) with an apoptosis-targeting group (ZnDPA). The amplification of Gd-(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM–1 s–1, 1T) and low r1/r2 ratio (0.68, 1T). Based on the Solomon–Bloembergen–Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (τR). More importantly, the Gd6–ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (∼74%) and a long MRI imaging acquisition time window (∼48 h) in 4T1 tumor-bearing mice. This study introduces an experimental gadolinium-based CA for the potential imaging of tumor apoptosis in the context of MRI. [ABSTRACT FROM AUTHOR]

miRNAs (miRs) are short, noncoding RNA sequences that are present in biofluids such as blood, plasma, and serum. Their disrupted levels of expression correlate with different stages of various diseases, making them suitable as potential biomarkers. In this study, we present magnetic nanoprobes (MNPs) designed to capture specific target miRs (TmiRs) in biofluids like serum. The nanoprobes were formulated starting from PEGylated SPIONs using streptavidin–biotin interactions. The PEG chains were functionalized with complementary DNA sequence (cDNA-484) able to bind to TmiR-484, which is known to be overexpressed in serum of patients with colorectal cancer. The two-step formulation of the MNPs was monitored by SE-HPLC, following a previously established protocol. The colloidal stability of the MNPs and their ability to capture TmiR-484 were first determined in model solutions and then in human serum enriched with the commercially purchased TmiR-484. After magnetic sorting, the TmiR was released from the MNPs (dehybridization step) and quantified using qRT-PCR. [ABSTRACT FROM AUTHOR]

Ultra‐high field (UHF) magnetic resonance imaging (MRI) has emerged as a focal point of interest in the field of cancer diagnosis. Despite the ability of current paramagnetic or superparamagnetic smart MRI contrast agents to selectively enhance tumor signals in low‐field MRI, their effectiveness at UHF remains inadequate due to inherent magnetism. Here, we report a ligand‐mediated magnetism‐conversion nanoprobe (MCNP) composed of 3‐mercaptopropionic acid ligand‐coated silver‐gadolinium bimetallic nanoparticles. The MCNP exhibits a pH‐dependent magnetism conversion from ferromagnetism to diamagnetism, facilitating tunable nanomagnetism for pH‐activatable UHF MRI. Under neutral pH, the thiolate (−S−) ligands lead to short τ′m and increased magnetization of the MCNPs. Conversely, in the acidic tumor microenvironment, the thiolate ligands are protonated and transform into thiol (−SH) ligands, resulting in prolonged τ′m and decreased magnetization of the MCNP, thereby enhancing longitudinal relaxivity (r1) values at UHF MRI. Notably, under a 9 T MRI field, the pH‐sensitive changes in Ag−S binding affinity of the MCNP lead to a remarkable (>10‐fold) r1 increase in an acidic medium (pH 5.0). In vivo studies demonstrate the capability of MCNPs to amplify MRI signal of hepatic tumors, suggesting their potential as a next‐generation UHF‐tailored smart MRI contrast agent. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most common cause of dementia and a leading cause of mortality in the elderly population. Diagnosis of Alzheimer's disease has traditionally relied on evaluation of clinical symptoms for cognitive impairment with a definitive diagnosis requiring post‐mortem demonstration of neuropathology. However, advances in disease pathogenesis have revealed that patients exhibit Alzheimer's disease pathology several decades before the manifestation of clinical symptoms. Magnetic resonance imaging (MRI) plays an important role in the management of patients with Alzheimer's disease. The clinical availability of molecular MRI (mMRI) contrast agents can revolutionize the diagnosis of Alzheimer's disease. In this article, we review advances in nanoparticle contrast agents, also referred to as nanoprobes, for mMRI of Alzheimer's disease. This article is categorized under:Diagnostic Tools > In Vivo Nanodiagnostics and ImagingTherapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease [ABSTRACT FROM AUTHOR]

The focus of this review is on chitosan and the functionalization of chitosan nanoparticles using chlorotoxin as a targeting agent in drug delivery and treatment of glioma. Chitosan has been characterized as the most commonly used polymer for brain targeting with the highest bioadhesive and biocompatible properties. Chitosan is a long chain amino-polysaccharide polymer obtained by alkaline deacetylation of chitin polysaccharide, a natural component of crab shells. It was shown to have many beneficial properties such as antifungal, antibacterial, tissue repair or neuroprotective. The advantage of using chitosan-drug based delivery is that it is biodegradable, breaking down to amino acids, and is readily absorbed and safe to use. In addition, chitosan has mucoadhesive properties and affinity for MUC1 (CD227). This property of chitosan was evaluated by us previously in a chitosan based-drug delivery system to tumor cells. Chitosan has been evaluated as a vehicle for various drug delivery systems including those for glioma and glioblastoma cells.Glioma is a highly aggressive and invasive brain tumor with low patient's survival and currently no effective therapies beside the standard surgery, radiation and chemotherapy. Chlorotoxin is a 36 amino acids peptide and originally purified from venom of scorpion Leiurus quinquestriatus. It can be synthetically manufactured and was first shown to have an affinity for neuroectodermal tumor cells and later also for several other types of tumors. It has been shown to target tumor cells such as glioma in vitro and in vivo as well as in clinical studies. Conjugated to 131-I and administered intravenously its tumor targeting properties were evaluated in clinical trials treating glioblastoma. Recently, chlorotoxin has been applied in models of tumor detection and drug delivery systems including polymeric nanoparticles with chitosan to functionalize their delivery specifically to glioma.

The past two decades have witnessed breakthroughs in cellular‐scale bioelectronics and their widespread applications in life sciences, creating many powerful platforms for studying organisms directly and efficiently. These advanced devices can integrate seamlessly and intimately onto/into target cells and organoids, providing unprecedented functions and revolutionary capabilities. Bioelectronics with nanostructured designs are developed to allow for long‐term, stable monitoring of electrophysiological activities. This review summarizes nanostructured bioelectronics for cell electrophysiology recording, emphasizing the crucial roles of structural designs on functions and capabilities, e.g., intracellular access, high‐density multiplexed recording, multifunctional interfaces and the conformability to curvy biological shapes. Finally, the remaining challenges and opportunities in nanostructured bioelectronics are identified, and perspectives on the future developments toward their practical applications are provided. [ABSTRACT FROM AUTHOR]

Currently, spatiotemporal theranostic nanoprobes are in great demand, owing to their enhanced target therapy and precise dynamic tracing of in vivo drug fate. Herein, this study highlights the successful development of dynamic theranostic nanoprobes, which are facilely established via self‐assembly between glutathione (GSH)‐responsive dasatinib (DAS) dimers and indocyanine green (ICG). The DAS dimers endow the nanoprobes with aggregation‐induced emission (AIE) characteristic, whose emission wavelength successfully redshifts from 420 to 810 nm compared to DAS‐based nanoprobes, the same as that of ICG, thus improving the total fluorescence intensity. Moreover, the nanoprobes exhibit a dynamic fluorescence intensity conversion that first decreases and then increases at the tumor site via intracellular GSH‐triggered AIE quenching and fluorescence re‐enhancement of ICG, therefore achieving precise tumor diagnosis, prognosis evaluation, and spatiotemporal tracing of drug fate compared to other imaging strategies. Furthermore, the nanoprobes show long‐term circulation stability via suitable particle sizes and zeta potentials, improved tumor accumulation via extracellular protonation and active cellular uptake, efficient drug release via response to the intracellular milieu, and enhanced apoptosis via targeting to intracellular kinase, therefore achieving the significant tumor inhibition. Thus, the spatiotemporal theranostic nanoprobes can dynamically monitor the targeted tumor therapy, greatly advancing their application in clinics. [ABSTRACT FROM AUTHOR]

Abstract Immunoassay is a powerful technique that uses highly specific antigen‐antibody interactions to detect biochemical targets such as proteins and toxins. As a diagnostic tool, immunoassay is employed in the screening, diagnosis, and prognosis of diseases, which are crucial for the grasp and control of patient conditions in clinical practice. With the rapid development of nanotechnology, immunoassays based on nanoprobes have attracted more and more attention due to the advantages of high sensitivity, specificity, stability, and versatility. These nanoprobes are nanoscale particles that can act as signal carriers or targeting agents for immunoassays. In this paper, we review the recent advances in various types of nanoprobes for immunoassays, such as colloidal gold, quantum dots, magnetic nanoparticles, nanozymes, aggregation‐induced emission, and up‐conversion nanoparticles. The effect of the nanoprobe construction and synthesis methods on their detection performance deserves to be studied in depth. We also compare their detection ranges and limits in different immunoassay methods, such as lateral flow immunoassays, fluorescent immunoassays, and surface‐enhanced Raman scattering immunoassays. Moreover, we discuss the benefits and challenges of nanoprobes in immunoassays and provide insights into their future development. This study aims to offer a comprehensive and critical perspective on the role of nanoprobes in the field of immunoassays.

Abstract The past two decades have witnessed breakthroughs in cellular‐scale bioelectronics and their widespread applications in life sciences, creating many powerful platforms for studying organisms directly and efficiently. These advanced devices can integrate seamlessly and intimately onto/into target cells and organoids, providing unprecedented functions and revolutionary capabilities. Bioelectronics with nanostructured designs are developed to allow for long‐term, stable monitoring of electrophysiological activities. This review summarizes nanostructured bioelectronics for cell electrophysiology recording, emphasizing the crucial roles of structural designs on functions and capabilities, e.g., intracellular access, high‐density multiplexed recording, multifunctional interfaces and the conformability to curvy biological shapes. Finally, the remaining challenges and opportunities in nanostructured bioelectronics are identified, and perspectives on the future developments toward their practical applications are provided.

Recent advances in molecular technologies have provided various assay strategies for monitoring biomarkers, such as miRNAs for early detection of various diseases and cancers. However, there is still an urgent unmet need to develop practical and accurate miRNA analytical tools that could facilitate the incorporation of miRNA biomarkers into clinical practice and management. In this study, we demonstrate the feasibility of using a cascade amplification method, referred to as the "Cascade Amplification by Recycling Trigger Probe" (CARTP) strategy, to improve the detection sensitivity of the inverse Molecular Sentinel (iMS) nanobiosensor. The iMS nanobiosensor developed in our laboratory is a unique homogeneous multiplex bioassay technique based on surface-enhanced Raman scattering (SERS) detection, and was used to successfully detect miRNAs from clinical samples. The CARTP strategy based on the toehold-mediated strand displacement reaction is triggered by a linear DNA strand, called the "Recycling Trigger Probe" (RTP) strand, to amplify the iMS SERS signal. Herein, by using the CARTP strategy, we show a significantly improved detection sensitivity with the limit of detection (LOD) of 45 fM, which is 100-fold more sensitive than the non-amplified iMS assay used in our previous report. We envision that the further development and optimization of this strategy ultimately will allow multiplexed detection of miRNA biomarkers with ultra-high sensitivity for clinical translation and application. [ABSTRACT FROM AUTHOR]

The worldwide pollution of water bodies by potential contaminants such as heavy metals, dyes, and pesticides etc. have severely affected the entire eco-system due to their toxic mobility and tough degradation in water. Consequently, there is a requirement to develop cost-competitive and easily handleable sensing materials which can detect targets sensitively and with selectivity. Among the low-cost sensory materials, carbon dots (CDs) constitute an important class of carbon nanomaterial with unique photostability, electronic and fluorescent properties. This review is an effort to comprehend the recent improvements in the sensing applications of CDs with prominence on synthetic routes, the effect of various synthesis parameters on physical properties (quantum yield, size range), detection mechanisms, and detection parameters (limit of detection, interference etc.). Particularly, the scope and progress for the detection of potential water contaminants using CDs have been explored and a holistic view of mechanisms of their detection has been included. Holistic view of mechanisms for different types of signals generated by CDs. [ABSTRACT FROM AUTHOR]

Abstract Almost all physiological processes of animals are controlled by the brain, including language, cognitive, memory, learning, emotion and so forth. Minor brain dysfunction usually leads to brain diseases and disorders. Therefore, it' is greatly meaningful and urgent for scientists to have a better understanding of brain structure and function. Optical approaches can provide powerful tools for imaging and modulating physiological processes of the brain. In particular, optical approaches in the near‐infrared (NIR) window (700–1700 nm) exhibit excellent prosperities of deep tissue penetration and low tissue scattering and absorption compared with those of visible windows (400–700 nm), which provides a promising approach for scientists to develop desired methods of neuroimaging and neuromodulation in deep brain tissues. In this review, variable types of NIR light approaches for imaging and modulating neural ions, membrane potential, neurotransmitters, and other critical molecules for brain functions and diseases are summarized. In particular, the latest breakthrough research of brain imaging and brain regulation in the NIR‐II window (1000–1700 nm) are highlighted. Finally, we conclude the challenges and prospects of NIR light‐based neuroimaging and neuromodulation for both basic brain research and further clinical translation.

As an important component of the tumor immune microenvironment (TIME), tumor-associated macrophages (TAMs) occupy a significant niche in tumor margin aggregation and respond to changes in the TIME. Thus, targeting TAMs is important for tumor monitoring, surgical guidance and efficacy evaluation. Continuously developing nanoprobes and imaging agents paves the way toward targeting TAMs for precise imaging and diagnosis. This review summarizes the commonly used nanomaterials for TAM targeting imaging probes, including metal-based nanoprobes (iron, manganese, gold, silver), fluorine-19-based nanoprobes, radiolabeled agents, near-infrared fluorescence dyes and ultrasonic nanobubbles. Additionally, the prospects and challenges of designing nanomaterials for imaging and diagnosis (targeting efficiency, pharmacokinetics, and surgery guidance) are described in this review. Notwithstanding, TAM-targeting nanoplatforms provide great potential for imaging, diagnosis and therapy with a greater possibility of clinical transformation. [ABSTRACT FROM AUTHOR]

In this study, luminescent bio-adsorbent nitrogen-doped carbon dots (N-CDs) was produced and applied for the removal and detection of Hg (II) from aqueous media. N-CDs were synthesized from oil palm empty fruit bunch carboxymethylcellulose (CMC) and urea. According to several analytical techniques used, the obtained N-CDs display graphitic core with an average size of 4.2 nm, are enriched with active sites, stable over a wide range of pH and have great resistance to photobleaching. The N-CDs have bright blue emission with an improved quantum yield (QY) of up to 35.5%. The effect of the variables including pH, adsorbent mass, initial concentration and incubation time on the removal of Hg (II) was investigated using central composite design. The statistical results confirmed that the adsorption process could reach equilibrium within 30 min. The reduced cubic model (R2 = 0.9989) revealed a good correlation between the observed values and predicted data. The optimal variables were pH of 7, dose of 0.1 g, initial concentration of 100 mg/L and duration of 30 min. Under these conditions, adsorption efficiency of 84.6% was obtained. The adsorption kinetic data could be well expressed by pseudo-second-order kinetic and Langmuir isotherm models. The optimal adsorption capacity was 116.3 mg g−1. Furthermore, the adsorbent has a good selectivity towards Hg (II) with a detection limit of 0.01 μM due to the special interaction between Hg (II) and carboxyl/amino groups on the edge of N-CDs. This work provided an alternative direction for constructing low-cost adsorbents with effective sorption and sensing of Hg (II). [ABSTRACT FROM AUTHOR]

Nucleic acid aptamers have attracted much interest in the bioanalytical field and have been employed to construct aptamer-based sensors (aptasensors) for the determination of multifarious disease biomarkers, attributing to their prominent advantages, such as good chemical and thermodynamic stability, ease of synthesis, utilization, and low cost. Along with acquisition of more and more effective aptamers, numerous aptasensors have been developed with many techniques, including UV-Vis (colorimetry), fluorescence, surface-enhanced Raman scattering, chemiluminescence/electrochemiluminescence, and electrochemical methods, and various types of biomarkers were detected, such as cardiac troponin I, carcinoembryonic antigen, and C-reactive protein, etc. Through overviewing these related typical works, this minireview aims to reveal effective approaches to high sensitivity, for example, DNA-based amplification and nanoprobe design, point out critical issues that impede the further practical use, and hopefully contribute to the development of aptasensors in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • Summarizing the research progress in fluorescent probes towards biological NO for diagnosis. • The aim is to better understand the sensing mechanism of nitric oxide by fluorescent probes with different reaction mechanisms and to provide some references for the design of novel fluorescent probes. Nitric oxide (NO) plays an important role in multiple physiological processes of the body involved in regulation, such as cardiovascular relaxation, neural homeostasis, and immune regulation, etc. The real-time monitoring of NO is of great significance in the investigation of related disease mechanisms and the evaluation of pharmacodynamics. Fluorescent probes are considered as a highly promising approach for pharmaceutical analysis and bioimaging due to their non-invasive character, real-time detection, and high sensitivity. However, there are still some challenges in the determination of biological nitric oxide with fluorescent probes, such as low anti-interference ability, poor function modifiability, and low organ specificity. Therefore, it would be beneficial to develop a new generation of fluorescent probes for real-time bioimaging of NO in vivo after this systematic summary. [ABSTRACT FROM AUTHOR]

Schematic illustration of the manufacturing process of the bioprobes and dynamical monitoring of "immune-vascular crosstalk" changing processes via multi-functional MRI. [Display omitted] • Identify varying PTT levels to set positive/negative tumor immune-vascular crosstalk status. • Sensitively multi-functional MR imaging normalized/ablated tumor vascular status. • Imaging-guided vascular status uncover underlying tumor immune environments status. • Pathology-based monitoring positive/negative IVC loop via functional MRI-guided. Immunotherapy holds significant promise to completely eliminate tumor, yet lack of timely evaluation of immune responses, which challenged by inherent lagging and pseudoprogression during immunotherapy. Immune-vascular crosstalk (IVC), an enhancement ring for the mutual regulation linking tumor vascular normalization with immune remodeling forms, emerging as a systematic indicator for immunotherapy outcomes, necessitates timely, non-invasive, and early detection of its status to enhance clinical benefits. Herein, positive and negative loop models of tumor IVC were established using different degree of photothermal therapy (PTT) based on NaBiF 4 :Gd@PDA@PEG nanoprobes. Multi-functional magnetic resonance imaging, including fast spoiled gradient-recalled (FSPGR), time-resolved imaging of contrast kinetics (TRICKs) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), was applied to dynamically reflect normalized/ablated tumor vasculature, well-matched increased/decreased immune response corresponding to different status of IVC, confirmed by pathology results. This study proposes a novel biological method to noninvasively detect the positive/negative IVC loop, paving the visualized way for immunotherapy assessed benefits, which is expected to be extended to clinical translation. [ABSTRACT FROM AUTHOR]

The field of second near-infrared (NIR-II) surface-enhanced Raman scattering (SERS) nanoprobes has made commendable progress in biomedicine. This article reviews recent advances and future development of NIR-II SERS nanoprobes. It introduces the fundamental principles of SERS nanoprobes and highlights key advances in the NIR-II window, including reduced tissue attenuation, deep penetration, maximized allowable exposure, and improved photostability. The discussion of future directions includes the refinement of nanoprobe substrates, emphasizing the tailoring of optical properties of metallic SERS-active nanoprobes, and exploring non-metallic alternatives. The intricacies of designing Raman reporters for the NIR-II resonance and the potential of these reporters to advance the field are also discussed. The integration of artificial intelligence (AI) into nanoprobe design represents a cutting-edge approach to overcome current challenges. This article also examines the emergence of deep Raman techniques for through-tissue SERS detection, toward NIR-II SERS tomography. It acknowledges instrumental advancements like improved charge-coupled device sensitivity and accelerated imaging speeds. The article concludes by addressing the critical aspects of biosafety, ease of functionalization, compatibility, and the path to clinical translation. With a comprehensive overview of current achievements and future prospects, this review aims to illuminate the path for NIR-II SERS nanoprobes to innovate diagnostic and therapeutic approaches in biomedicine., (© 2024 Wiley‐VCH GmbH.)

NIR-II imaging has the advantages of high sensitivity, spatiotemporal resolution, and high penetration depth, thereby serving as a potential alternative to conventional imaging methods. Herein, a novel NIR-II dye IR-1010 (λ ex /λ em = 1010/1058 nm) is reported with high quantum yield (3.08%) and good stability, by incorporating p-methoxyphenyl groups into a quinolinium cyanine dye. Then a multifunctional nanoprobe, termed IUFP NPs, is developed by the incorporation of upconversion (UC) nanoparticles (NPs), perfluoro-15-crown-5-ether (PFCE), and IR-1010, to display the novel performance of multimodal imaging. Under the single-wavelength excitation (980 nm), IUFP NPs simultaneously emit the NIR-II fluorescence of IR-1010 and visible UC luminescence of UCNPs, and thus realize the UC imaging for cells, and NIR-II fluorescence/photoacoustic/ 19 F magnetic resonance imaging for blood vessels, lymph nodes and tumor in mice. This work affords a novel approach to NIR-II dyes and a general strategy for the design of multimodal imaging probes., (© 2024 Wiley‐VCH GmbH.)

Targeted imaging of cancer lymphatic metastasis remains challenging due to its highly heterogeneous molecular and phenotypic diversity. Herein, triple-targeted protein nanoprobes capable of specifically binding to three targets for imaging cancer lymphatic metastasis, through a data-driven design approach combined with a synthetic biology-based assembly strategy, are introduced. Specifically, to address the diversity of metastatic lymph nodes (LNs), a combination of three targets, including C-X-C motif chemokine receptor 4 (CXCR4), transferrin receptor protein 1 (TfR1), and vascular endothelial growth factor receptor 3 (VEGFR3) is identified, leveraging machine leaning-based bioinformatics analysis and examination of LN tissues from patients with gastric cancer. Using this identified target combination, ferritin nanocage-based nanoprobes capable of specifically binding to all three targets are designed through the self-assembly of genetically engineered ferritin subunits using a synthetic biology approach. Using these nanoprobes, multiplexed imaging of heterogeneous metastatic LNs is successfully achieved in a polyclonal lymphatic metastasis animal model. In 19 freshly resected human gastric specimens, the signal from the triple-targeted nanoprobes significantly differentiates metastatic LNs from benign LNs. This study not only provides an effective nanoprobe for imaging highly heterogeneous lymphatic metastasis but also proposes a potential strategy for guiding the design of targeted nanomedicines for cancer lymphatic metastasis., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Recent advances in molecular technologies have provided various assay strategies for monitoring biomarkers, such as miRNAs for early detection of various diseases and cancers. However, there is still an urgent unmet need to develop practical and accurate miRNA analytical tools that could facilitate the incorporation of miRNA biomarkers into clinical practice and management. In this study, we demonstrate the feasibility of using a cascade amplification method, referred to as the “Cascade Amplification by Recycling Trigger Probe” (CARTP) strategy, to improve the detection sensitivity of the inverse Molecular Sentinel (iMS) nanobiosensor. The iMS nanobiosensor developed in our laboratory is a unique homogeneous multiplex bioassay technique based on surface-enhanced Raman scattering (SERS) detection, and was used to successfully detect miRNAs from clinical samples. The CARTP strategy based on the toehold-mediated strand displacement reaction is triggered by a linear DNA strand, called the “Recycling Trigger Probe” (RTP) strand, to amplify the iMS SERS signal. Herein, by using the CARTP strategy, we show a significantly improved detection sensitivity with the limit of detection (LOD) of 45 fM, which is 100-fold more sensitive than the non-amplified iMS assay used in our previous report. We envision that the further development and optimization of this strategy ultimately will allow multiplexed detection of miRNA biomarkers with ultra-high sensitivity for clinical translation and application.

The chemical microenvironment in cells is extremely complex involving numerous species with drastically different concentration as well as temporal and spatial distribution. Especially, reactive species including ROS, RNS, RSS, and many inorganic ions are recognized to play very important roles. The concentrations of these species are constantly regulated and often depend on each other. While fluorescent probes have been widely used to study various cell biological processes, those simultaneously probing two species just emerged recently. In this review, we highlight dual-functional luminescent probes for the detection and fluorescence imaging of two and more analytes in cells. The content will cover small-molecule synthetic fluorescent probes, DNA nanoassemblies, and nanoparticle-based nanoprobes. The target analytes include reactive species such as ROS, RNS, and RSS and other ions and molecules such as H+, Cl-, Ca2+, Cu2+, and O2. [ABSTRACT FROM AUTHOR]