Catalytic Dual-Mode Immunotherapy: Anisotropic AuPt Heterostructure Decorated with Starry Pt Nanoclusters for Robust Cancer Photometalloimmunotherapy.

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.

Developmental Prediction of Poststroke Patients in Activities of Daily Living by Using Tree-Structured Parzen Estimator-Optimized Stacking Ensemble Approaches.

Poststroke injuries limit the daily activities of patients and cause considerable inconvenience. Therefore, predicting the activities of daily living (ADL) results of patients with stroke before hospital discharge can assist clinical workers in formulating more personalized and effective strategies for therapeutic intervention, and prepare hospital discharge plans that suit the patients needs. This study used the leave-one-out cross-validation procedure to evaluate the performance of the machine learning models. In addition, testing methods were used to identify the optimal weak learners, which were then combined to form a stacking model. Subsequently, a hyperparameter optimization algorithm was used to optimize the model hyperparameters. Finally, optimization algorithms were used to analyze each feature, and features of high importance were identified by limiting the number of features to be included in the machine learning models. After various features were fed into the learning models to predict the Barthel index (BI) at discharge, the results indicated that random forest (RF), adaptive boosting (AdaBoost), and multilayer perceptron (MLP) produced suitable results. The most critical prediction factor of this study was the BI at admission. Machine learning models can be used to assist clinical workers in predicting the ADL of patients with stroke at hospital discharge.

An artificial protein modulator reprogramming neuronal protein functions.

Reversible protein phosphorylation, regulated by protein phosphatases, fine-tunes target protein function and plays a vital role in biological processes. Dysregulation of this process leads to aberrant post-translational modifications (PTMs) and contributes to disease development. Despite the widespread use of artificial catalysts as enzyme mimetics, their direct modulation of proteins remains largely unexplored. To address this gap and enable the reversal of aberrant PTMs for disease therapy, we present the development of artificial protein modulators (APROMs). Through atomic-level engineering of heterogeneous catalysts with asymmetric catalytic centers, these modulators bear structural similarities to protein phosphatases and exhibit remarkable ability to destabilize the bridging µ3-hydroxide. This activation of catalytic centers enables spontaneous hydrolysis of phospho-substrates, providing precise control over PTMs. Notably, APROMs, with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein by directly hydrolyzing hyperphosphorylated α-synuclein. Consequently, synaptic function is reinforced in Parkinson's disease. Our findings offer a promising avenue for reprogramming protein function through de novo PTMs strategy.

Self-propelled assembly of nanoparticles with self-catalytic regulation for tumour-specific imaging and therapy.

Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.

A Cancer Cell Selective Replication Stress Nano Amplifier Promotes Replication Fork Catastrophe to Overcome Radioresistance.

Replication stress (RS) induced by DNA damage plays a significant role in conferring the anticancer effects of radiotherapy and is tightly associated with radioresistance of cancer cells. Amplification of RS represents an effective approach to improving the efficacy of radiotherapy, although the development of selective RS amplifiers remains an unexplored frontier. We herein present an RS nano amplifier (RSNA) consisting of a catalytic FePt nanoparticle loaded with the chemotherapeutic doxorubicin (DOX), which selectively exacerbates RS in cancer cells by promoting replication fork (RF) catastrophe. RSNA converts the excessive reactive oxygen species (ROS) in cancer cells into oxygen, enhancing the DNA-damaging effects of radiotherapy to create more template lesions that impede RF progression in coalition with DOX. After radiation, ROS scavenging by RSNA accelerates RF progression through damaged template strands, increasing the frequency of RF collapse into double-strand breaks. Moreover, pretreatment with RSNA accumulates cancer cells in the S phase, exposing more RFs to radiation-induced RS. These effects of RSNA convergently maximize RS in cancer cells, effectively overcoming the radioresistance of cancer cells without affecting normal cells. Our study demonstrates the feasibility of selectively amplifying RS to boost radiotherapy.

Nanozyme-Integrated Thermoresponsive In Situ Forming Hydrogel Enhances Mesenchymal Stem Cell Viability and Paracrine Effect for Efficient Spinal Cord Repair.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising strategy for the treatment of spinal cord injury (SCI). However, the hostile microenvironment of SCI, which can adversely affect the survival and paracrine effect of the implanted MSCs, severely limits the therapeutic efficacy of this approach. Here, we report on a ceria nanozyme-integrated thermoresponsive in situ forming hydrogel (CeNZ-gel) that can enable dual enhancement of MSC viability and paracrine effect, leading to highly efficient spinal cord repair. The sol-gel transition property of the CeNZ-gel at body temperature ensures uniform coverage of the hydrogel in injured spinal cord tissues. Our results demonstrate that the CeNZ-gel significantly increases the viability of transplanted MSCs in the microenvironment by attenuating oxidative stress and, more importantly, promotes the secretion of angiogenic factors from MSCs by inducing autophagy of MSCs. The synergy between the oxidative stress-relieving effect of CeNZs and the paracrine effect of MSCs accelerates angiogenesis, nerve repair, and motor function recovery after SCI, providing an efficient strategy for MSC-based SCI therapy.

Ensemble learning based functional independence ability estimator for pediatric brain tumor survivors.

A history of brain tumor strongly affects children's cognitive abilities, performance of daily activities, quality of life, and functional outcomes. In light of the difficulties in cognition, communication, physical skills, and behavior that these patients may encounter, occupational therapists should perform a comprehensive needs-led assessment of their global functioning after recovery. Such an assessment would ensure that the patients receive adequate support and services at school, at home, and in the community. By predicting the functional activity performance of children with a history of brain tumor, clinical workers can determine the progress of their ability recovery and the optimal treatment plan. We selected several features for testing and employed common machine learning models to predict Functional Independence Measure (WeeFIM) scores. The ensemble learning models exhibited stronger predictive performance than did the individual machine learning models. The ensemble learning models effectively predicted WeeFIM scores. Machine learning models can help clinical workers predict the functional assessment scores of patients with childhood brain tumors. This study used machine learning models to predict the WeeFIM scores of patients with childhood brain tumors and to demonstrate that ensemble machine learning models are more suitable for this task than are individual machine learning models.

Protective Effects of Epigallocatechin Gallate for Male Sexual Dysfunction in Streptozotocin-Induced Diabetic Rats.

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.

A K+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification.

Although molecular imaging probes have the potential to non-invasively diagnose a tumor, imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain elusive. Here, we demonstrate a potassium ion (K+) sensitive dual-mode nanoprobe (KDMN) for non-invasive tumor imaging and malignancy identification, which operates via a cascaded 'AND' logic gate controlled by inputs of magnetic resonance imaging (MRI) and fluorescence imaging (FI) signals. We encapsulate commercial K+ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles, which are subsequently coated with a K+-selective membrane that exclusively permits the passage of K+ while excluding other cations. The KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic administration. Spatial information of the tumor lesion is thus accessible via MRI and forms the first layer of the 'AND' gate. Meanwhile, the KDMN selectively captures K+ and prevents interference from other cations, triggering a K+-activated FI signal as the second layer of the 'AND' gate in the case of a malignant tumor with a high extracellular K+ level. This dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.

Ultrasmall Ruthenium Nanoparticles with Boosted Antioxidant Activity Upregulate Regulatory T Cells for Highly Efficient Liver Injury Therapy.

Nanozymes exhibiting antioxidant activity are beneficial for the treatment of oxidative stress-associated diseases. Ruthenium nanoparticles (RuNPs) with multiple enzyme-like activities have attracted growing attention, but the relatively low antioxidant enzyme-like activities hinder their practical biomedical applications. Here, a size regulation strategy is presented to significantly boost the antioxidant enzyme-like activities of RuNPs. It is found that as the size of RuNPs decreases to ≈2.0 nm (sRuNP), the surface-oxidized Ru atoms become dominant, thus possessing an unprecedentedly boosted antioxidant activity as compared to medium-sized (≈3.9 nm) or large-sized counterparts (≈5.9 nm) that are mainly composed of surface metallic Ru atoms. Notably, based on their antioxidant enzyme-like activities and ultrasmall size, sRuNP can not only sustainably ameliorate oxidative stress but also upregulate regulatory T cells in late-stage acetaminophen (APAP)-induced liver injury (ALI). Consequently, sRuNPs perform highly efficient therapeutic efficiency on ALI mice even when treated at 6 h after APAP intoxication. This strategy is insightful for tuning the catalytic performances of nanozymes for their extensive biomedical applications.

Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy.

Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. HLX10, a fully humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro, and anti-tumor activity in several tumor models. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. To elucidate HLX10's mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. Notably, HLX10's epitope was closer to Pembrolizumab's epitope than Nivolumab's epitope. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo, providing a rationale for clinical evaluation in cancer immunotherapy.

Distinguishing features of a novel humanized anti-EGFR monoclonal antibody based on cetuximab with superior antitumor efficacy.

BACKGROUND: Cetuximab, the first approved EGFR targeting therapeutic antibody, is currently used to treat colorectal cancer and head and neck cancer. While effective, cetuximab is associated with a higher rate of skin rash, infusion reactions, and gastrointestinal toxicity, which was suggested to be linked to the presence of heterogeneous glycan contents on the Fab of the SP2/0-produced cetuximab. OBJECTIVE AND METHODS: To improve efficacy and minimize toxicity of EGFR inhibition treatment, we re-engineered cetuximab by humanizing its Fab regions and minimizing its glycan contents to generate HLX07. RESULTS: HLX07 binds to EGFR with similar affinity as cetuximab and shows better bioactivity compared to cetuximab in vitro. In vivo studies demonstrated that HLX07 significantly inhibited the growth of A431, FaDu, NCI-H292, and WiDr tumor cells and synergized them with chemotherapeutics and immune simulator agents such as anti-PD-1. In cynomolgus monkeys, 13-week repeat-dose GLP toxicokinetic studies showed minimal-to-mild toxicities in the dose range of up to 60 mg/kg/wk. In the preliminary phase 1 dose-escalation study, HLX07 had showed lower incidence of skin rashes with grade >2 severities. CONCLUSION: HLX07 is currently under phase 1/2 clinical development. We believe HLX07 would potentially be an alternative for patients who have been suffering from cetuximab-mediated toxicity.

Dynamic nanoassemblies for imaging and therapy of neurological disorders.

The past decades have witnessed an increased incidence of neurological disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, and epilepsy, which significantly lower patients' life quality and increase the economic and social burden. Recently, nanomedicines composed of imaging and/or therapeutic agents have been explored to diagnose and/or treat NDs due to their enhanced bioavailability, blood-brain barrier (BBB) permeability, and targeting capacity. Intriguingly, dynamic nanoassemblies self-assembled from functional nanoparticles to simultaneously interfere with multiple pathogenic substances and pathological changes, have been regarded as one of the foremost candidates to improve the diagnostic and therapeutic efficacy of NDs. To help readers better understand this emerging field, in this review, the pathogenic mechanism of different types of NDs is briefly introduced, then the functional nanoparticles used as building blocks in the construction of dynamic nanoassemblies for NDs theranostics are summarized. Furthermore, dynamic nanoassemblies that can actively cross the BBB to target brain lesions, sensitively and efficiently diagnose or treat NDs, and effectively promote neuroregeneration are highlighted. Finally, we conclude with our perspectives on the future development in this field.

Dynamic nanoassembly-based drug delivery system (DNDDS): Learning from nature.

Dynamic nanoassembly-based drug delivery system (DNDDS) has evolved from being a mere curiosity to emerging as a promising strategy for high-performance diagnosis and/or therapy of various diseases. However, dynamic nano-bio interaction between DNDDS and biological systems remains poorly understood, which can be critical for precise spatiotemporal and functional control of DNDDS in vivo. To deepen the understanding for fine control over DNDDS, we aim to explore natural systems as the root of inspiration for researchers from various fields. This review highlights ingenious designs, nano-bio interactions, and controllable functionalities of state-of-the-art DNDDS under endogenous or exogenous stimuli, by learning from nature at the molecular, subcellular, and cellular levels. Furthermore, the assembly strategies and response mechanisms of tailor-made DNDDS based on the characteristics of various diseased microenvironments are intensively discussed. Finally, the current challenges and future perspectives of DNDDS are briefly commented.

Microenvironment-tailored nanoassemblies for the diagnosis and therapy of neurodegenerative diseases.

Neurodegenerative disorder is an illness involving neural dysfunction/death attributed to complex pathological processes, which eventually lead to the mortality of the host. It is generally recognized through features such as mitochondrial dysfunction, protein aggregation, oxidative stress, metal ions dyshomeostasis, membrane potential change, neuroinflammation and neurotransmitter impairment. The aforementioned neuronal dysregulations result in the formation of a complex neurodegenerative microenvironment (NME), and may interact with each other, hindering the performance of therapeutics for neurodegenerative disease (ND). Recently, smart nanoassemblies prepared from functional nanoparticles, which possess the ability to interfere with different NME factors, have shown great promise to enhance the diagnostic and therapeutic efficacy of NDs. Herein, this review highlights the recent advances of stimuli-responsive nanoassemblies that can effectively combat the NME for the management of ND. The first section outlined the NME properties and their interrelations that are exploitable for nanoscale targeting. The discussion is then extended to the controlled assembly of functional nanoparticles for the construction of stimuli-responsive nanoassemblies. Further, the applications of stimuli-responsive nanoassemblies for the enhanced diagnosis and therapy of ND are introduced. Finally, perspectives on the future development of NME-tailored nanomedicines are given.

A Phosphatase-Mimetic Nano-Stabilizer of Mast Cells for Long-Term Prevention of Allergic Disease.

Allergic diseases are pathological immune responses with significant morbidity, which are closely associated with allergic mediators as released by allergen-stimulated mast cells (MCs). Prophylactic stabilization of MCs is regarded as a practical approach to prevent allergic diseases. However, most of the existing small molecular MC stabilizers exhibit a narrow therapeutic time window, failing to provide long-term prevention of allergic diseases. Herein, ceria nanoparticle (CeNP-) based phosphatase-mimetic nano-stabilizers (PMNSs) with a long-term therapeutic time window are developed for allergic disease prevention. By virtue of the regenerable catalytic hotspots of oxygen vacancies on the surface of CeNPs, PMNSs exhibit sustainable phosphatase-mimetic activity to dephosphorylate phosphoproteins in allergen-stimulated MCs. Consequently, PMNSs constantly modulate intracellular phospho-signaling cascades of MCs to inhibit the degranulation of allergic mediators, which prevents the initiation of allergic mediator-associated pathological responses, eventually providing protection against allergic diseases with a long-term therapeutic time window.

Chemical design of nanozymes for biomedical applications.

With the advancement of nanochemistry, artificial nanozymes with high catalytic stability, low manufacturing and storage cost, and greater design flexibility over natural enzymes, have emerged as a next-generation nanomedicine. The catalytic activity and selectivity of nanozymes can be readily controlled and optimized by the rational chemical design of nanomaterials. This review summarizes the various chemical approaches to regulate the catalytic activity and selectivity of nanozymes for biomedical applications. We focus on the in-depth correlation between the physicochemical characteristics and catalytic activities of nanozymes from several aspects, including regulating chemical composition, controlling morphology, altering the size, surface modification and self-assembly. Furthermore, the chemically designed nanozymes for various biomedical applications such as biosensing, infectious disease therapy, cancer therapy, neurodegenerative disease therapy and injury therapy, are briefly summarized. Finally, the current challenges and future perspectives of nanozymes are discussed from a chemistry point of view. STATEMENT OF SIGNIFICANCE: As a kind of nanomaterials that performs enzyme-like properties, nanozymes perform high catalytic stability, low manufacturing and storage cost, attracting the attention of researchers from various fields. Notably, chemically designed nanozymes with robust catalytic activity, tunable specificity and multi-functionalities are promising for biomedical applications. It's crucial to define the correlation between the physicochemical characteristics and catalytic activities of nanozymes. To help readers understand this rapidly expanding field, in this review, we summarize various chemical approaches that regulate the catalytic activity and selectivity of nanozymes together with the discussion of related mechanisms, followed by the introduction of diverse biomedical applications using these chemically well-designed nanozymes. Hopefully our review will bridge the chemical design and biomedical applications of nanozymes, supporting the extensive research on high-performance nanozymes.

Applications of ion level nanosensors for neuroscience research.

Ion activities are tightly associated with brain physiology, such as intracranial cell membrane potential, neural activity and neuropathology. Thus, monitoring the ion levels in the brain is of great significance in neuroscience research. Recently, nanosensors have emerged as powerful tools for monitoring brain ion levels and dynamics. With controllable structures and functions, nanosensors have been intensively used for monitoring neural activity and cell function and can be used in disease diagnosis. Here, we summarize the recent advances in the design and application of ion level nanosensors at different physiological levels, aiming to draw a connection of the interrelated intracranial ion activities. Furthermore, perspectives on the rationally designed ion level nanosensors in understanding the brain functions are highlighted.

Core-Shell-Satellite Nanomaces as Remotely Controlled Self-Fueling Fenton Reagents for Imaging-Guided Triple-Negative Breast Cancer-Specific Therapy.

Triple-negative breast cancer (TNBC) is highly aggressive and insensitive to conventional targeted therapies, resulting in poor therapeutic outcomes. Recent studies have shown that abnormal iron metabolism is observed in TNBC, suggesting an opportunity for TNBC treatment via the iron-dependent Fenton reaction. Nevertheless, the efficiency of current Fenton reagents is largely restricted by the lack of specificity and low intracellular H2 O2 level of cancer cells. Herein, core-shell-satellite nanomaces (Au @ MSN@IONP) are fabricated, as near-infrared (NIR) light-triggered self-fueling Fenton reagents for the amplified Fenton reaction inside TNBC cells. Specifically, the Au nanorod core can convert NIR light energy into heat to induce massive production of intracellular H2 O2 , thereby the surface-decorated iron oxide nanoparticles (IONP) are being fueled for robust Fenton reaction. By exploiting the vulnerability of iron efflux in TNBC cells, such a self-fueling Fenton reaction leads to highly specific anti-TNBC efficacy with minimal cytotoxicity to normal cells. The PI3K/Akt/FoxO axis, intimately involved in the redox regulation and survival of TNBC, is demonstrated to be inhibited after the treatment. Consequently, precise in vivo orthotopic TNBC ablation is achieved under the guidance of IONP-enhanced magnetic resonance imaging. The results demonstrate the proof-of-concept of NIR-light-triggered self-fueling Fenton reagents against TNBC with low ferroportin levels.

A sensitive and specific nanosensor for monitoring extracellular potassium levels in the brain.

Extracellular potassium concentration affects the membrane potential of neurons, and, thus, neuronal activity. Indeed, alterations of potassium levels can be related to neurological disorders, such as epilepsy and Alzheimer's disease, and, therefore, selectively detecting extracellular potassium would allow the monitoring of disease. However, currently available optical reporters are not capable of detecting small changes in potassium, in particular, in freely moving animals. Furthermore, they are susceptible to interference from sodium ions. Here, we report a highly sensitive and specific potassium nanosensor that can monitor potassium changes in the brain of freely moving mice undergoing epileptic seizures. An optical potassium indicator is embedded in mesoporous silica nanoparticles, which are shielded by an ultrathin layer of a potassium-permeable membrane, which prevents diffusion of other cations and allows the specific capturing of potassium ions. The shielded nanosensor enables the spatial mapping of potassium ion release in the hippocampus of freely moving mice.