T.J. Steeghs , L. van Engelshoven , S.P.L. Kuijpers , N.M.M. Coolen , C.J. van de Ridder , M. van Geffen , E.J. Lous , S.E.M. Schols , C. van’t Veer , W.L. van Heerde
{"title":"Novel microfluidic device for factor VIII quantification by chemiluminescence in hemophilia A patients","authors":"T.J. Steeghs , L. van Engelshoven , S.P.L. Kuijpers , N.M.M. Coolen , C.J. van de Ridder , M. van Geffen , E.J. Lous , S.E.M. Schols , C. van’t Veer , W.L. van Heerde","doi":"10.1016/j.bios.2025.117469","DOIUrl":"10.1016/j.bios.2025.117469","url":null,"abstract":"<div><div>Point-of-care (PoC) testing can revolutionize diagnostics, enabling early detection and disease monitoring for chronic disorders. However, current PoC systems often lack the adaptability to detect multiple analytes. We present a capillary-based microfluidic detection platform with integrated optical sensors, that allows for an array of 16 simultaneous measurements using a chemiluminescent readout. The device consists of a disposable part containing microfluidics and a reusable part with integrated optical sensors. To demonstrate proof-of-principle, the current study specifically focuses on quantifying clotting Factor VIII (FVIII), a critical parameter in Hemophilia A management. Therefore, a chemiluminescent-based FVIII assay (FVIII<sub>lum</sub>) was designed to quantify the activity levels in citrated plasma samples. All reagents necessary for the assay are contained in the disposable part of the device. To detect FIXa/FVIIIa tenase activity, a caged chemiluminescent substrate specific for activated Factor X (FXa) was synthesized for ultrasensitive real-time measurement of FVIII-mediated FXa generation. Experiments with the FVIII<sub>lum</sub>, performed with the microfluidic cartridge with dried-in reagents, showed high level of precision. In addition, the FVIII<sub>lum</sub> was capable to distinguish FVIII deficient plasma from plasma with only 0.017 IU/mL activity, demonstrating its applicability for Hemophilia A management. Finally, proof-of-principle was obtained by pharmacokinetic monitoring of FVIII activity in patient samples, demonstrating good agreement with the reference method. This study successfully presents a new miniaturized chemiluminescent platform, incorporating microfluidics and photon sensors, designed to detect multiple parameters in parallel per cartridge.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117469"},"PeriodicalIF":10.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Zhou , Gongle Shen , Linling Zhong , Genchang Chen , Liyuan Meng , Wenyin He , Jing Liu , Sen Yang , Yang Luo , Xianfeng Wang
{"title":"crRNA array-mediated CRISPR/Cas12a coupling with dual RPA for highly sensitive detection of Streptomyces aureofaciens Tü117 from hypertension with multi-signal output","authors":"Tingting Zhou , Gongle Shen , Linling Zhong , Genchang Chen , Liyuan Meng , Wenyin He , Jing Liu , Sen Yang , Yang Luo , Xianfeng Wang","doi":"10.1016/j.bios.2025.117493","DOIUrl":"10.1016/j.bios.2025.117493","url":null,"abstract":"<div><div>Accurate and sensitive detection of <em>Streptomyces aureofaciens</em> Tü117 is crucial for hypertension classification and early warning. To achieve this, a dual recombinase polymerase amplification coupled with a crRNA array-mediated CRISPR/Cas12a assay (DR-CAMCas) was developed, enabling multi-signal output for precise identification and detection of <em>S. aureofaciens</em> Tü117. The 16S rDNA and LipReg4 genes of <em>S. aureofaciens</em> Tü117 are amplified simultaneously via one-step dual RPA, activating the crRNA array-mediated CRISPR/Cas12a system to cleave exogenous FQ-reporters, releasing fluorescent signals. DR-CAMCas offers high amplification efficiency, multi-site recognition through crRNA array signal superposition, and the programmability of CRISPR/Cas12a, achieving ultrasensitive detection with a linear range of 10 to 10<sup>8</sup> cfu/mL and a limit of detection of approximately 3 cfu/mL. DR-CAMCas successfully detected <em>S. aureofaciens</em> Tü117 in fecal samples from high-salt diet-induced hypertensive mice and hypertensive patients, matching qPCR results and demonstrating high reliability and practicality. Additionally, target-induced cleavage of a DNA linker by DR-CAMCas dispersed AuNPs-DNA probes, enabling colorimetric detection. Integrated onto lateral flow sensors, DR-CAMCas allows point-of-care testing via simple visual strip analysis. Its triple signal output meets diverse detection needs, offering a promising tool for diagnosing salt-sensitive hypertension.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117493"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Zan , Li Fan , Rui Wang , Hui Wang , Yue Huang , Xue Yu , Yuewei Zhang , Chuan Dong , Shaomin Shuang
{"title":"Dual-channel fluorescent probe for simultaneously visualizing ONOO− and viscosity in epilepsy, non-alcoholic fatty liver and tumoral ferroptosis models","authors":"Qi Zan , Li Fan , Rui Wang , Hui Wang , Yue Huang , Xue Yu , Yuewei Zhang , Chuan Dong , Shaomin Shuang","doi":"10.1016/j.bios.2025.117495","DOIUrl":"10.1016/j.bios.2025.117495","url":null,"abstract":"<div><div>Intracellular peroxynitrite anion (ONOO<sup>−</sup>) and viscosity play a major part in sustaining redox homeostasis, modulating substance transport and signal transduction. Abnormalities in these factors are closely associated with multiple physiological and pathological processes. Nevertheless, due to the absence of appropriate multifunctional fluorescent sensors, concurrent identification of ONOO<sup>−</sup> and viscosity has not been achieved in many diseases, such as epilepsy and tumoral ferroptosis models. Herein, a new near-infrared (NIR) fluorescent probe (<strong>QX-DP</strong>) was rationally conceived for concurrent detection of ONOO<sup>−</sup> and viscosity. <strong>QX-DP</strong> was highly sensitive to viscosity at 668 nm and ONOO<sup>−</sup> at 752 nm which exhibited significant “turn-on” fluorescence signals, respectively. Making use of the <strong>QX-DP</strong> with dual-channel imaging capability, the ONOO<sup>−</sup> and viscosity elevated levels in brain tissue of epileptic mice were revealed for the first time, and the visualization diagnosis of non-alcoholic liver injury (NAFL) disease model was achieved. Most importantly, the concurrent utilization of viscosity and ONOO<sup>−</sup> for visualizing tumor ferroptosis has been successfully achieved not only in cancer cells and zebrafish but also in tumor mice models. Undoubtedly, in comparison with detection of a single biomarker, monitoring dual biomarkers at the same time may offer a more sensitive and dependable strategy in the diagnosis and image-assisted surgery of oxidative stress and viscosity related diseases.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117495"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinpei Pang , Zhubing Lei , Jiajian Ji , Li Fan , Xiang Mu , Hong Wang , Wen-Fei Dong , Qian Mei
{"title":"Fully integrated centrifugal microfluidic platform for rapid HLA-B∗58:01 allele identification using duplex RPA assay","authors":"Xinpei Pang , Zhubing Lei , Jiajian Ji , Li Fan , Xiang Mu , Hong Wang , Wen-Fei Dong , Qian Mei","doi":"10.1016/j.bios.2025.117479","DOIUrl":"10.1016/j.bios.2025.117479","url":null,"abstract":"<div><div>We developed a fully integrated, portable centrifugal microfluidic platform to detect HLA-B∗58:01 allele, a strong genetic risk factor for severe hypersensitivity reactions to allopurinol. This allele is located within the human leukocyte antigen (HLA) locus, which is characterized by its polymorphism and high GC content. The platform is capable of performing on chip lysis, duplex recombinase polymerase amplification (RPA) and real-time fluorescence detection of genomic DNA directly from buccal swab samples. A localized contact heating module was customized to enable fast and efficient sample lysis using a thermophilic proteinase, and a build-in internal control was incorporated to minimize diagnostic errors. All reagents are pre-stored in a disposable microfluidic chip and the swab samples can be added directly without any pre-treatment, achieving a fully automated, walk-away test. As a verification, our platform could simultaneously detect the HLA-B∗58:01 allele and the β-globin gene as an internal control, with a limit of detection (LOD) of 30 pg/μL and 3 pg/μL, respectively. Validation using buccal swabs from 12 volunteers demonstrated 100 % concordance with the gold-standard sequencing-based typing (SBT) methods. The platform demonstrated high specificity, reproducibility, and reliability. Compared to SBT, our platform significantly reduces the time-to-result (50 min vs. up to 16 h) while minimizing extensive manual labor. Its fully automated integration of sample lysis and genomic DNA analysis provides a new direction for pharmacogenetic screening, enabling personalized medicine in resource-limited settings.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117479"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrodeposited coatings for neural electrodes: A review","authors":"Linze Li , Changqing Jiang","doi":"10.1016/j.bios.2025.117492","DOIUrl":"10.1016/j.bios.2025.117492","url":null,"abstract":"<div><div>Neural electrodes play a pivotal role in ensuring safe stimulation and high-quality recording for various bioelectronics such as neuromodulation devices and brain-computer interfaces. With the miniaturization of electrodes and the increasing demand for multi-functionality, the incorporation of coating materials via electrodeposition to enhance electrodes performance emerges as a highly effective strategy. These coatings not only substantially improve the stimulation and recording performance of electrodes but also introduce additional functionalities. This review began by outlining the application scenarios and critical requirements of neural electrodes. It then delved into the deposition principles and key influencing factors. Furthermore, the advancements in the electrochemical performance and adhesion stability of these coatings were reviewed. Ultimately, the latest innovative works in the electrodeposited coating applications were highlighted, and future perspectives were summarized.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117492"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huanlong Zheng , Hao Sha , Ri Zhou , Yu Wu , Chenguang Wang , Shangguo Hou , Geyu Lu
{"title":"Rational development of Nile red derivatives with significantly improved specificity and photostability for advanced fluorescence imaging of lipid droplets","authors":"Huanlong Zheng , Hao Sha , Ri Zhou , Yu Wu , Chenguang Wang , Shangguo Hou , Geyu Lu","doi":"10.1016/j.bios.2025.117494","DOIUrl":"10.1016/j.bios.2025.117494","url":null,"abstract":"<div><div>Since the first report of Nile Red as a fluorescent probe for lipid droplets (LDs) imaging was published in 1985, this fluorescent probe has been widely used for nearly 40 years, and so far, it is still one of the most commonly used probes for LDs imaging. Although Nile Red has achieved continuous success, it has gradually emerged two major limitations (poor LDs specificity and low photostability) which directly limit the study of LDs via advanced fluorescence imaging techniques. In this context, we have developed a new synthetic route to conveniently prepare a series of Nile Red derivatives (NR-1 to NR-15). With these 15 derivatives in hand, the relationships between molecular structures and their properties (LDs specificity, photostability) have been comprehensively investigated. Consequently, we have rationally designed a new Nile Red derivative, NR-11, which exhibits significantly improved LDs specificity and photostability. Utilizing this new LDs probe, we have successfully conducted various advanced fluorescence imaging, <em>e.g.</em> time-lapse three-dimensional (3D) confocal imaging of cells, time-lapse 3D dynamic tracking of a single LD, and two-photon 3D imaging of tissues. These advanced imaging results not only demonstrate the utility of this new fluorescent probe but also provide novel insights into the cell biology study of LDs.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117494"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ding Ma , Yaojun Wang , Yi Xu , Chang Chen , Xianqiang Mi
{"title":"Cascaded logic gate-based electrochemical analysis of multiple miRNAs for cancer recognition","authors":"Ding Ma , Yaojun Wang , Yi Xu , Chang Chen , Xianqiang Mi","doi":"10.1016/j.bios.2025.117468","DOIUrl":"10.1016/j.bios.2025.117468","url":null,"abstract":"<div><div>Current miRNA detection methods mainly focus on the detection of discrete targets while overlooking the logical relationship among biomoleculars. Integrating electrochemical sensor, DNA framework probes and DNA logic gate technology for analyzing miRNAs with diverse combinations in bodily fluids provide a potential way for recognition of multiple cancers. In this work, a novel cascaded logic gate-based electrochemical (EC) analysis strategy was designed and fabricated for the discrimination of pancreatic cancer (PC), breast cancer (BC) and lung cancer (LC). Cascaded AND logic gates were constructed through the logical relationship among miR-21, miR-155, miR-373, miR-6746 and miR-1343 which abnormally expressed in PC, BC and LC. The output strands of the logic gates were captured by tetrahedral DNA framework probes modified on the electrodes of EC sensor. Three cascaded AND logic gates successfully achieved limits of detection (LOD) of 0.62 nM, 0.37 nM and 0.41 nM, and good linear relationships between current values and the concentration of miRNA combinations within the range from 1 nM to 1 μM (R<sup>2</sup> > 0.99). It was shown that multiple cascaded logic gate-based EC method could distinguish PC, BC and LC through specific miRNA combinations both in a TM buffer and in a 50 % fetal bovine serum samples. This logic gate-based EC method has the advantages of precision, high speed and logical analysis capability which provides a brand-new tool for system and precision medicine.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117468"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kemeng Zhang , Jiajun Li , Ye Li , Wen Zhang , Guohai Liang , Tao Zhang
{"title":"A self-catalytic UCNP-based nanomachine activated by duplex DNA for highly sensitive detection of CTCs","authors":"Kemeng Zhang , Jiajun Li , Ye Li , Wen Zhang , Guohai Liang , Tao Zhang","doi":"10.1016/j.bios.2025.117483","DOIUrl":"10.1016/j.bios.2025.117483","url":null,"abstract":"<div><div>Detection of circulating tumor cells (CTCs) has proven to be a crucial approach for early diagnosis, prognosis, and monitoring of cancer treatment. However, due to the low abundance of CTCs in blood, achieving accurate detection in the presence of a large number of blood cells remains challenging. In this study, we present a novel self-catalytic nanomachine for quantitative detection of CTCs, which includes a dual aptamer-triggered Catalytic Hairpin Assembly (CHA) reaction and subsequent UCNP-DNA-based biosensing. The dual-aptamer recognition, the two-step CHA reaction and the UCNP ratiometric sensing luminescence provide the assay with high specificity and sensitivity. Using MDA-MB-231 cells as model targets, the proposed detection system affords a wide linear detection range and a detection limit as low as 3 cells. Our system offers sensitive detection of CTCs without the need for enzymatic involvement, indicating its substantial potential for early cancer diagnosis and treatment based on CTCs.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117483"},"PeriodicalIF":10.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A dual-Color closed bipolar electrochemiluminescence platform for visual simultaneous diagnosis of two pluripotency markers in cancer patients’ urine","authors":"Nastaran Arab , Morteza Hosseini , Guobao Xu , Niloufar Sadeghi , Hodjattallah Rabbani","doi":"10.1016/j.bios.2025.117482","DOIUrl":"10.1016/j.bios.2025.117482","url":null,"abstract":"<div><div>Here, for the first time, we introduce a simple yet effective one-step visual approach for the concurrent detection of octamer-binding transcription factor 4 (Oct-4) and Nanog, two pivotal homeobox genes involved in regulating pluripotency in both stem cells and certain cancer cells, within human urine samples. We utilized a closed bipolar electrochemistry system to enable the electrochemiluminescence (ECL) detection of pluripotency biomarkers. This was accomplished by capturing the ECL of Ru(bpy)<sub>3</sub><sup>2+</sup> loaded into mesoporous SiO<sub>2</sub> nanoparticles and luminol incorporated into luminol@MIL-53 on the upper and lower anodic poles of BPEs in separate chambers of a bipolar cell using a digital camera. An identical electric potential was applied across the bipolar electrodes, driving the reduction of thionine acetate at the cathodic poles and thereby facilitating simultaneous light emission of the luminophores. Moreover, the incorporation of electroactive Ti<sub>3</sub>C<sub>2</sub>T<sub>x</sub> MXene-TiO<sub>2</sub> nanosheets catalyzed the electro-oxidation of co-reactants within both the Ru(bpy)<sub>3</sub><sup>2+</sup>/TPrA and luminol/H<sub>2</sub>O<sub>2</sub> systems, thereby enhancing the signal-to-background ratio and eliciting a significantly amplified visual ECL response. Under optimized conditions, the immunosensor displayed a linear response across a broad range of 100 pg mL<sup>−1</sup> to 400 ng/mL for Nanog, with a detection limit of 21.58 pg mL<sup>−1</sup>, and a linear response from 200 pg mL<sup>−1</sup> to 400 ng/mL with a detection limit of 106.24 pg mL<sup>−1</sup> for Oct-4. This study supports the immunosensor's potential for broader clinical application, where its high specificity and sensitivity could offer significant benefits in cancer diagnostics and stem cell research.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117482"},"PeriodicalIF":10.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lixia Guo , Xiaowan Li , Run Zhang , Yixuan Hou , Bolong Ma , Zheng Li , Jiye Lv , Bin Wang , Sufang Ma , Lihong Li , Lili Yan , Boye Zhang , Wen Liu , Kahleong Lim , Haipeng Diao , Shaowei Wang , Chengwu Zhang
{"title":"In situ dual-activated NIRF/PA carrier-free nanoprobe for diagnosis and treatment of Parkinson's disease","authors":"Lixia Guo , Xiaowan Li , Run Zhang , Yixuan Hou , Bolong Ma , Zheng Li , Jiye Lv , Bin Wang , Sufang Ma , Lihong Li , Lili Yan , Boye Zhang , Wen Liu , Kahleong Lim , Haipeng Diao , Shaowei Wang , Chengwu Zhang","doi":"10.1016/j.bios.2025.117473","DOIUrl":"10.1016/j.bios.2025.117473","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most common neurodegenerative disease threatening the life of millions people worldwide. Oxidative stress, mitochondrial dysfunction, and neuroinflammation are the pivotal causative elements of PD. Precise diagnosis enables timely monitoring initiation and progression of PD, thereby facilitating the formulation of customized and targeted treatment strategies. Optical imaging offers one alternative way for PD diagnosis. However, available diagnostic probes suffer from the inability to bypass the blood brain barrier (BBB). To accurately diagnose and effectively combat PD, there is an urgent need to develop an integrated diagnostic and therapeutic nanoprobe that can bypass the BBB and target the factors underlying degeneration of dopaminergic (DA) neurons. In present study, one integrated carrier-free nanoprobe HVCur-NPs towards those factors was designed and constructed. By modifying probe side chain with polypeptide, RVG29, we obtained brain-targeting HV-PEG-RVG29. It not only enables BBB penetration, but also produces near-infrared fluorescence (NIRF) and photoacoustic (PA) signals in cascade response to H<sub>2</sub>O<sub>2</sub> and viscosity. The release of loaded curcumin (CUR) prevents oxidative stress, neuroinflammation and restore mitochondrial function so as to rescue PD phenotypes. In cellular PD model, HVCur-NPs generated NIRF/PA signals in response to elevated ROS and viscosity, and ameliorated cell apoptosis by eliminating ROS and restoring mitochondria function. Moreover, in mice PD model, HVCur-NPs realized in situ NIRF/PA imaging brain, and rescued DA neuron loss and restored the behavioral deficit of PD mice, without detectable biotoxicity. This carrier-free nanoprobe opens venues for integrated diagnosis and treatment of neurodegenerative diseases.</div></div>","PeriodicalId":259,"journal":{"name":"Biosensors and Bioelectronics","volume":"282 ","pages":"Article 117473"},"PeriodicalIF":10.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}