Yong Fu, Jiahui Hou, Qinmeng Yang, Yanpeng Lin, Nie Rui, Jun Wang, Hangtian Wu, Bin Yu
{"title":"Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis.","authors":"Yong Fu, Jiahui Hou, Qinmeng Yang, Yanpeng Lin, Nie Rui, Jun Wang, Hangtian Wu, Bin Yu","doi":"10.1186/s12951-025-03543-3","DOIUrl":"10.1186/s12951-025-03543-3","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA), the most prevalent joint disorder, is characterized by a complex etiology and a lack of safe and effective therapeutic interventions. Emerging evidence suggests that immune cell dysregulation plays a pivotal role in the pathogenesis of OA. Recent advancements in high-throughput sequencing technologies, along with the integration of machine learning into medical research, have provided novel insights into the molecular mechanisms underlying various diseases. However, the specific roles and mechanisms of immune-related factors in OA remain poorly understood. This study aims to identify potential biomarkers for the diagnosis and monitoring of OA progression and to explore targeted therapeutic strategies based on key genes associated with the disease.</p><p><strong>Results: </strong>WGCNA and immune infiltration analysis identified SIK1 as a core gene involved in immune regulation during the progression of OA. In vitro experiments demonstrated that AICAR, an activator of SIK1, significantly suppressed inflammatory responses by modulating glucose and lipid metabolism in macrophages. A novel nanoliposome composite hydrogel, Gel@Lipo@AICAR, has been successfully developed for the targeted delivery of AICAR. The intra-articular administration of Gel@Lipo@AICAR demonstrated excellent biosafety and therapeutic potential in mitigating the progression of OA.</p><p><strong>Conclusions: </strong>This study identifies SIK1 as a novel biomarker for diagnosing and monitoring the progression of OA. The anti-inflammatory effects of its agonist, AICAR, were validated, underscoring its role in reprogramming macrophage glucose and lipid metabolism. Furthermore, the development of Gel@Lipo@AICAR, a nanoliposome composite hydrogel, presents a promising therapeutic strategy for the treatment of OA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"486"},"PeriodicalIF":10.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhang Zhang, Luhao Guan, Yue Zhang, Juan Yao, Shuo Gu
{"title":"LUPP-LAMP: one-pot multiplatform universal LAMP assay for simultaneous detection and genotyping of DENV and ZIKV.","authors":"Zhang Zhang, Luhao Guan, Yue Zhang, Juan Yao, Shuo Gu","doi":"10.1186/s12951-025-03581-x","DOIUrl":"10.1186/s12951-025-03581-x","url":null,"abstract":"<p><p>Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne viruses that cause severe health problems upon infection, necessitating timely and accurate diagnostic testing for effective prevention and control of their transmission. In this study, a novel multiplex nucleic acids detection method was introduced based on ligation-based universal primer and probe loop-mediated isothermal amplification (LUPP-LAMP) for the simultaneous detection and genotyping of DENV and ZIKV. By employing ligation of universal primers and probes using splint DNA ligase, LUPP-LAMP simplifies primer design, eliminates primer dimer formation, and achieves high sensitivity and specificity at low temperatures, with a detection limit of 10 copies/reaction. The robustness of this strategy allows for precise differentiation even at low concentrations and in cases of co-infection, which is crucial for addressing early diagnostic challenges due to similar symptoms. LUPP-LAMP is further adapted for point-of-care testing (POCT) by integrating lateral flow test strips and fluorescence imaging, offering rapid and user-friendly results in resource-limited settings. This method is also applied to DENV genotyping (serotypes 1-4) using melting curve analysis (MCA) in cases of co-infection, aiding in epidemiological surveillance and intervention strategies. In summary, LUPP-LAMP represents a significant advancement in the detection and genotyping of DENV and ZIKV, offering a versatile tool for laboratory and POCT applications, thereby enhancing public health outcomes in the control of mosquito-borne diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"490"},"PeriodicalIF":10.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Shi, Peng Zhou, Cong Ye, Jie Sun, Hongdong Ma, Ran Tao, Peng Zhang, Fei Han
{"title":"Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon-bone healing.","authors":"Lei Shi, Peng Zhou, Cong Ye, Jie Sun, Hongdong Ma, Ran Tao, Peng Zhang, Fei Han","doi":"10.1186/s12951-025-03580-y","DOIUrl":"10.1186/s12951-025-03580-y","url":null,"abstract":"<p><p>Enhanced tendon‒bone healing is of critically importance for achieving optimal postoperative recovery following a rotator cuff tendon tear (rotator cuff tears, RCTs). Although RCTs patch-augmented scaffolds demonstrate clinical potential, there is a paucity of reports on biodegradable scaffolds that effectively integrate high strength and bioactivity. Inspired by the composition and aligned nanofibrous structure of the natural fish bladder matrix (fish swim bladder, FSB), we employed a gallium (Ga)‒tannic acid (TA) metal‒polyphenol network (MPN)-modified decellularized fish bladder matrix (GaPP@FSB) as a novel biomaterial to address this problem. Ga-TA MPN represents a \"two birds with one stone\" modification strategy that allows GaPP@FSB to demonstrate commendable mechanical strength alongside multiple biological activities, including antibacterial, antioxidant, anti-inflammatory and osteogenic differentiation promotion. Furthermore, GaPP@FSB regulates the focal adhesion-based mechanical signal transduction pathway in tendon stem/progenitor cells (TSPCs), thereby activating the α5β1/Akt/PI3K pathway to induce tenogenic differentiation. Additionally, this scaffold exhibits remarkable anti-inflammatory and antibacterial activities. In a rat RCTs model, GaPP@FSB promoted regeneration at the tendon‒bone interface while restoring both rotator cuff biomechanics and joint movement function. Consequently, this biomaterial derived from natural FSB has outstanding biosafety and biological activity, making it a highly promising candidate for clinical applications in both tendon repair and the restoration of the tendon‒bone interface.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"489"},"PeriodicalIF":10.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Zhang, Xiuluan Du, Xin Dai, Yanxiang Liu, Kai Guo, Donghua Gu
{"title":"SIRT5-modified human umbilical cord mesenchymal stem cells loaded with antioxidant polydopamine nanozyme enhance parpi resistance in ovarian cancer via fatty acid metabolism reprogramming.","authors":"Jin Zhang, Xiuluan Du, Xin Dai, Yanxiang Liu, Kai Guo, Donghua Gu","doi":"10.1186/s12951-025-03516-6","DOIUrl":"10.1186/s12951-025-03516-6","url":null,"abstract":"<p><p>Ovarian cancer remains one of the most aggressive cancers, and resistance to Poly (ADP-ribose) Polymerase inhibitors (PARPi) poses a major therapeutic challenge. SIRT5, a NAD + -dependent desuccinylase, plays a crucial role in regulating fatty acid metabolism, which is often reprogrammed in cancer cells to promote drug resistance. This study aimed to investigate the potential of polydopamine (PDA)-polymerized antioxidant nanozyme-loaded SIRT5-modified human umbilical cord mesenchymal stem cells (hUCMSCs) to overcome PARPi resistance in ovarian cancer. We employed multi-omics approaches, including transcriptomics, metabolomics, and proteomics, to identify key molecular pathways associated with resistance mechanisms. High-throughput sequencing and metabolic profiling revealed that SIRT5 modifies fatty acid β-oxidation and regulates the desuccinylation of Enoyl-CoA Hydratase (ECHA), a key enzyme involved in this process. In vitro and in vivo experiments demonstrated that nanozyme-engineered hUCMSCs effectively enhanced PARPi resistance by promoting fatty acid metabolism and desuccinylation. These findings suggest that SIRT5-modified hUCMSCs loaded with antioxidant nanozymes offer a promising therapeutic strategy to combat PARPi resistance in ovarian cancer. The study provides new insights into overcoming drug resistance through metabolic reprogramming and enhances the potential of engineered stem cells in cancer therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"485"},"PeriodicalIF":10.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chaofeng Liang, Rong Li, Zeyu Pu, Ran Chen, Yuzhuang Li, Siqi Chen, Jinzhu Feng, Jie Liu, Yuteng Bai, Xuewen Qin, Chengjie Xie, Yixin Zhang, Yi Peng, Hui Tang, Mei Zhang, Qiuyue Zhang, Tao Wang, Baisheng Li, Huan Zhang, Xu Zhang, Yun He, Xin He, Ting Pan, Hui Zhang, Yiwen Zhang
{"title":"Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants.","authors":"Chaofeng Liang, Rong Li, Zeyu Pu, Ran Chen, Yuzhuang Li, Siqi Chen, Jinzhu Feng, Jie Liu, Yuteng Bai, Xuewen Qin, Chengjie Xie, Yixin Zhang, Yi Peng, Hui Tang, Mei Zhang, Qiuyue Zhang, Tao Wang, Baisheng Li, Huan Zhang, Xu Zhang, Yun He, Xin He, Ting Pan, Hui Zhang, Yiwen Zhang","doi":"10.1186/s12951-025-03582-w","DOIUrl":"10.1186/s12951-025-03582-w","url":null,"abstract":"<p><p>The emergence of SARS-CoV-2 variants has underscored the urgent need for innovative vaccine strategies that provide robust and enduring protection against diverse strains. Our study introduces the FP-HR5 nanoparticle vaccine, designed to target the highly conserved S2 subunit of the spike protein, including the fusion peptide (FP) and heptad repeats (HR1 and HR2), using a 24-mer Helicobacter pylori ferritin platform. Administered intranasally, the FP-HR5-NP vaccine elicits robust systemic and mucosal immune responses in vivo, generating high titers of FP- and HR5-specific IgG antibodies. Notably, intranasal immunization resulted in elevated levels of secretory IgA and IgG in bronchoalveolar lavage fluid (BALF) and stimulated T-cell immune responses, significantly increasing resident memory B cells (B<sub>RM</sub>) and resident memory T cells (T<sub>RM</sub>) in the lungs. In hACE2 transgenic mice, three doses of FP-HR5-NP conferred substantial protection against Delta and Omicron variant challenges, with undetectable viral RNA levels in the lungs and no pathological changes observed. Overall, the FP-HR5-NP vaccine triggers comprehensive humoral and cellular immune responses at the mucosa, providing broad defense against SARS-CoV-2 variants and positioning it as a promising candidate for a universal COVID-19 vaccine solution.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"483"},"PeriodicalIF":10.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LNP-enclosed NamiRNA inhibits pancreatic cancer proliferation and migration via dual pathways.","authors":"Chao Yu, Zhou Fang, Qingyu Xie, Zhuo Wu, Peixian Huang, Jinlong Yu, Rufu Chen","doi":"10.1186/s12951-025-03550-4","DOIUrl":"10.1186/s12951-025-03550-4","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a highly aggressive malignancy characterized by limited treatment options, poor prognosis, and high mortality rates. nuclear activating miRNA (NamiRNA) enhances gene expression by interacting with nuclear enhancers, offering a novel avenue for understanding gene regulation in cancer. This study explores the dual role of mir-200c in regulating tumor proliferation and migration in pancreatic cancer, with the aim of identifying potential therapeutic strategies.</p><p><strong>Results: </strong>Mir-200c significantly activated PTPN6 transcription via the NamiRNA-enhancer pathway, reducing tumor proliferation. Deletion of the enhancer sequence abolished the activation of PTPN6. Furthermore, mir-200c mediated the post-transcriptional repression of CDH17, impairing tumor migration. In vivo, LNP-enclosed mir-200c exhibited strong anti-tumor effects, further validating its therapeutic potential.</p><p><strong>Conclusions: </strong>Mir-200c inhibits pancreatic cancer cell proliferation and migration through dual mechanisms: activation of PTPN6 transcription and repression of CDH17 expression. These findings suggest that mir-200c, particularly when delivered via LNP systems, may serve as a promising therapeutic strategy for pancreatic cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"484"},"PeriodicalIF":10.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dingding Liu, Chenyu Zhang, Yuanyuan Ye, Piao Mei, Yang Gong, Zhen Liu, Chao Sun, Xuecheng Zhao, Shiqi Ding, Jiedan Chen, Liang Chen, Chunlei Ma
{"title":"TEA5K: a high-resolution and liquid-phase multiple-SNP array for molecular breeding in tea plant.","authors":"Dingding Liu, Chenyu Zhang, Yuanyuan Ye, Piao Mei, Yang Gong, Zhen Liu, Chao Sun, Xuecheng Zhao, Shiqi Ding, Jiedan Chen, Liang Chen, Chunlei Ma","doi":"10.1186/s12951-025-03533-5","DOIUrl":"10.1186/s12951-025-03533-5","url":null,"abstract":"<p><strong>Background: </strong>High-throughput genotyping technology has become an indispensable tool for advancing molecular breeding and genetic research in plants, facilitating large-scale exploration of genomic variation. Genotyping technology based on liquid-phase array utilizes streptavidin-coated nanomagnetic beads to capture biotin-modified probes, thereby capturing the target sequence on the genome, achieving the purpose of genotyping. This study aims to develop a novel liquid-phase for tea plant, which can be used for cultivar identification, genetic map construction, Quantitative Trait Locus (QTL) mapping of key agronomic traits in tea plants, and genetic evolution analysis.</p><p><strong>Result: </strong>We developed a highly efficient multiple-SNP array, the TEA5K mSNP array, which comprises 5,781 liquid-phase probes based on the Genotyping by Target Sequencing (GBTS) system. Using this array, we genotyped 231 developed tea cultivars, revealing that genetic similarity within the same cultivar ranged from 92.53-97.95%, whereas genetic similarity between different cultivars generally remained below 82.36%. Furthermore, utilizing this array, we constructed a high-density genetic map consisting of 3,274 markers, covering a total genetic distance of 2,225.19 cM, with an average marker interval of 0.76 cM. The high-resolution genetic map facilitated the identification of multiple QTLs linked to eight amino acid components, as well as two molecular markers strongly associated with the albino-leaf trait in the 'Huangjinya' cultivar, both mapped to chromosome 8. Moreover, we applied the array to analyze the population structure and phylogenetic relationships of 519 tea germplasm, classifying them into three major groups: wild accessions, landraces, and modern cultivars. Notably, modern cultivars exhibited lower genetic diversity compared to landraces. Additionally, we observed substantial genetic differentiation between wild resources and modern cultivars, with minimal to no gene flow from wild populations into domesticated cultivars. These findings suggest that modern tea breeding faces an \"improvement bottleneck,\" a challenge similar to that encountered in other perennial crops.</p><p><strong>Conclusion: </strong>The TEA5K mSNP array is presented as a flexible, cost-effective, and low-maintenance genotyping tool that significantly enhances both genetic research and molecular breeding in tea plants. By providing a robust platform for genome-wide analysis and facilitating the identification of key QTLs, this tool offers valuable insights for improving the genetic diversity and agronomic performance of tea cultivars.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"481"},"PeriodicalIF":10.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrasmall nanoparticles for co-delivery of antisense oligonucleotides targeting miR-21 and miR-210 to treat glioblastoma.","authors":"Ravi Raj Singh, Ritu Kulshreshtha, Amirali Popat","doi":"10.1186/s12951-025-03529-1","DOIUrl":"10.1186/s12951-025-03529-1","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common and aggressive type of brain tumour, with less than 5% of patients surviving more than 5 years. Despite decades of research to understand the underlying pathophysiological causes, it has witnessed very slow progress in terms of clinical translation of therapies. This is partially due to the lack of effective delivery strategies for overcoming major obstacles such as blood-brain barrier (BBB) and blood tumour barrier (BTB). Out of the pool of the oncogenic microRNAs, miR-21 and miR-210 are known to regulate several hallmarks of GBM tumorigenesis. Targeting these dysregulated microRNAs using antisense oligonucleotides has a huge therapeutic potential for GBM therapy. However, such microRNAs cannot be delivered without an effective delivery system, which is one of the biggest hurdles in developing RNA-based therapeutics for GBM. Herein, we have developed ultra-small mesoporous silica nanoparticles (USMP) of ~ 40 nm size and modified with Polyethyleneimine (PEI) in a w/w ratio ranging from 1:1 to 1:0.01 (USMP-PEI). We have successfully demonstrated that by optimizing the PEI ratio with close to neutral surface charge, we were able to reduce PEI-induced cytotoxicity without compromising the transfection efficiency. Using the optimized USMP-PEI (1:0.025) w/w ratio and using it to further complex with different (w/w) ratios with antisense oligonucleotides (miR-21 and miR-210), we report a slow and sustained release of antisense oligonucleotides at pH 7.4. With the current strategy, we report significant cellular uptake of microRNAs in the 2D cellular model (LN229 cells) 1 h post-transfection as well as significant penetration of oligonucleotides deep within the hypoxic core of 3D GBM spheroids. The modified USMP complexed with antisense oligonucleotides possesses the inherent ability to transiently penetrate the BBB validated by transwell assay. Simultaneously, they were also able to significantly reduce the tumor spheroid size generated by LN229 GBM cells by around 30% and colony count by around 40% when anti-miRs were delivered in combination for effective GBM therapy. Taken together, these promising data will pave the way for further pre-clinical assessment of this newly developed nanomedicine for the delivery of microRNAs across the brain.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"482"},"PeriodicalIF":10.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqi Gao, Bayinqiaoge Bayinqiaoge, Ming Li, Rona Chandrawati, Xiangpeng Li, Lining Sun, Chun H Wang, Chengchen Zhang, Shi-Yang Tang
{"title":"Stimuli-responsive smart materials enabled high-performance biosensors for liquid biopsies.","authors":"Xiaoqi Gao, Bayinqiaoge Bayinqiaoge, Ming Li, Rona Chandrawati, Xiangpeng Li, Lining Sun, Chun H Wang, Chengchen Zhang, Shi-Yang Tang","doi":"10.1186/s12951-025-03541-5","DOIUrl":"10.1186/s12951-025-03541-5","url":null,"abstract":"<p><p>Liquid biopsies have emerged as a key tool that enables personalized medicine, enabling precise detection of biochemical parameters to tailor treatments to individual needs. Modern biosensors enable real-time detection, precise diagnosis, and dynamic monitoring by rapidly analyzing biomarkers such as nucleic acids, proteins, and metabolites in bodily fluids like blood, saliva, and urine. Despite their potential, many biosensors are still constrained by mono-functionality, sub-optimal sensitivity, bulky designs, and complex operation requirements. Recent advances in stimuli-responsive smart materials present a promising pathway to overcome these limitations. These materials enhance biomarker signal transduction, release, or amplification, leading to improved sensitivity, simplified workflows, and multi-target detection capabilities. Further exploration of the integration of these smart materials into biosensing is therefore essential. To this end, this review critically examines and compares recent progress in the development and application of physical, chemical, and biochemical stimuli-responsive smart materials in biosensing. Emphasis is placed on their responsiveness mechanisms, operational principles, and their role in advancing biosensor performance for biomarker detection in bodily fluids. Additionally, future perspectives and challenges in developing versatile, accurate, and user-friendly biosensors for point-of-care and clinical applications using these smart materials are discussed.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"477"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}