{"title":"Alternating magnetic field-responsive engineered probiotics for anxiety therapy via gut-brain axis modulation.","authors":"Xuejun Wang, Yuhan Zhang, Yuling Chang, Yuhao Zhu, Guo Xiang, Kehua Chen, Chuanxing Feng, Zhaofang Hang, Xingang Li, Di Zhang","doi":"10.1186/s12951-025-03551-3","DOIUrl":"10.1186/s12951-025-03551-3","url":null,"abstract":"<p><p>The discovery of the gut-brain axis demonstrated bidirectional regulation between the gut and the brain. The gastrointestinal branches of the vagal nerve have been proven to directly modulate multiple functions of the central nervous system (CNS), providing great opportunities to develop novel tools to remotely regulate CNS function from the gut. Engineered bacteria, acting as oral live biotherapeutics, offer a durable and controllable way of modulating neuronal function non-invasively and with low side effects. Here, we constructed an engineered bacterium by genetically modifying Escherichia coli Nissle 1917 (EcN) with Fe<sub>3</sub>O<sub>4</sub> nanoparticles to release gamma-aminobutyric acid (GABA) under the control of the alternating magnetic fields (AMF). Bioavailability, assessed by survival rate in artificial gastric fluid, was further enhanced by encapsulating EcN with a poly-norepinephrine (NE) layer, which protected the probiotics from environmental stress and improved their viability during oral delivery. The oral administration of the EcN-GadABC@Fe-NE/AMF in restraint mice exhibited significant anxiolytic efficacy, which was attenuated by the chemogenetic counteraction of vagal sensory inhibition. Immunohistochemistry staining against c-fos showed reduced neuronal activation in both the nucleus of the solitary tract (NTS) and locus coeruleus (LC) area in the restraint mice treated by the EcN-GadABC@Fe-NE/AMF. Furthermore, acting as a probiotic, the EcN-GadABC@Fe-NE modulated gut microbiota homeostasis, additionally contributing to the alleviation of anxiety-like behaviors. This approach opens up a novel revenue for developing remote and non-invasive methods to modulate CNS function from the gut, and enhancing bacteriotherapy for mental disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"463"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540520","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":"Advanced strategy for cancer detection based on volatile organic compounds in breath.","authors":"Ziqi Jia, Yiwen Jiang, Tongxuan Shang, Heng Cao, Jiayi Li, Lin Cong, Pengming Pu, Hengyi Xu, Yuchen Liu, Yansong Huang, Dongxu Ma, Jiang Wu, Ruijie Zhou, Xiang Wang, Chang Bao Han, Jiaqi Liu","doi":"10.1186/s12951-025-03526-4","DOIUrl":"10.1186/s12951-025-03526-4","url":null,"abstract":"<p><p>The analysis of volatile organic compounds (VOCs) in exhaled breath has emerged as a promising non-invasive approach for cancer diagnosis, offering advantages in speed, safety, cost-effectiveness, and real-time monitoring. Two primary methodologies are employed for VOCs detection: mass spectrometry (MS)-based techniques, which provide high-precision identification and quantification of individual compounds, and sensor-based pattern recognition methods, which detect disease-specific VOC signatures. Despite their diagnostic potential, inconsistencies in accuracy highlight the need for a comprehensive evaluation of these techniques. This review synthesizes evidence from clinical studies through meta-analysis to assess the diagnostic performance of MS and sensor-based approaches. Furthermore, we examine variations in VOC profiles across cancer types, which may influence diagnostic precision, and discuss key biomarkers, analytical methodologies, current challenges, and future directions in VOCs-based diagnostics. Meta-analysis revealed a high diagnostic accuracy, with a mean area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI 0.91-0.96), sensitivity of 89% (95% CI 87%-90%), and specificity of 87% (95% CI 84%-88%). Notably, no significant difference was observed between MS and sensor-based methods (AUC: 0.91 vs. 0.93, p = 0.286), supporting the potential of sensor technologies for clinical application. Subgroup analysis further indicated no statistical difference in AUCs between heterogeneous and homogeneous sensor groups, suggesting that simplified detection systems may be feasible. Despite these promising results, standardization of protocols and methodological consistency remain critical challenges. Future efforts should focus on large-scale, well-designed clinical trials to validate and optimize VOCs-based breath tests, enhancing their diagnostic reliability and translational potential in oncology.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"468"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540546","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}
Tinglin Zhang, Yating Zheng, Tielou Chen, Yuankai Gu, Yingli Gong, Dewei Wang, Zhaoshen Li, Yiqi Du, Li Zhang, Jie Gao
{"title":"Biomaterials mediated 3R (remove-remodel-repair) strategy: holistic management of Helicobacter pylori infection.","authors":"Tinglin Zhang, Yating Zheng, Tielou Chen, Yuankai Gu, Yingli Gong, Dewei Wang, Zhaoshen Li, Yiqi Du, Li Zhang, Jie Gao","doi":"10.1186/s12951-025-03455-2","DOIUrl":"10.1186/s12951-025-03455-2","url":null,"abstract":"<p><p>Helicobacter pylori (HP) is a major etiological agent of gastric cancer, with a global prevalence of around 50%. Current treatments, primarily based on antibiotics, face challenges such as increasing drug resistance and disruption of the gut microbiota. This review proposes a holistic integrative medicine (HIM) approach, guided by the 3R concept (Remove, Remodel, and Repair), to address these limitations. The 3R concept offers a novel paradigm for the integrated prevention and treatment of HP infections: Remove targets the direct eradication of HP by overcoming antibiotic resistance, Remodel focuses on reshaping the immune microenvironment to clear pathogens, and Repair emphasizes the restoration of the gastric mucosa and protection of the gut microbiota. We discuss the potential of biomaterials, including nanoparticles for targeted drug delivery and ROS generation, hydrogels for sustained release and mucosal repair, microspheres for enhanced drug loading and controlled release, and probiotics for microbiota restoration. Additionally, multimodal therapies such as phototherapy, sonodynamic therapy, and magnetic hyperthermia provide non-invasive, targeted treatments. These innovations align with HIM principles, integrating pathogen eradication with mucosal healing and microbiome protection. Future research should focus on optimizing these materials and validating their clinical applicability to improve patient outcomes and combat antibiotic resistance.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"475"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540521","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}
Anh Duy Do, Shing-Shung Chu, Le Hien Giang, Pei-Lin Huang, Yu-Ling Lin, Che-Chang Chang, Tai-Tong Wong, Shian-Ying Sung, Chia-Ling Hsieh
{"title":"Delivery of LOXL1-AS1-siRNAs using targeting peptide-engineered extracellular vesicles with focused ultrasound to suppress medulloblastoma metastasis.","authors":"Anh Duy Do, Shing-Shung Chu, Le Hien Giang, Pei-Lin Huang, Yu-Ling Lin, Che-Chang Chang, Tai-Tong Wong, Shian-Ying Sung, Chia-Ling Hsieh","doi":"10.1186/s12951-025-03554-0","DOIUrl":"10.1186/s12951-025-03554-0","url":null,"abstract":"<p><strong>Background: </strong>Metastasis of medulloblastomas (MBs) is difficult to treat and remains the primary cause of death in children with this brain tumor. Current treatment focuses on radiotherapy to limit metastatic recurrence and maintain survival, but this may cause long-term neurocognitive deficits. This challenge emphasizes the need for novel targeted therapies to combat metastatic MB. In this study, we report an RNA therapy model using targeted extracellular vesicles (EVs) to deliver therapeutic small-interfering (si)RNAs to MB.</p><p><strong>Results: </strong>First, MB-targeted EVs (MB-tEVs) were generated via genetic modification of EV-producing cells to express E1-3, an MB-specific peptide. Next, isolated MB-tEVs were loaded with siRNAs that targeted LOXL1-AS1, a pro-metastatic long non-coding RNA in sonic-hedgehog MB (SHH-MB). Expression of the E1-3 peptide increased MB-tEV internalization into MB cells, where the delivered siRNAs effectively silenced LOXL1-AS1 and suppressed LOXL1-AS1-mediated metastatic traits of SHH-MB cells in vitro. Locoregional application of microbubble-enhanced focused ultrasound (FUS) improved the accumulation of systemically injected EVs in the mouse brain. Mice treated with siRNA-loaded MB-tEVs had decreased LOXL1-AS1 expression, reduced metastases, and improved survival in an SHH-MB orthotopic model.</p><p><strong>Conclusions: </strong>Our study provides the first and very promising evidence for the combined use of tumor-targeted EVs and microbubble-enhanced FUS to deliver therapeutic siRNAs to suppress metastatic MB, potentially supporting conventional treatments and improving clinical outcomes of this malignant pediatric tumor.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"460"},"PeriodicalIF":10.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475626","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":"Advancing liver cancer treatment with dual-targeting CAR-T therapy.","authors":"Ze Yang, Chao Cheng, Zhongliang Li, Huajing Wang, Mengmei Zhang, Ermin Xie, Xu He, Bing Liu, Hongwei Sun, Jiantao Wang, Xiaopei Li, Dingjie Liu, Xiaowen Lin, Xianyang Li, Ping Jiang, Ligong Lu, Xiaowen He, Meixiao Zhan, Ke He, Wei Zhao","doi":"10.1186/s12951-025-03512-w","DOIUrl":"10.1186/s12951-025-03512-w","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy targeting glypican-3 (GPC3) has shown promise in the treatment of hepatocellular carcinoma (HCC). However, the efficacy of CAR-T cells that focus solely on cell surface tumor-associated antigens is often limited. To overcome this challenge, we developed a dual-targeting CAR-T cell strategy. The intracellular alpha-fetoprotein (AFP) antigen, a well-established biomarker of liver cancer, presents the immunogenic Human Leukocyte Antigen (HLA)-A*02:01-restricted epitope 158-166. Consequently, we engineered a T cell receptor (TCR) mimic antibody with high specificity and affinity, providing a promising therapeutic avenue to target this critical antigen. To enhance treatment outcomes for liver cancer, we further modified previously developed GPC3 CAR-T cells, which demonstrated robust anti-tumor efficacy against GPC3-high tumor cells, to secrete an optimized bispecific T cell engager (BiTE) targeting the presented AFP antigen. This dual-targeting strategy significantly improved CAR-T cell proliferation and persistence, as well as enhancing cytokine expression and anti-tumor activity against HCC cells, particularly those exhibiting low GPC3 and AFP expression, both in vitro and in vivo. Our findings highlight the potential of this innovative approach to offer more effective treatment options for patients with liver cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"462"},"PeriodicalIF":10.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475615","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}
Qiaoqi Chen, Huilin Yu, Lin Li, Hua Zhang, Mixiao Tan, Weiwei Liu, Min Zheng, Yaqin Hu, Long Cheng, Yushi Chen, Haitao Ran, Qiu Zeng, Yuan Guo
{"title":"An imaging-guided self-amplifying photo-immunotherapeutic nanoparticle for STING pathway activation and enhanced cancer therapy.","authors":"Qiaoqi Chen, Huilin Yu, Lin Li, Hua Zhang, Mixiao Tan, Weiwei Liu, Min Zheng, Yaqin Hu, Long Cheng, Yushi Chen, Haitao Ran, Qiu Zeng, Yuan Guo","doi":"10.1186/s12951-025-03536-2","DOIUrl":"10.1186/s12951-025-03536-2","url":null,"abstract":"<p><p>The stimulator of interferon genes (STING) pathway is a promising target in cancer immunotherapy. However, current nanomedicine strategies targeting the STING pathway often suffer from limited tumor specificity and insufficient immune activation. In this study, we developed a novel imaging-guided, self-amplifying photo-immunotherapeutic nanoparticle (SSCOL), comprising a liposome framework that encapsulates the phase-change material perfluoropentane (PFP), the photothermal agent superparamagnetic iron oxide (SPIO), and the STING agonist cGAMP. This nanoparticle exhibits excellent photoacoustic/ultrasound dual-modal imaging capability, enabling precise visualization of tumor tissue. CREKA enables specific binding to fibrin-fibronectin complexes in the tumor stroma, while NIR-induced photothermal effects of SPIO trigger coagulation, amplifying target formation and enhancing nanoparticle accumulation via a positive feedback mechanism. Under photothermal therapy, the phase transition of SSCOL enables the controlled and efficient release of the encapsulated cGAMP, which subsequently activates the STING pathway and triggers a pro-inflammatory cascade, enhances dendritic cell maturation and cytotoxic T lymphocyte activation, and elicits robust immune responses against both primary and metastatic tumors. Collectively, this multifunctional nanoparticle offers a promising strategy that integrates imaging, targeting, and photothermal-enhanced immune activation for STING-mediated cancer immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"459"},"PeriodicalIF":10.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340205","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}
Chenchen Tang, Xinyi Tang, Jingwei Tang, Jie Hu, Li Wan, Jimei Chen, Ruqian Fu, Yang Cao, Rui Li
{"title":"An oxygen-generating nanoplatform remodels the immunosuppressive tumor microenvironment via synergistic lactate depletion and sonodynamic therapy.","authors":"Chenchen Tang, Xinyi Tang, Jingwei Tang, Jie Hu, Li Wan, Jimei Chen, Ruqian Fu, Yang Cao, Rui Li","doi":"10.1186/s12951-025-03524-6","DOIUrl":"10.1186/s12951-025-03524-6","url":null,"abstract":"<p><p>Lactate is an immunosuppressive molecule that plays an important role in tumor progression. Regulating lactate metabolism to remodel the immunosuppressive microenvironment represents a promising strategy for cancer therapy. However, owing to the hypoxic nature of the tumor microenvironment and single intervention strategies, the effect of lactate oxidase for cancer therapy is not as expected. Therefore, we engineered a self-oxygen-generating nanoplatform by encapsulating lactate oxidase and manganese porphyrin within nanoliposomes (ML@Lip). Lactate depletion via lactate oxidase promoted the polarization of tumor-associated macrophages toward the M1 phenotype in the tumor microenvironment and modulated innate antitumor immunity. Manganese porphyrin-mediated sonodynamic therapy induced not only tumor cell apoptosis but also immunogenic cell death. The release of damage-associated molecular patterns promoted dendritic cell maturation and T-cell activation, leading to immune system activation and the initiation of adaptive immunity. Additionally, manganese catalyzed the decomposition of hydrogen peroxide (derived from lactate breakdown) to generate substantial oxygen. This process established a positive feedback loop via lactate depletion while amplifying sonodynamic therapeutic effects through enhanced oxygen production. Therefore, the strategy of combining lactate depletion-induced starvation therapy, sonodynamic therapy and self-circulating oxygen generation effectively remodeled the immunosuppressive tumor microenvironment and inhibited tumor growth, thereby providing novel insights into targeted lactate metabolism therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"458"},"PeriodicalIF":10.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336694","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}