Journal of Nanobiotechnology最新文献

{"title":"A novel pan-epitope based nanovaccine self-assembled with CpG enhances immune responses against flavivirus.","authors":"Jiuxiang He, Xiaoyan Ding, Jing Zhao, Jie Zeng, Yuxin Zhou, Wen Xiao, Dong Hua, Minchi Liu, Hongxia Guo, Yu Zhang, Minyue Qiu, Jintao Li","doi":"10.1186/s12951-024-03031-0","DOIUrl":"10.1186/s12951-024-03031-0","url":null,"abstract":"<p><strong>Background: </strong>Flavivirus is a highly prevalent and outbreak-prone disease, affecting billions of individuals annually and posing substantial public health challenges. Vaccination is critical to reducing the global impact of flavivirus infections, making the development of a safe and effective vaccine a top priority. The self-assembled pan-epitope vaccine presents key advantages for improving immunogenicity and safety without relying on external vectors or adding immunomodulatory elements, both of which are essential for successful vaccine development.</p><p><strong>Results: </strong>In this study, the pan-epitope peptide TBT was combined with adjuvant CpG to form the TBT-CpG nanovaccine (TBT-CpG NaVs), which was found to be spherical, uniform in shape, and demonstrated strong serum stability. In vitro studies showed that the TBT-CpG NaVs were efficiently taken up and internalized by bone marrow-derived dendritic cells (BMDCs). Flow cytometry and transcriptomic analysis indicated that the antigens were effectively presented to antigen-presenting cells (APCs) via the MHC II pathway, which facilitated BMDCs maturation and promoted the release of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. In vivo studies confirmed that TBT-CpG NaVs enhanced antigen-specific IgG levels, significantly increased IFN-γ and IL-4 expression in spleen cells, and offered protective effects against Dengue virus (DENV) and Zika virus (ZIKV) infections. Safety evaluations revealed no hepatotoxicity and no significant organ damage in immunized mice.</p><p><strong>Conclusion: </strong>The self-assembled candidate nanovaccine TBT-CpG NaVs effectively activates BMDCs and triggers a targeted immune response, providing antiviral effects against DENV and ZIKV. This vaccine demonstrates good immunogenicity and safety, establishing a promising foundation and a new strategy for the development of safe and effective vaccines.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"738"},"PeriodicalIF":10.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750039","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":"From dansyl-modified biofilm disruptors to β-cyclodextrin-optimized multifunctional supramolecular nanovesicles: their improved treatment for plant bacterial diseases.","authors":"Hui-Ling Zhang, Hong-Wei Wang, Jing-Han Yang, Jia-Jia Chen, Juan Liu, Qing-Chuan Shi, Hai-Cong Zhao, Mo-Xian Chen, Run Yang, Qing-Tian Ji, Pei-Yi Wang","doi":"10.1186/s12951-024-03028-9","DOIUrl":"10.1186/s12951-024-03028-9","url":null,"abstract":"<p><strong>Background: </strong>Bacterial diseases caused by phytopathogenic Xanthomonas pose a significant threat to global agricultural production, causing substantial economic losses. Biofilm formation by these bacteria enhances their resistance to environmental stressors and chemical treatments, complicating disease control. The key to overcoming this challenge lies in the development of multifunctional green bactericides capable of effectively breaking down biofilm barriers, improving foliar deposition properties, and achieving the control of bacterial diseases.</p><p><strong>Results: </strong>We have developed a kind of innovative green bactericide from small-molecule conception to eco-friendly supramolecular nanovesicles (DaPA8@β -CD) by host-guest supramolecular technology. These nanoscale assemblies demonstrated the ability to inhibit and eradicate biofilm formation, while also promoted foliar wetting and effective deposition properties, laying the foundation for improving agrochemical utilization. Studies revealed that DaPA8@β -CD exhibited significant biofilm inhibition (78.66% at 7.0 µ g mL^- 1) and eradication (83.50% at 25.0 µ g mL^- 1), outperforming DaPA8 alone (inhibition: 59.71%, eradication: 66.79%). These nanovesicles also reduced exopolysaccharide formation and bacterial virulence. In vivo experiments showed enhanced control efficiency against citrus bacterial canker (protective: 78.04%, curative: 50.80%) at a low dose of 200 µ g mL^- 1, superior to thiodiazole-copper-20%SC and DaPA8 itself.</p><p><strong>Conclusion: </strong>This study demonstrates the potential of DaPA8@β -CD nanovesicles as multifunctional bactericides for managing Xanthomonas -induced plant diseases, highlighting the advantages of using host-guest supramolecular technology to enhance agrochemical bioavailability.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"739"},"PeriodicalIF":10.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750393","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":"Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway.","authors":"Yafei Tian, Dandan Sun, Na Liu, Jianan Zhao, Tongjian Zhao, Xiaonan Liu, Xinzhe Dong, Li Dong, Wei Wang, Ping Jiao, Jie Ma","doi":"10.1186/s12951-024-03029-8","DOIUrl":"10.1186/s12951-024-03029-8","url":null,"abstract":"<p><p>Hepatic fibrosis is a common disease with high morbidity and mortality rates. The complex and poorly understood mechanisms underlying hepatic fibrosis represent a significant challenge for the development of more effective therapeutic strategies. MKP5 is a potential regulator of multiple fibrotic diseases. However, its precise role and mechanism of action in hepatic fibrosis remains unclear. This study identified a reduction in MKP5 expression in fibrotic liver tissues of mice treated with CCl₄ and observed that MKP5 knockout mice exhibited a more pronounced development of hepatic fibrosis. In addition, RNA-seq data indicated activation of protein processing in the endoplasmic reticulum signalling pathway in fibrotic liver tissues of mice lacking MKP5. Mechanistically, MKP5 inhibits the activation of hepatic stellate cells (HSCs) and hepatocyte apoptosis through the regulation of the IRE/XBP1 pathway. Based on these findings, we developed PLGA-MKP5 nanoparticles coated with a mesenchymal stem cell membrane (MSCM). Our results demonstrated that MSCM-PLGA-MKP5 was most effective in attenuating hepatic inflammation and fibrosis in murine models by modulating the IRE/XBP1 axis. This study contributes to the current understanding of the pathogenesis of hepatic fibrosis, suggesting that the targeted delivery of MKP5 via a nano-delivery system may represent a promising therapeutic approach to treat hepatic fibrosis.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"741"},"PeriodicalIF":10.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750387","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":"Oral creatine-modified selenium-based hyaluronic acid nanogel mediated mitochondrial energy recovery to drive the treatment of inflammatory bowel disease.","authors":"Manxiu Huai, Mingliang Pei, Jie Chen, Xiaoyan Duan, Yun Zhu, Fan Yang, Wensong Ge","doi":"10.1186/s12951-024-03007-0","DOIUrl":"10.1186/s12951-024-03007-0","url":null,"abstract":"<p><p>The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HA_Se-Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HA_Se-Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HA_Se-Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HA_Se-Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"740"},"PeriodicalIF":10.6,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750476","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":"Sele-targeted siRNA liposome nanoparticles inhibit pathological scars formation via blocking the cross-talk between monocyte and endothelial cells: a preclinical study based on a novel mice scar model.","authors":"Luyu Li, Yong Wang, Jing Meng, Xue Wang, Xiaojin Wu, Yan Wo, Ying Shang, Zhen Zhang","doi":"10.1186/s12951-024-03003-4","DOIUrl":"10.1186/s12951-024-03003-4","url":null,"abstract":"<p><strong>Background: </strong>Pathological scars (PS) are one of the most common complications in patients with trauma and burns, leading to functional impairments and aesthetic concerns. Mechanical tension at injury sites is a crucial factor in PS formation. However, the precise mechanisms remain unclear due to the lack of reliable animal models.</p><p><strong>Results: </strong>We developed a novel mouse model, the Retroflex Scar Model (RSM), which induces PS by applying controlled tension to wounds in vivo. RNA sequencing identified significant transcriptome changes in RSM-induced scars. Elevated expression of E-Selectin (Sele) was observed in endothelial cells from both the RSM model and human PS (Keloid) samples. In vitro studies demonstrated that cyclic mechanical stretching (CMS) increased Sele expression, promoting monocyte adhesion and the release of pro-inflammatory factors. Single-cell sequencing analysis from the GEO database, complemented by Western blotting, immunofluorescence, and co-immunoprecipitation, confirmed the role of Sele-mediated monocyte adhesion in PS formation. Additionally, we developed Sele-targeted siRNA liposome nanoparticles (LNPs) to inhibit monocyte adhesion. Intradermal administration of these LNPs effectively reduced PS formation in both in vivo and in vitro studies.</p><p><strong>Conclusions: </strong>This study successfully established a reliable mouse model for PS, highlighting the significant roles of mechanical tension and chronic inflammation in PS formation. We identified Sele as a key therapeutic target and developed Sele-targeted siRNA LNPs, which demonstrated potential as a preventive strategy for PS. These findings provide valuable insights into PS pathogenesis and open new avenues for developing effective treatments for pathological scars.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"733"},"PeriodicalIF":10.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729698","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":"Multifunctional nanocomposites utilizing ruthenium (II) complex/manganese (IV) dioxide nanoparticle for synergistic reinforcing radioimmunotherapy.","authors":"Jian Peng, Dong-Ling Quan, Guang Yang, Lin-Tao Wei, Zhuan Yang, Zhi-Ying Dong, Yi-Ming Zou, Ying-Ke Hou, Jin-Xiang Chen, Lin Lv, Bin Sun","doi":"10.1186/s12951-024-03013-2","DOIUrl":"10.1186/s12951-024-03013-2","url":null,"abstract":"<p><p>Radiotherapy (RT) stands as a frontline treatment modality in clinical breast oncology, yet challenges like ROS reduction, high toxicity, non-selectivity, and hypoxia hinder efficacy. Additionally, RT administered at different doses can induce varying degrees of radioimmunotherapy. High doses of radiation (>10 Gy) may result in immune suppression, while moderate doses (4-10 Gy), although capable of mitigating the immune suppression caused by high-dose radiation, are often insufficient in effectively killing tumor cells. Therefore, enhancing the generation of ROS and ameliorating the tumor hypoxic immune-suppressive microenvironment at moderate radiation doses could potentially drive radiation-induced immune responses, offering a fundamental solution to the limitations of RT. In this study, a novel multifunctional nanoplatform, RMLF, integrating a Ru (II) complex into folate-functionalized liposomes with BSA-MnO₂ nanoparticles was proposed. Orthogonal experimental optimization enhances radiosensitization via increasing accumulation in cancer cells, elevating ROS, and contributing to a dual enhancement of the cGAS-STING-dependent type I IFN signaling pathway, aimed to overcome the insufficient DAMPs typically seen in the conventional RT at 4 Gy. Such a strategy effectively activated cytotoxic T lymphocytes for infiltration into tumor tissues and promoted the polarization of tumor-associated macrophages from the M2 to M1 phenotype, substantially bolstering immune memory responses. This pioneering approach represents the first use of a ruthenium complex in radioimmunotherapy, activating the cGAS-STING pathway to amplify immune responses, overcome RT resistance, and extend immunotherapeutic potential.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"735"},"PeriodicalIF":10.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729697","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":"Targeting the tumor microenvironment with biomaterials for enhanced immunotherapeutic efficacy.","authors":"Yekai Feng, Qinglai Tang, Bin Wang, Qian Yang, Yuming Zhang, Lanjie Lei, Shisheng Li","doi":"10.1186/s12951-024-03005-2","DOIUrl":"10.1186/s12951-024-03005-2","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex system characterized by low oxygen, low pH, high pressure, and numerous growth factors and protein hydrolases that regulate a wide range of biological behaviors in the tumor and have a profound impact on cancer progression. Immunotherapy is an innovative approach to cancer treatment that activates the immune system, resulting in the spontaneous killing of tumor cells. However, the therapeutic efficacy of these clinically approved cancer immunotherapies (e.g., immune checkpoint blocker (ICB) therapies and chimeric antigen receptor (CAR) T-cell therapies) is far from satisfactory due to the presence of immunosuppressive TMEs created in part by tumor hypoxia, acidity, high levels of reactive oxygen species (ROS), and a dense extracellular matrix (ECM). With continuous advances in materials science and drug-delivery technologies, biomaterials hold considerable potential for targeting the TME. This article reviews the advances in biomaterial-based targeting of the TME to advance our current understanding on the role of biomaterials in enhancing tumor immunity. In addition, the strategies for remodeling the TME offer enticing advantages; however, the represent a double-edged sword. In the process of reshaping the TME, the risk of tumor growth, infiltration, and distant metastasis may increase.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"737"},"PeriodicalIF":10.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739716","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":"Dual-modal overcoming of physical barriers for improved photodynamic cancer therapy via soft organosilica nanocapsules.","authors":"Wei Lu, Yang Li, Xiaojun Zhang, Ning Wang, Dong Chen, Yatong Zhao, Guang Li, Xuzhi Shi, Xiaobo Ma, Xiaodan Su, Feng Wang, Chuqiang Shu, Kun Chen","doi":"10.1186/s12951-024-02945-z","DOIUrl":"10.1186/s12951-024-02945-z","url":null,"abstract":"<p><p>Amidst the burgeoning field of cancer nanomedicine, dense extracellular matrices and anomalous vascular structures in the tumor microenvironment (TME) present substantial physical barriers to effective therapeutic delivery. These physical barriers hinder the optimal bioavailability of nanomedicine. Here, we propose a pioneering dual-modal strategy for overcoming physical barriers via soft organosilica nanocapsules (SMONs). Hyaluronidase-modified flexible spheres work by degrading the extracellular matrix and utilizing their flexible characteristics to enhance penetration into deeper layers. Compared with their stiff counterparts, the SMONs show diminished Young's modulus, then the inherent softness of the SMONs confers distinct advantages, and significantly augmented cellular internalization within 4T1 cells, leading to an amplified in vitro photodynamic therapeutic effect. Furthermore, hyaluronidase-functionalized SMONs (SMONs-HAase) exhibit enhanced tumor penetration in 3D spheroids. Post incorporation of the photosensitizer chlorin e6, when administered intravenously, these soft organosilica nanocapsules amplify the efficacy of photodynamic therapy. In addition, RNA-seq analysis of SMONs-HAase-Ce6 shows it alters gene expression, degrading the extracellular matrix and impairing mitochondrial function. To sum up, this work elucidates the potential of a dual-modal strategy, highlighting the promise of SMONs in overcoming TME physical barriers and optimizing therapeutic outcomes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"734"},"PeriodicalIF":10.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729696","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":"Dendritic mesoporous silica-delivered siRNAs nano insecticides to prevent Sogatella furcifera by inhibiting metabolic detoxification and reproduction.","authors":"Changwei Gong, Wei Wang, Yanxin Ma, Xiaoxu Zhan, Anchun Peng, Jian Pu, Jizhi Yang, Xuegui Wang","doi":"10.1186/s12951-024-02966-8","DOIUrl":"10.1186/s12951-024-02966-8","url":null,"abstract":"<p><strong>Background: </strong>Migratory insect infestation caused by Sogatella furcifera is a serious threat to rice production. The most effective method available for S. furcifera control is intensive insecticide spraying, which cause widespread resistance. RNA interference (RNAi) insecticides hold enormous potential in managing pest resistance. However, the instability and the poor efficiency of cross-kingdom RNA trafficking are key obstacles for the application in agricultural pest management.</p><p><strong>Methods: </strong>We present dendritic mesoporous silica nanoparticles (DMSNs)-based nanocarrier for delivering siRNA and nitenpyram to inhibit the metabolic detoxification and development of S. furcifera, thereby preventing its proliferation.</p><p><strong>Results: </strong>This nano complex (denoted as N@UK-siRNA/DMSNs) significantly enhanced the stability of siRNA (efficacy lasting 21 days) and released cargos in GSH or planthopper bodily fluid with a maximum release rate of 84.99%. Moreover, the released UK-siRNA targeting two transcription factors (Ultraspiracle and Krüppel-homolog 1) downregulated the developmental genes Ultraspiracle (0.09-fold) and Krüppel-homolog 1 (0.284-fold), and downstream detoxification genes ABC SfABCH4 (0.016-fold) and P450 CYP6FJ3 (0.367-fold).</p><p><strong>Conclusion: </strong>The N@UK-siRNA/DMSNs inhibited pest development and detoxification, significantly enhancing susceptibility to nitenpyram to nanogram level (LC₅₀ is 250-252 ng/mL), resulting in a 5.37-7.13-fold synergistic ratio. This work proposes a comprehensive management strategy for controlling S. furcifera to ensure the green and safe production of rice.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"736"},"PeriodicalIF":10.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739646","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":"Time-series metabolomic analysis revealed altered metabolism of cynomolgus monkeys after injecting exosomes.","authors":"Xinmei Hu, Cancan Wang, Yu Xiao, Peng Jiang, Dongxing Huang, Liang-Cheng Li, Zhongquan Qi","doi":"10.1186/s12951-024-02976-6","DOIUrl":"10.1186/s12951-024-02976-6","url":null,"abstract":"<p><strong>Background: </strong>Recent years, exosomes have been increasing used to treat diseases, but there is little research on how exosomes affect the metabolism of the body after entering. Therefore, in this study, we discussed the changes of metabolic spectrum and determined the differentially expressed metabolites in the serum of cynomolgus monkeys after injecting exosomes. Six cynomolgus monkeys were divided into control group and exosomes group. After intravenous injection of exosomes, the peripheral blood serum of cynomolgus monkeys was collected at baseline, day 1, day 7 and day 14 respectively. An ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based non-targeted metabolomics platform was used to detect the metabolites. The metabolic spectra of two groups of cynomolgus monkeys were identified and compared, and the time series changes of metabolites in exosomes were described.</p><p><strong>Results: </strong>The results showed that there was significant difference in metabolic spectrum between the two groups. 45, 114, 49, 39 differentially expressed metabolites were identified in baseline, day 1, day 7, and day 14, respectively. 6-hydroxydopamine, a metabolite related to the regulation of nerve function, was also found. Tryptophan metabolism, choline metabolism in cancer, porphyrin and chlorophyll metabolism were involved in day 1. Sphingolipid metabolism and histidine metabolism were involved in day 7. Three pathways, including choline metabolism, sphingolipid metabolism and biotin metabolism in cancer were involved in day 14. Through time series analysis, it was found that the level of propionylcarnitine and biliverdin increased on day 1 after inoculation with exosomes, while the level of hippuric acid decreased. These changes of immune-related metabolites suggested that exosomes might participate in the immunoregulation reaction after entering the body of cynomolgus monkeys.</p><p><strong>Conclusions: </strong>In our current study, we found that exosomes injected intravenously affect the changes of metabolites and metabolic pathways in cynomolgus monkeys. Intravenous injection of exosomes may affect the metabolite 6-hydroxydopamine, sphingolipid metabolic pathway, and choline metabolic in cancer pathway, which is of some significance for the treatment of Parkinson's disease. In addition, exosomes may also affect the immune-related metabolites in vivo, such as propionylcarnitine, biliverdin, hippuric acid metabolites, as well as tryptophan metabolism pathway, sphingolipid metabolism pathway involved in immune regulation, which is of great significance for the future study of immune-regulatory mechanisms of exosomes.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"732"},"PeriodicalIF":10.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715942","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}