{"title":"Gut microbiota contributes to polystyrene nanoplastics-induced fetal growth restriction by disturbing placental nicotinamide metabolism.","authors":"Yijing He, Qiao Li, Qinfeng Sun, Heran Li, Tianhang Yu, Miaoyu Chen, Genkui Zhang, Biao Zhang, Weihan Wang, Shiqiang Ju","doi":"10.1186/s12951-025-03650-1","DOIUrl":"10.1186/s12951-025-03650-1","url":null,"abstract":"<p><p>Polystyrene nanoplastics (PS-NPs) are ubiquitous in the environment, eliciting significant concerns about their possible risks to human health, especially reproductive health. Various reproductive toxicities of PS-NPs have been reported, however, information regarding the effects of PS-NPs exposure during pregnancy on offspring development and the underlying mechanisms remains limited. In this study, pregnant mice were orally administered PS-NPs (approximately 100 nm in diameter) at different concentrations (1, 10, and 100 mg/kg/day) for 17.5 consecutive days, from gestational day (GD) 0.5 to GD 17.5. The relevant samples were collected on GD 18.5 to investigate the intergenerational effects. The results indicated that PS-NPs induced placental injury and metabolic abnormalities, leading to adverse pregnancy outcomes. Specifically, PS-NPs exposure observably reduced the levels of nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD<sup>+</sup>) in the placenta, resulting in decreased ATP production, increased oxidative stress and ferroptosis. Meanwhile, PS-NPs disrupted the maternal gut microbiome, specifically manifested as a reduction in Lactobacillus levels and abundances of norank_f_Muribaculaceae, Turicibacter, Alloprevotella, Parabacteroides and Ruminococcus. Fecal microbial transplant (FMT) experiments demonstrated that the microbiota from PS-NPs-administered pregnant mice could similarly induce intestinal barrier damages and placental injury. Treatment with NAM effectively mitigated disruptions in placental metabolism and reversed the adverse pregnancy outcomes caused by PS-NPs. These findings highlight the novel role of the gut microbiota in PS-NPs-induced placental injury and adverse pregnancy outcomes, and suggest that NAM could serve as a promising preventative strategy against this intergenerational damage caused by PS-NPs.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"561"},"PeriodicalIF":12.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835349","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}
Kingsley Miyanda Tembo, Xiaohui Wang, Mansoor Bolideei, Qianrui Liu, Farouk Baboni, Mohammad Javad Mehran, Fei Sun, Cong-Yi Wang
{"title":"Exploring the bioactivity of MicroRNAs Originated from Plant-derived Exosome-like Nanoparticles (PELNs): current perspectives.","authors":"Kingsley Miyanda Tembo, Xiaohui Wang, Mansoor Bolideei, Qianrui Liu, Farouk Baboni, Mohammad Javad Mehran, Fei Sun, Cong-Yi Wang","doi":"10.1186/s12951-025-03602-9","DOIUrl":"10.1186/s12951-025-03602-9","url":null,"abstract":"<p><p>Exosomes, nano-sized extracellular vesicles, facilitate intercellular communication by transferring biomolecules such as microRNAs (miRNAs), which are key regulators of gene expression. While mammalian-derived exosomes (MDEs) have shown therapeutic promise, their clinical application has been limited by challenges such as immune-related toxicities, low yield and high production costs. In contrast, plant-derived exosome-like nanoparticles (PELNs) offer a sustainable, biocompatible, and cost-effective alternative, encapsulating a diverse array of bioactive miRNAs with significant therapeutic potential. Studies have demonstrated the ability of PELN-derived miRNAs in cross-kingdom communication, effectively transferring into mammalian cells, where they modulate disease-related pathways, including cancer, inflammation, metabolism, and neurodegeneration. This review explores the bioactivity of plant-derived miRNAs, highlighting their role as novel therapeutic agents. The study explores the bioactivity and potential mechanisms by which these miRNAs influence human cellular processes, focusing on their ability to regulate gene expression in different tissues. Additionally, the study examines recent advances in PELN research, emphasizing their potential for clinical translation in precision medicine, and highlights challenges and future prospects in harnessing the therapeutic capabilities of these bioactive miRNAs. This review underscores the potential of PELNs to revolutionize therapeutic strategies, offering a sustainable, biocompatible, and cost-effective platform for targeted miRNA delivery, paving the way for innovative interventions leveraging nature's own nanocarriers.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"563"},"PeriodicalIF":12.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835348","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":"Radiocleavable rare-earth nanoactivators targeting over-expressed folate receptors induce mitochondrial dysfunction and remodel immune suppressive microenvironment in pancreatic cancer.","authors":"Tanvi Gupta, Shang-Rung Wu, Li-Chan Chang, Forn-Chia Lin, Yan-Shen Shan, Chen-Sheng Yeh, Wen-Pin Su","doi":"10.1186/s12951-025-03657-8","DOIUrl":"10.1186/s12951-025-03657-8","url":null,"abstract":"<p><p>Pancreatic cancer is a fatal cancer with poor prognosis and survival rate, often diagnosed usually in the advanced stage of disease. The conventional methods are usually considered for surgery or chemotherapy, and neo-adjuvant therapies have improved the survival rate in the patients. Folic acid plays a crucial role in the synthesis, metabolism, and repair of DNA; thereby, it is considered one of the biomolecules for cancer-targeted therapy for highly expressed receptors to overcome poor vasculature and dense tumor stroma, as in pancreatic cancer. This study strategizes for improving the therapeutic efficacy of pancreatic cancer via folate receptor-guided nanoparticles. The conjugation of folic acid (FA) to the LiYF<sub>4</sub>:Ce<sup>3+</sup>nanoparticles (SCNP-FA) with the photocleavage chemical molecule; firstly enters the cells through receptor-mediated endocytosis and then, releases FA intracellularly upon the trigger of radiation in a controlled manner. This nano-based approach induces ferroptosis to provoke immunogenic cell death (ICD) with higher generation of reactive oxygen species (ROS) and accumulation of lipid peroxides. It shows an abundant damage to the mitochondria and a decrease in mitochondrial membrane potential (MMP) upon treatment. This targeted therapy remodels the immunosuppressive tumor microenvironment and releases damage-associated molecular patterns (DAMPs) to initiate an immune response. These findings reveal the anti-tumor response with folate receptor-guided nanoparticles in pancreatic cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"562"},"PeriodicalIF":12.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835350","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}
Yonghui Su, Dongqun Guo, Yinghao Liang, Tuerdimaimaiti Meiheriban, Siyu Chen, Qian Tang, Xiqian Chen, Yan Huang, Jianqiao Zhong, Zongjunlin Liu
{"title":"Tumor-microenvironment triggered Mn-Gd based nanosystem for breast carcinoma suppression via synergistic radiotherapy and glutathione-depleting along with glucose oxidase combination enhanced Ros storm.","authors":"Yonghui Su, Dongqun Guo, Yinghao Liang, Tuerdimaimaiti Meiheriban, Siyu Chen, Qian Tang, Xiqian Chen, Yan Huang, Jianqiao Zhong, Zongjunlin Liu","doi":"10.1186/s12951-025-03636-z","DOIUrl":"10.1186/s12951-025-03636-z","url":null,"abstract":"<p><strong>Background: </strong>Cancer treatment commonly involves radiation as a primary therapy, affecting nearly two-thirds of patients. The use of combination therapies is gaining traction, with the aim of achieving synergistic effects through the pharmacological interactions of multiple treatments.</p><p><strong>Methods and results: </strong>In this study, we present a Mn-Gd-based bimetallic nanoplatform resembling a virus, designed with a rough surface for anchoring glucose oxidase enzymes (GOx) and coating with extracellular vehicles (EVs) on the outer layer (VMn-Gd@GOx-EVs). This platform enables a synergistic approach by combining radiation therapy (RT) with oxidative therapy. The nanoplatform offers four key benefits: targeted delivery to tumors through EVs, Mn and Gd ion release triggered by the tumor microenvironment, GOx-induced generation of H<sub>2</sub>O<sub>2</sub> and acidic conditions for subsequent Fenton-like reactions, and relief from hypoxia to enhance RT.</p><p><strong>Conclusion: </strong>Remarkably, the VMn-Gd@GOx-EVs platform effectively induces cell death in breast carcinoma models both in vitro and in vivo by harnessing the combined effects of RT and reactive oxygen species (ROS) generated by Mn ion catalysis under X-ray irradiation. Moreover, with its magnetic resonance imaging capabilities, this multi-functional diagnostic and therapeutic platform shows significant potential for clinical tumor treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"557"},"PeriodicalIF":12.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821602","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}
Lin Ma, Xiaoxue Yang, Xiaoyao Huang, Hao Guo, Zihan Li, Siyuan Fan, Han Qin, Fanhui Meng, Peisheng Liu, Xinyu Wang, Meiling Wu, Kun Xuan, Anqi Liu
{"title":"Dynamic three-dimensional culture enhances tunneling nanotubes-mediated mitochondrial transfer in mesenchymal stromal cells to accelerate wound healing.","authors":"Lin Ma, Xiaoxue Yang, Xiaoyao Huang, Hao Guo, Zihan Li, Siyuan Fan, Han Qin, Fanhui Meng, Peisheng Liu, Xinyu Wang, Meiling Wu, Kun Xuan, Anqi Liu","doi":"10.1186/s12951-025-03655-w","DOIUrl":"10.1186/s12951-025-03655-w","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have shown promise in treating various diseases, and optimizing their therapeutic potential is a crucial objective in MSCs-based clinical applications. The microenvironment, particularly three-dimensional (3D) culture systems, plays a pivotal role in regulating the fate determination and enhancing the therapeutic potential of MSCs. Currently, the mechanisms governing the interactions between MSCs cultured in a dynamic 3D system and host recipient cells remain incompletely understood. MSCs transfer mitochondria to influence the fate of recipient cells, with tunneling nanotubes (TNTs) being the primary method. However, whether MSCs cultured under dynamic 3D conditions transfer mitochondria via TNTs to exert therapeutic effects remains to be elucidated. This study developed a dynamic 3D culture system for stem cells from human exfoliated deciduous teeth (SHED), a type of MSCs, utilizing gelatin microcryogel microcarriers and stirred tank bioreactor. A mouse model of full-thickness skin defects was employed to validate the enhanced therapeutic efficacy of SHED cultured under dynamic 3D conditions. Co-culture experiments with SHED and endothelial cells demonstrated that the dynamic 3D culture conditions empower the MSCs to transfer mitochondria via TNTs, thereby promoting angiogenesis. This research provides novel insights into the mechanisms underlying wound healing acceleration by SHED cultured under dynamic 3D conditions and offers a new strategy for developing MSCs transplantation applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"559"},"PeriodicalIF":12.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821599","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":"Exo-hydrogel therapy: a revolutionary approach to managing diabetic complications.","authors":"Yiming Meng, Jing Sun, Yushu Ma, Cuicui Kong","doi":"10.1186/s12951-025-03621-6","DOIUrl":"10.1186/s12951-025-03621-6","url":null,"abstract":"<p><p>This review systematically examines the transformative potential of Exosome-hydrogel (Exo-gel) composite systems in combating diabetic complications, with a particular emphasis on their macromolecular interactions and therapeutic implications. By synergistically integrating the bioactive cargo of Exos with the structural tunability of polysaccharide-based hydrogels, this advanced biomaterial platform addresses critical limitations in conventional therapies through the spatiotemporally controlled delivery of regenerative factors. We highlight how the dynamic interplay between natural biopolymers and exosomal surface proteins enhances extracellular matrix (ECM) remodeling while maintaining bioactive stability, a crucial advancement for chronic diabetic conditions. A comprehensive analysis reveals that Exo-gel systems demonstrate therapeutic efficacy in three key pathological contexts: (1) neural regeneration via Schwann cell modulation, (2) angiogenesis restoration through VEGF/VEGFR signaling pathways, and (3) chronic wound healing mediated by macrophage polarization. Our critical appraisal of preclinical evidence positions Exo-gel technology as a paradigm-shifting approach in diabetes care, offering solutions to current challenges in sustained drug delivery and targeted tissue regeneration, while outlining future translational pathways for bioengineered therapeutic systems.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"558"},"PeriodicalIF":12.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821600","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}
Jana Ramon, Cláudio Pinheiro, Charysse Vandendriessche, Estefanía Lozano-Andrés, Herlinde De Keersmaecker, Deep Punj, Juan C Fraire, Edward Geeurickx, Marca H M Wauben, Pieter Vader, Roosmarijn E Vandenbroucke, An Hendrix, Stephan Stremersch, Stefaan C De Smedt, Koen Raemdonck, Kevin Braeckmans
{"title":"Pre-formation loading of extracellular vesicles with exogenous molecules using photoporation.","authors":"Jana Ramon, Cláudio Pinheiro, Charysse Vandendriessche, Estefanía Lozano-Andrés, Herlinde De Keersmaecker, Deep Punj, Juan C Fraire, Edward Geeurickx, Marca H M Wauben, Pieter Vader, Roosmarijn E Vandenbroucke, An Hendrix, Stephan Stremersch, Stefaan C De Smedt, Koen Raemdonck, Kevin Braeckmans","doi":"10.1186/s12951-025-03640-3","DOIUrl":"10.1186/s12951-025-03640-3","url":null,"abstract":"<p><p>Despite the natural capacity of extracellular vesicles (EVs) to encapsulate intracellular compounds and transfer these to nearby or distant recipient cells, the intentional loading of EVs with cargo molecules remains a challenging endeavor. Pre-formation EV loading (i.e., during EV biogenesis), offers advantages compared to post-formation loading (i.e., after EV isolation), as EV integrity and composition are minimally perturbed. Pre-formation EV loading is primarily achieved through the genetic engineering of the producer cell, which is time consuming and not very flexible regarding the types of molecules that can be incorporated into EVs. In this work, we investigated the possibility of loading cargo molecules into EVs by delivering the cargo directly into the cytosol of the producer cells, which can subsequently be encapsulated into EVs as they are formed. For the cytosolic delivery of cargo molecules, we evaluated the use of photoporation. This membrane disruption technology has been demonstrated to successfully deliver a broad range of cargo molecules into virtually any cell type, while minimally impacting the cell's normal functioning and homeostasis. As a proof-of-concept, we delivered fluorescently labeled dextran macromolecules and anti-EGFP nanobodies into HEK293T cells genetically engineered with gag-EGFP fusion proteins, which are shuttled into EVs. Colocalization of cargo and EGFP fluorescence in secreted EVs can then serve as a convenient readout for successful EV loading. We established that photoporation had minimal impact on EV characteristics such as concentration, size, zeta potential and the enrichment of EV tetraspanin membrane surface molecules. We found that using EGFP-targeted nanobodies resulted in up to 53% loaded EVs (relative to the amount of EGFP EVs), while non-targeted dextran molecules produced on average 12% loaded EVs (relative to the amount of EGFP EVs). These results highlight the promise of photoporation for pre-formation loading of EVs.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"556"},"PeriodicalIF":12.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799314","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}
Shulin Qin, Kexin Chen, Shanfeng Chen, Xin Chen, Yi Hu, Wenlong Peng, Zhenyu Pan, Xin Ji, Peng Pang, Qiaoming Luo, Wen Liu
{"title":"N6-methyladenosine-modified circDCP2 promotes carbon black nanoparticle-induced malignancy in human bronchial epithelial cells via PI3K-AKT pathway and macrophage homeostasis.","authors":"Shulin Qin, Kexin Chen, Shanfeng Chen, Xin Chen, Yi Hu, Wenlong Peng, Zhenyu Pan, Xin Ji, Peng Pang, Qiaoming Luo, Wen Liu","doi":"10.1186/s12951-025-03632-3","DOIUrl":"10.1186/s12951-025-03632-3","url":null,"abstract":"<p><p>Long-term exposure to environmental carbon black nanoparticles (CBNP) has been shown to increase the risk of pulmonary malignancies. However, the role of epigenetic regulation, particularly circular RNAs (circRNAs), in this process remains poorly understood. Using whole transcriptome and RNA sequencing, we identified that circDCP2 was upregulated in CBNP-transformed cells and clinically lung cancer tissues. Moreover, circDCP2 was found to promote tumor progression both in vitro and in vivo. Mechanistically, N6-methyladenosine (m<sup>6</sup>A) modification of circDCP2 promotes the transcriptional upregulation of cyclin D1 (CCND1) by interacting with heterogeneous nuclear ribonucleoprotein A2/B1 (HnRNPA2B1), thereby activating the PI3K-AKT signaling pathway and promoting malignant transformation. Additionally, circDCP2 facilitates the IGF2BP3-JAK-STAT signaling pathway, which promotes the reprogramming of tumor-associated macrophages (TAMs) into the M2-type TAMs via cytokines secretion, contributing to the formation of an immunosuppressive microenvironment that further accelerates tumorigenesis and progression. Our research demonstrates that circDCP2 functions as an important regulator in promoting CBNP-induced lung carcinogenesis and may serve as a potential diagnostic biomarker and a promising therapeutic target for lung cancer patients.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"555"},"PeriodicalIF":12.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794736","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}