International Journal of Nanomedicine最新文献

{"title":"Exosomes Derived From Human Mesenchymal Stem Cells Mitigate Follicular Interstitial Cell Ferroptosis via the miR-26a-5p/PTEN/GPX4 Axis in Rats with Chemotherapy-Induced Premature Ovarian Insufficiency.","authors":"Juntong Chen, Xingyu Huo, Maojiao Qian, Qian Xue, Yu He, Pengzhan Xu, Yueming Wang, Xiaoxuan Tang, Qianqian Luo, Hongchu Bao, Yanlian Xiong","doi":"10.2147/IJN.S532207","DOIUrl":"https://doi.org/10.2147/IJN.S532207","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a persistent condition in young women characterized by early follicular development disorders and reduced fertility. Research has found that exosomes derived from human umbilical mesenchymal stem cells (hUCMSC-Exo) have significant tissue repair effects. This study aims to investigate the therapeutic effect and potential molecular mechanism of hUCMSC-Exo on POI.</p><p><strong>Methods: </strong>In vivo experiments were conducted by intraperitoneally injecting the chemotherapy drug cyclophosphamide (CTX) to establish a 14-day POI rat model. Serum hormone levels were measured using an enzyme-linked immunosorbent assay, and changes in ovarian tissue structure were analyzed using hematoxylin-eosin (HE) staining. Perls staining and transmission electron microscopy were used to assess changes in ovarian ferroptosis. In vitro experiments involved exposing theca interna cells (TICs) treated with CTX to normal and miR-26a-5p inhibitor-treated hUCMSC-Exo. The expression changes of PTEN, Nrf2, and GPX4, which are associated with ferroptosis, were analyzed using immunofluorescence, Western blot, and quantitative reverse-transcription polymerase chain reaction.</p><p><strong>Results: </strong>hUCMSC-Exo intervention can significantly repair the ovarian tissue structure and functional abnormalities in the model rats, especially ferroptosis. Further bioinformatics analysis revealed that the inhibition of the PTEN/GPX4 pathway-mediated ferroptosis in TICs might be the main mechanism through which exosomes exert their regulatory/therapeutic effects. In vitro experiments, where exosome miR-26a-5p was inhibited, further confirmed that the delivery of miR-26a-5p is crucial for the regulatory effect of exosomes.</p><p><strong>Conclusion: </strong>In conclusion, our results suggest that hUCMSC-Exos alleviates POI-related dysfunction of ovarian structure and function. The mechanism could be related to the transfers of miR-26a-5p and suppression of PTEN/GPX4 axis signaling-mediated autophagy of TICs. It provides a new perspective for developing treatment methods for patients with metabolic abnormalities related to POI.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10195-10212"},"PeriodicalIF":6.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Hyaluronic Acid Nanobioconjugates Impair CD44-Signaling for Effective Treatment Against Obesity: A Review of Comparison with Other Actors.","authors":"Daniel Ejim Uti, Wilson Achu Omang, Esther Ugo Alum, Okechukwu Paul-Chima Ugwu, Margaret Amieibi Wokoma, Rowland Inalegwu Oplekwu, Item Justin Atangwho, Godwin Eneji Egbung","doi":"10.2147/IJN.S529250","DOIUrl":"10.2147/IJN.S529250","url":null,"abstract":"<p><p>CD44, a key hyaluronic acid (HA) receptor, has emerged as a central mediator of adipose tissue inflammation, remodeling, and insulin resistance in obesity. Its overexpression in obese adipose depots promotes leukocyte infiltration, pro-inflammatory signaling, and extracellular matrix dysregulation processes that underlie metabolic dysfunction. This review explores the therapeutic relevance of targeting the HA-CD44 axis by synthesizing data primarily from preclinical studies, with emerging evidence from early clinical investigations. A narrative review methodology was employed to assess and compare therapeutic modalities, highlighting advances in molecular targeting, drug delivery systems, and metabolic interventions. We focus on two primary therapeutic classes: small molecules and nanobioconjugates. Small molecules, such as curcumin, metformin, and CD44 antagonists, offer systemic modulation and accessibility but are limited by their low tissue specificity and potential side effects. In contrast, HA-functionalized nanobioconjugates, including liposomes, PLGA nanoparticles, dendrimers, and exosomes, enable targeted delivery to adipose tissue, prolonged drug release, and reduced systemic toxicity. These nanosystems have demonstrated superior modulation of CD44 signaling, adipose inflammation, and glucose homeostasis in obesity models. Emerging strategies such as monoclonal antibodies, GLP-1 analogs, gene-editing tools (eg, CRISPR/Cas9), microbiome modulators, and brown adipose tissue (BAT) activators are also discussed. A comparative analysis indicates that nanobioconjugates offer the highest targeting precision, while small molecules remain advantageous in terms of cost and ease of administration. However, biologics and gene therapies face challenges related to delivery and scalability. Collectively, current evidence predominantly preclinical supports the HA-CD44 axis as a promising therapeutic target in obesity. Integrated approaches combining nanotechnology with molecular inhibitors and biologics could offer a multifaceted strategy for managing metabolic disease.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10101-10126"},"PeriodicalIF":6.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Hypoxic Microenvironment By Nanoformulation For Effective T Cell Therapy In Mice Model.","authors":"Xiaoyu Feng, Hao Zhu, Jingwen Shen, Yan Wang, Shutong Liu, Xinjie Chen, Yaohua Ke, Dinghu Zhang, Lixia Yu, Baorui Liu, Qin Liu, Hao Wang, Yanhong Chu","doi":"10.2147/IJN.S522504","DOIUrl":"https://doi.org/10.2147/IJN.S522504","url":null,"abstract":"<p><strong>Introduction: </strong>Adoptive cell therapy (ACT) has emerged as a powerful strategy for eliciting tumor regression. However, its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME). We developed a tumor microenvironment-responsive mesoporous silica nanosphere (MSN) formulation co-loaded with the immunostimulant imiquimod (R837), zinc peroxide (ZnO₂), and manganese peroxide (MnO₂) to alleviate hypoxia and enhance dendritic cell (DC)-mediated antitumor immunity.</p><p><strong>Methods: </strong>The immunostimulatory efficacy of our nanoparticles was evaluated in vitro using DC activation assays and in vivo in an H22 murine hepatocellular carcinoma model. Flow cytometry was employed to assess immune cell populations in tumors and lymph nodes, while immunofluorescence microscopy was used to analyze tumor hypoxia and T cell infiltration.</p><p><strong>Results: </strong>The oxygen-generating MSN formulation effectively alleviated intratumoral hypoxia, promoted DC maturation (CD80⁺CD86⁺), and facilitated effector CD8⁺ T cell infiltration into tumors. In vivo, co-administration of the nanoformulation with ACT led to enhanced tumor suppression and systemic antitumor immune responses without evident toxicity to major organs.</p><p><strong>Conclusion: </strong>This oxygen-producing immunomodulatory nanoplatform remodels the immunosuppressive TME and significantly enhances the efficacy of ACT in solid tumors, offering a promising strategy for overcoming current barriers in T cell-based immunotherapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10073-10087"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Active-Passive Dual-Targeted Drug-Loaded Micelle Nanoparticles with Modified Dopamine Molecules for Efficient Anti-Tumor Therapy.","authors":"ZhiFeng Chen, WenLing Liu, ZiJian Zeng, ZhiHong Yan, LiHeng Ma, Yi Liu, XianShuo Cao","doi":"10.2147/IJN.S528334","DOIUrl":"https://doi.org/10.2147/IJN.S528334","url":null,"abstract":"<p><strong>Purpose: </strong>This study designed a dopamine derivative integrating active targeting and pH-responsive borate ester bond-mediated passive targeting to construct drug delivery systems for tumor-targeted drug delivery, thus improving antitumor drug bioavailability and expanding the application of dopamine in drug delivery.</p><p><strong>Methods: </strong>Nuclear magnetic resonance and Fourier transform infrared spectrometry were used to determine the structures of Man-PBA-DAO and Man-2PBA-DAO. Hydrodynamic diameter measurements confirmed the pH responsiveness of the targeting nanoparticles in different pH media over 12 hours. Nanoparticle toxicity was assessed using the MTT assay. Cellular uptake of the targeting nanoparticles was evaluated using flow cytometry and fluorescence microscopy. High-performance liquid chromatography (HPLC) was employed to quantify curcumin content.</p><p><strong>Results: </strong>Covalent binding of mannose molecules to the dopamine derivative molecule allowed it to specifically target A549 cells with mannose receptors. More importantly, a significantly accelerated drug release (about 62% at pH=5.0) at low pH values was achieved by regulating the number of acidic-responsive borate bonds in polymer main chains. As a result, due to active targeting of mannose and passive targeting of acid response, Curcumin-loaded nanoparticles offer remarkably enhanced inhibiting efficiency against A549 cells at a low concentration of 6.25 μg/mL.</p><p><strong>Conclusion: </strong>The dopamine derivative Man-2PBA-DAO-constructed dual active-passive targeting nano micelles enabled precise delivery and controllable release of Cur, offering new prospects for dopamine-based drug delivery in lung cancer treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10089-10100"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Using Different Cationic Polymers on the Formation of Efficient Lipopolyplexes for pDNA Delivery.","authors":"Giulia Anderluzzi, Tasnim Mohamed, Giorgia Moschetti, Elena Del Favero, Loris Rizzello, Valerio Magnaghi, Silvia Franzé, Francesco Cilurzo","doi":"10.2147/IJN.S513568","DOIUrl":"https://doi.org/10.2147/IJN.S513568","url":null,"abstract":"<p><strong>Purpose: </strong>Lipopolyplexes (LPP), i.e. hybrid ternary complexes of cationic polymers, nucleic acids and liposomes, represent a second-generation non-viral vector aiming to overcome the limitations of the first-generation polyplexes and lipoplexes like in vivo toxicity and ineffective transfection efficiency. Although their potential has already been proven in vitro and in vivo, lipopolyplexes are still poorly explored as gene delivery systems. Here, we provid evidence of the effect of lipopolyplexes composition on their physicochemical features, cytotoxicity, and biological activity (i.e. cell uptake, endosomal escape, and transfection efficiency).</p><p><strong>Methods: </strong>Lipopolyplexes were prepared by either bulk mixing or a two-step microfluidic process consisting of i) the formation of polyplexes by complexing a plasmid DNA encoding the green fluorescence protein with a panel of cationic polymers (either chitosan, poly-L-lysine (PLL) or polyethyleneimine (PEI)) followed by ii) the formation of the ternary complex by mixing polyplexes with neutral liposomes. The optimal polymer/DNA/lipid Nitrogen/Phosphate ratios and microfluidic operating parameters (volume ratio and total flow rate (TFR) were preliminarily defined to obtain lipopolyplexes with desired properties.</p><p><strong>Results: </strong>The optimized conditions led to obtain lipopolyplexes with a mean diameter of ~180 nm, a PDI < 0.2 and a slightly positive or neutral z-potential. FRET, SAXS and Cryo-EM analyses demonstrated the formation of a ternary complex in which the type of polymer dictated particles' structure. Lipopolyplexes displayed negligible toxicity in vitro, while promoting higher protein expression compared to the corresponding polyplexes and control 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) lipoplexes. Moreover, despite the three lipopolyplexes displaying similar uptake kinetics, those made of PEI showed the highest endosomolytic activity and promoted the most effective DNA transfection.</p><p><strong>Conclusion: </strong>Overall, this study demonstrates that lipopolyplexes are a valid platform for pDNA delivery, with PEI lipopolyplexes being the best performing formulation, and that the type of cationic polymer plays a major role in the nanoparticles intercellular trafficking.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10021-10041"},"PeriodicalIF":6.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Integrated Approach: Plant-Mediated Synthesis, in vitro and in silico Evaluation of Silver Nanoparticles for Breast Cancer and Bacterial Therapies.","authors":"Sahar S Alghamdi, Haifa A Alhaidal, Afrah E Mohammed, Arwa Alsubait, Maali D Alshammari, Lamis Alsaqer, Shahad Saleem Alzahrani, Fai Alanazi, Layan Basel Al Tuhayni, Rizwan Ali, Shaden Alharbi, Bader Hazazi, Mona E AlEnazi, Zeyad I Alehaideb","doi":"10.2147/IJN.S516723","DOIUrl":"https://doi.org/10.2147/IJN.S516723","url":null,"abstract":"<p><strong>Background and aim: </strong>Nanotechnology offers a promising approach to address breast cancer and bacterial resistance, two critical global health challenges. This study synthesized silver nanoparticles (AgNPs) using extracts from <i>Rhazya stricta</i> (<i>R.S). Calotropis procera</i> (<i>C.P)</i>. and <i>Calligonum comosum</i> (<i>C.C)</i> to evaluate their potential as novel therapeutic agents.</p><p><strong>Materials and methods: </strong>AgNP synthesis was achieved via co-precipitation, and their characterization was performed using various techniques. Cytotoxicity was assessed using the MTT assay against multiple breast cancer cell lines (KAIMRC2, MDA-MB231, MCF-7) and a non-malignant control (MCF-10A). Antimicrobial activity was evaluated using a well diffusion assay against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. LC-MS identified several bioactive metabolites, which were further analyzed in silico computational analysis to predict their anti-cancer and antibacterial properties.</p><p><strong>Results: </strong>The resulting AgNPs demonstrated significant cytotoxicity against breast cancer cells with minimal toxicity to normal cells, and potent antibacterial activity. Specifically, <i>R.S</i>.-AgNPs showed strongest activity against MDA-MB-231, <i>C.P</i>.-AgNPs against MCF-7, and <i>C.C</i>.-AgNPs against KAIMRC-2. Promising lead metabolites, including 1-Acetylaspidospermidine, Apigenin-7-o-glucoside, and Chlorogenic acid, were identified, suggesting potential for development as novel oral anti-cancer and antibacterial agents.</p><p><strong>Conclusion: </strong>Further research focusing on the optimization and preclinical development of these identified metabolites is warranted to explore their translational potential as oral anti-cancer and antibacterial agents.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"10043-10071"},"PeriodicalIF":6.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Key Anti-Oncolytic Therapeutics Are Effective In Cancer Treatment?","authors":"Luyi Ye, Meng Gao, Yue Chen, Yuting Zhu, Jilong Wang, Zhangquan Wang","doi":"10.2147/IJN.S531849","DOIUrl":"https://doi.org/10.2147/IJN.S531849","url":null,"abstract":"<p><p>Oncolytic virus (OVs) therapy has emerged as a promising modality in cancer immunotherapy, attracting growing attention for its multifaceted mechanisms of tumor elimination. However, its efficacy as a monotherapy remains constrained by physiological barriers, limited delivery routes, and suboptimal immune activation. Phototherapy, an innovative and rapidly advancing cancer treatment technology, can mitigate these limitations when used in conjunction with OVs, enhancing viral delivery, amplifying tumor destruction, and boosting antitumor immune responses. This review provides the first comprehensive analysis of synergistic integration of OVs with both photodynamic therapy (PDT) and photothermal therapy (PTT). It also explores their applications in optical imaging-guided diagnosis and optogenetically controlled delivery. Furthermore, it discusses emerging strategies involving biomimetic virus or viroid-based vectors in conjunction with phototherapy, and delves into the immunomodulatory mechanisms of this combinatorial approach. While promising in preclinical models, these combined strategies are still largely in early-stage research. Challenges such as limited light penetration, delivery efficiency, and safety concerns remain to be addressed for clinical translation. Consequently, the integration of OV therapy and phototherapy represents a compelling strategy in cancer treatment, offering significant promise for advancing precision oncology and next-generation immunotherapies.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"9999-10019"},"PeriodicalIF":6.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Cell Repression by TNF-α-Primed Exosomes Accelerate T2DM Wound Healing Through miR-146a-5p/TXNIP/NLRP3 Axis.","authors":"Jiaqi Li, Xiaoxuan Lin, Jinyang Wang, Xuanyi Li, Zhengchuan Zhang, Leyang Ji, Rongcheng Yu, Xiaoxing Kou, Yang Yang","doi":"10.2147/IJN.S522994","DOIUrl":"https://doi.org/10.2147/IJN.S522994","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) impairs wound healing due to hyperglycemia-induced immune dysfunction. Dendritic cells (DCs) in the skin are crucial for wound healing but are adversely affected by hyperglycemic microenvironment. Exosomes derived from mesenchymal stem cells (MSC-exos), especially adipose-derived MSCs (ADSCs) with higher accessibility, have shown potential for immune regulation. However, their yield and efficacy can be limited. This study aims to explore the effects of TNF-α-preconditioned ADSCs-exos (T-exos) on restoring DC function and accelerating wound healing in T2DM.</p><p><strong>Methods: </strong>T-exos were isolated from ADSCs pretreated with TNF-α. The regulatory effects of T-exos on DC immune responses under high glucose conditions were assessed. Subsequently, the roles of DCs treated with T-exos in diabetic wound healing were evaluated. Finally, the mechanism underlying T-exos-mediated regulation of DCs was investigated in detail.</p><p><strong>Results: </strong>Under high glucose conditions, T-exos suppressed DC activation, as evidenced by reduced CD80/CD86 expression and NLRP3 inflammasome activity. In vivo studies showed that T-exos promoted wound closure in T2DM mice, enhancing collagen deposition, angiogenesis, and fibroblast proliferation. Mechanistically, TNF-α enriched miR-146a-5p in exosomes, which targeted TXNIP to inhibit NLRP3 inflammasome activation in DCs. Knockdown of miR-146a-5p abolished these effects in vitro and the therapeutic effect of T-exos on wound healing in vivo.</p><p><strong>Conclusion: </strong>This study elucidates a previously unrecognized role for T-exos in effectively regulating DC activation through the miR-146a-5p/TXINP/NLRP3 axis, which in turn modulates the NLRP3 inflammasome pathway. By synergistically dampening inflammation and enhancing tissue repair, T-exos exhibit significant potential for clinical application in T2DM wounds.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"9963-9980"},"PeriodicalIF":6.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-Mineralization By Polyelectrolyte Nanocomposite For Effective Against Dentin Hypersensitivity.","authors":"Wenqi Gao, Chunyan Wan, Zeyu Han, Caiyun Li, Yanan Zhao, Lingshuang Liu","doi":"10.2147/IJN.S530148","DOIUrl":"https://doi.org/10.2147/IJN.S530148","url":null,"abstract":"<p><strong>Introduction: </strong>Dentin hypersensitivity (DH) causes considerable discomfort in many patients due to its characteristic symptoms, which primarily arise from exposed dentinal tubules (DTs). DTs also serve as a pathway for bacterial invasion. Therefore, a treatment that both effectively occludes DTs and prevents caries is needed.</p><p><strong>Methods: </strong>Polyaspartic acid (Pasp) and carboxymethyl chitosan (CMC) were combined with amorphous calcium phosphate (ACP) to develop PCA. PCA was compared with three polyelectrolyte complexes (PA, CA, PC). Recombinant collagen models assessed the mineralization-promoting effect of PCA, whereas DH models evaluated its ability to occlude DTs. The sealing performance and surface hardness of PCA-treated dentin discs were assessed by airtightness and hardness tests. Antibacterial effects were analyzed using live-dead staining, bacterial adherence assays, and colony-forming unit (CFU) counts. Biocompatibility was evaluated by live-dead cell staining, CCK-8 assays, and hemolysis tests.</p><p><strong>Results: </strong>PCA contains ACP clusters approximately 2 nm in diameter and achieves effective intrafibrillar mineralization within 5 days. PCA completely covers the collagen fibers on the dentin surface and occludes the DTs. The remineralized dentin demonstrates excellent resistance to friction and acid exposure. PCA treatment significantly restores the airtightness and mechanical strength of demineralized dentin. Moreover, PCA exhibits strong antibacterial activity against Streptococcus mutans (<i>S. mutans</i>). Biocompatibility tests confirm favorable safety profiles.</p><p><strong>Conclusion: </strong>This study demonstrates the dual function of PCA in DH management and caries prevention by occluding DTs and providing antibacterial protection, supporting its potential for clinical application.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"9981-9998"},"PeriodicalIF":6.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of Three Nanoparticle Vaccines Targeting the Prefusion F Protein of Respiratory Syncytial Virus: Immunogenicity and Protective Efficacy.","authors":"Jie Jiang, Hongqiao Hu, Lei Cao, Naiying Mao, Zhen Zhu, Na Wang, Yuqing Shi, Hai Li, Yan Zhang","doi":"10.2147/IJN.S523340","DOIUrl":"https://doi.org/10.2147/IJN.S523340","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the immunogenic potential of three different nanoparticle (NP) platforms for respiratory syncytial virus (RSV) prefusion (pre-F) protein vaccines.</p><p><strong>Methods: </strong>Three NP platforms-24-mer ferritin (Fe), 60-mer lumazine synthase (LuS), and 120-subunit I53-50-were engineered to display RSV pre-F trimers (DS2) via SpyTag-SpyCatcher (ST-SC) conjugation (DS2-Fe, DS2-LuS) or direct genetic fusion (DS2-I53-50). The assembled particles were characterized using size-exclusion chromatography (SEC), SDS-PAGE, electron microscopy (EM), and dynamic light scattering (DLS). Antigenicity was evaluated using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) with prefusion-specific neutralizing antibodies. Immunogenicity and protective efficacy were evaluated in BALB/c mice following a prime-boost immunization, with analyses of humoral and cellular immune responses as well as post-challenge protection.</p><p><strong>Results: </strong>All three NP platforms successfully displayed the DS2 antigen while preserving its prefusion conformation. Notably, DS2-I53-50 demonstrated superior assembly quality and particle homogeneity relative to DS2-Fe and DS2-LuS. Compared to soluble DS2, all three DS2-NPs exhibited enhanced binding affinity (7- to 12-fold increase) to prefusion-specific antibodies (D25, AM14). In vivo, all DS2-NPs elicited higher levels of RSV-specific neutralizing antibodies and induced a more balanced Th1/Th2 immune response, with DS2-I53-50 generating significantly greater neutralizing antibody titers (1.7- to 2.4-fold increase) against both prototype RSV strains (LONG, 18537) and circulating genotypes (ON1, BA9). Immune cell profiling further revealed that all three DS2-NPs enhanced germinal center formation, facilitated follicular dendritic cell recruitment, and expanded memory T cell populations. Following RSV challenge, all DS2-NPs vaccines conferred significant protection, evidenced by accelerated weight recovery, reduced lung viral loads, and mitigated pulmonary pathology. Among them, DS2-I53-50 provided the most robust protection, achieving a 3.7-log reduction in viral titers and minimal lung pathology.</p><p><strong>Conclusion: </strong>NP platforms significantly enhanced the immunogenicity of RSV DS2 antigens, with DS2-I53-50 eliciting the strongest immune responses and protective efficacy. These findings underscore the potential of rationally designed NP-based vaccines for RSV.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"9945-9961"},"PeriodicalIF":6.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}