Pub Date : 2025-05-11DOI: 10.1016/j.nano.2025.102828
Kamil Szeliski PhD , Zuzanna Fekner MSc , Damian Kasiński MSc , Marta Rasmus MSc , Filip Kowalski MD, PhD , Milena Świtońska Assoc. Prof. , Katarzyna Sierakowska Assoc. Prof. , Tomasz Drewa Prof. , Marta Pokrywczyńska Prof.
Diagnosing prostate cancer (PCa) and risk-stratifying patients remains challenging, as PSA-based methods lack precision for active surveillance (AS) decision-making. Extracellular vesicles (EVs) are membranous nano-sized vesicles released by all types of cells and may contain potentially interesting material for diagnostic procedures for PCa.
This study analyzed surface markers and miRNA profiles of medium-sized plasma EVs (mEVs) from 24 PCa patients using nanoflow cytometry and miRNA profiling. The ratio of PSMA+ EVs to PSMA+CD9+ EVs differed significantly between AS and non-AS patients. Additionally, miR-99a-5p, miR-125b-5p, miR-145-5p, and miR-365a-3p levels were higher in non-AS patients.
These findings suggest that plasma-derived PSMA+ mEVs originate from the prostate and may serve as biomarkers for PCa progression. Nanoflow cytometry-based analysis of EV surface markers combined with miRNA profiling provides a novel, non-invasive alternative to PSA measurements. This approach could improve risk stratification and decision-making for AS patients, potentially leading to better outcomes.
{"title":"The potential of plasma-derived medium-sized extracellular vesicles as a biopsy alternative for active surveillance decisions in prostate Cancer","authors":"Kamil Szeliski PhD , Zuzanna Fekner MSc , Damian Kasiński MSc , Marta Rasmus MSc , Filip Kowalski MD, PhD , Milena Świtońska Assoc. Prof. , Katarzyna Sierakowska Assoc. Prof. , Tomasz Drewa Prof. , Marta Pokrywczyńska Prof.","doi":"10.1016/j.nano.2025.102828","DOIUrl":"10.1016/j.nano.2025.102828","url":null,"abstract":"<div><div>Diagnosing prostate cancer (PCa) and risk-stratifying patients remains challenging, as PSA-based methods lack precision for active surveillance (AS) decision-making. Extracellular vesicles (EVs) are membranous nano-sized vesicles released by all types of cells and may contain potentially interesting material for diagnostic procedures for PCa.</div><div>This study analyzed surface markers and miRNA profiles of medium-sized plasma EVs (mEVs) from 24 PCa patients using nanoflow cytometry and miRNA profiling. The ratio of PSMA+ EVs to PSMA+CD9+ EVs differed significantly between AS and non-AS patients. Additionally, miR-99a-5p, miR-125b-5p, miR-145-5p, and miR-365a-3p levels were higher in non-AS patients.</div><div>These findings suggest that plasma-derived PSMA+ mEVs originate from the prostate and may serve as biomarkers for PCa progression. Nanoflow cytometry-based analysis of EV surface markers combined with miRNA profiling provides a novel, non-invasive alternative to PSA measurements. This approach could improve risk stratification and decision-making for AS patients, potentially leading to better outcomes.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"67 ","pages":"Article 102828"},"PeriodicalIF":4.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-03DOI: 10.1016/j.nano.2025.102827
Bongsu Jung Ph.D , Fazal-Ur-Rehman Bhatti Ph.D , Harisankeerth Mummareddy M.S , Youngjoo Kim M.A , Sang-Hyug Park Ph.D , Hongsik Cho Ph.D, MBA
Inflammation plays a significant role in the pathogenesis of knee post-traumatic osteoarthritis (PTOA) characterized by damage to cartilage and surrounding tissues that results in loss of physiological function. This inflammation is mainly regulated by NF-κB pathway. The TPCA-1 can inhibit IκB kinase (IKK) β in NF-κB pathway. Here, we optimized the delivery of TPCA-1 to the damaged knee joint via targeted nanosomes and examined its effects in a mouse model of PTOA.
PTOA was induced in mice through a modified cyclic mechanical loading method. Mice were divided into groups receiving vehicle, TPCA-1 solution, or TPCA-1-loaded nanosomes. A concentration of 100 μM TPCA-1 was used based on preliminary studies. Control groups included untreated and vehicle-treated animals. Treatment efficacy was assessed using in vivo imaging, serum biochemical assays, gene expression analysis of cartilage tissues, histopathology, and behavioral analysis.
Mechanical loading induced significant knee joint damage in the model. TPCA-1 nanosomes notably attenuated the adverse effects of loading, outperforming both the vehicle and TPCA-1-solution in reducing inflammation. Notably, serum levels of total NO and LDH were significantly lower in the TPCA-1-nanosome group. Inflammation, as indicated by MMP13 and IL1β gene expression, was substantially reduced. Enhanced cartilage preservation and function were confirmed through IVIS imaging, histological assessments, and improved behavior metrics.
The targeted delivery of TPCA-1 via nanosomes effectively inhibits the NF-κB pathway, leading to significant reductions in inflammation and cartilage damage in a PTOA mouse model. This strategy demonstrates potential as a therapeutic intervention for managing inflammation and preserving joint health in osteoarthritis.
{"title":"Targeted nanosome delivery of TPCA-1 for modulating inflammation in a mouse model of post-traumatic osteoarthritis","authors":"Bongsu Jung Ph.D , Fazal-Ur-Rehman Bhatti Ph.D , Harisankeerth Mummareddy M.S , Youngjoo Kim M.A , Sang-Hyug Park Ph.D , Hongsik Cho Ph.D, MBA","doi":"10.1016/j.nano.2025.102827","DOIUrl":"10.1016/j.nano.2025.102827","url":null,"abstract":"<div><div>Inflammation plays a significant role in the pathogenesis of knee post-traumatic osteoarthritis (PTOA) characterized by damage to cartilage and surrounding tissues that results in loss of physiological function. This inflammation is mainly regulated by NF-κB pathway. The TPCA-1 can inhibit IκB kinase (IKK) β in NF-κB pathway. Here, we optimized the delivery of TPCA-1 to the damaged knee joint via targeted nanosomes and examined its effects in a mouse model of PTOA.</div><div>PTOA was induced in mice through a modified cyclic mechanical loading method. Mice were divided into groups receiving vehicle, TPCA-1 solution, or TPCA-1-loaded nanosomes. A concentration of 100 μM TPCA-1 was used based on preliminary studies. Control groups included untreated and vehicle-treated animals. Treatment efficacy was assessed using in vivo imaging, serum biochemical assays, gene expression analysis of cartilage tissues, histopathology, and behavioral analysis.</div><div>Mechanical loading induced significant knee joint damage in the model. TPCA-1 nanosomes notably attenuated the adverse effects of loading, outperforming both the vehicle and TPCA-1-solution in reducing inflammation. Notably, serum levels of total NO and LDH were significantly lower in the TPCA-1-nanosome group. Inflammation, as indicated by MMP13 and IL1β gene expression, was substantially reduced. Enhanced cartilage preservation and function were confirmed through IVIS imaging, histological assessments, and improved behavior metrics.</div><div>The targeted delivery of TPCA-1 via nanosomes effectively inhibits the NF-κB pathway, leading to significant reductions in inflammation and cartilage damage in a PTOA mouse model. This strategy demonstrates potential as a therapeutic intervention for managing inflammation and preserving joint health in osteoarthritis.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"67 ","pages":"Article 102827"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-30DOI: 10.1016/j.nano.2025.102825
M. Tommy Gambles PhD , Isaac Kendell BS , Jiahui Li PharmD , Kyle Spainhower MSc , Douglas Sborov MS, MD , Shawn Owen PhD , Alex Stark PhD , David Bearss PhD , Jiyuan Yang PhD , Jindřich Kopeček PhD, DSc
Contemporary T-cell immunotherapies, despite impressive targeting precision, are hindered by aberrant cytokine release and restrictive targeting stoichiometry. We introduce a two-component T-cell immunotherapy targeting B-cell malignancies: Multi-Antigen T-Cell Hybridizers (MATCH). This split antibody technology differs from current therapies by separating cancer cell-targeting components from T cell-engaging components. We demonstrate that this two-component structure facilitates tunable T-cell activation. αCD19 and αCD20 MATCH, administered in two steps, are both compared to the clinical standard bispecific antibody, blinatumomab. In vitro two-dimensional dose analysis and cytokine release data indicate MATCH improves cancer clearance with reduced cytokine release. Cytolytic mechanisms of action are evaluated. αCD20 MATCH anti-cancer efficacy is assayed using a human lymphoma murine model. Decreasing T-cell engager dose 10-fold yields comparable efficacy to non-reduced doses. Ultimately, this split-antibody paradigm may enhance antigen targeting while reducing cytokine release, with such safety and efficacy advantages augmented by the future possibility of multi-antigen targeting with MATCH.
{"title":"Two-component T-cell immunotherapy enables antigen pre-targeting to reduce cytokine release without forfeiting efficacy","authors":"M. Tommy Gambles PhD , Isaac Kendell BS , Jiahui Li PharmD , Kyle Spainhower MSc , Douglas Sborov MS, MD , Shawn Owen PhD , Alex Stark PhD , David Bearss PhD , Jiyuan Yang PhD , Jindřich Kopeček PhD, DSc","doi":"10.1016/j.nano.2025.102825","DOIUrl":"10.1016/j.nano.2025.102825","url":null,"abstract":"<div><div>Contemporary T-cell immunotherapies, despite impressive targeting precision, are hindered by aberrant cytokine release and restrictive targeting stoichiometry. We introduce a two-component T-cell immunotherapy targeting B-cell malignancies: Multi-Antigen T-Cell Hybridizers (MATCH). This split antibody technology differs from current therapies by separating cancer cell-targeting components from T cell-engaging components. We demonstrate that this two-component structure facilitates tunable T-cell activation. αCD19 and αCD20 MATCH, administered in two steps, are both compared to the clinical standard bispecific antibody, blinatumomab. <em>In vitro</em> two-dimensional dose analysis and cytokine release data indicate MATCH improves cancer clearance with reduced cytokine release. Cytolytic mechanisms of action are evaluated. αCD20 MATCH anti-cancer efficacy is assayed using a human lymphoma murine model. Decreasing T-cell engager dose 10-fold yields comparable efficacy to non-reduced doses. Ultimately, this split-antibody paradigm may enhance antigen targeting while reducing cytokine release, with such safety and efficacy advantages augmented by the future possibility of multi-antigen targeting with MATCH.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"67 ","pages":"Article 102825"},"PeriodicalIF":4.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-28DOI: 10.1016/j.nano.2025.102821
Donya Esmaeilpour MSc , Ehsan Nazarzadeh Zare PhD , Mahnaz Hassanpur MSc , Farooq Sher PhD , Mika Sillanpää PhD
Integrating artificial intelligence (AI) with nanomedicine is transforming Theranostics, driving advances in biosensing, bioimaging, genomics, diagnostics, and treatment. This review highlights the latest advancements in AI-driven nanomedicine, focusing on its transformative impact on healthcare. AI-integrated biosensors offer ultra-sensitive, real-time biomaterial detection, reducing false positives by 40 %. In bioimaging, AI algorithms improve resolution to 10 nm, particularly in gold nanoparticles (AuNP)-based imaging. AuNPs, leveraging surface plasmon resonance (SPR), act as contrast agents for early disease detection. AI accelerates genomic analysis, increasing sequencing accuracy by 30 %, enhancing biomarker identification for personalized medicine. AI powered diagnostics ensure rapid, non-invasive pathogen detection within 30 min with 95 % accuracy. AI-driven drug delivery systems enable precise, controlled release, reducing side effects by 20 %. This review explores AI-enhanced AuNPs in biosensing, bioimaging, genomics, diagnostics, and therapy while addressing challenges like scalability, biocompatibility. AI's role in Nanomedicine underscores its potential to revolutionize personalized medicine and future healthcare innovations.
{"title":"Comparative examination of the chemistry and biology of AI-driven gold NPs in Theranostics: New insights into biosensing, bioimaging, genomics, diagnostics, and therapy","authors":"Donya Esmaeilpour MSc , Ehsan Nazarzadeh Zare PhD , Mahnaz Hassanpur MSc , Farooq Sher PhD , Mika Sillanpää PhD","doi":"10.1016/j.nano.2025.102821","DOIUrl":"10.1016/j.nano.2025.102821","url":null,"abstract":"<div><div>Integrating artificial intelligence (AI) with nanomedicine is transforming Theranostics, driving advances in biosensing, bioimaging, genomics, diagnostics, and treatment. This review highlights the latest advancements in AI-driven nanomedicine, focusing on its transformative impact on healthcare. AI-integrated biosensors offer ultra-sensitive, real-time biomaterial detection, reducing false positives by 40 %. In bioimaging, AI algorithms improve resolution to 10 nm, particularly in gold nanoparticles (AuNP)-based imaging. AuNPs, leveraging surface plasmon resonance (SPR), act as contrast agents for early disease detection. AI accelerates genomic analysis, increasing sequencing accuracy by 30 %, enhancing biomarker identification for personalized medicine. AI powered diagnostics ensure rapid, non-invasive pathogen detection within 30 min with 95 % accuracy. AI-driven drug delivery systems enable precise, controlled release, reducing side effects by 20 %. This review explores AI-enhanced AuNPs in biosensing, bioimaging, genomics, diagnostics, and therapy while addressing challenges like scalability, biocompatibility. AI's role in Nanomedicine underscores its potential to revolutionize personalized medicine and future healthcare innovations.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"67 ","pages":"Article 102821"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1016/j.nano.2025.102826
Xinyi Mao BS , Yun Lan BS , Fangzhou Lou Undergraduate, Zhun Zhang MSc, Qi Jin BS, Yuandi Jia BS, Ye Li PhD
In recent years, graphene oxide (GO) has emerged as a promising nanocarrier for targeted mRNA delivery. However, the detailed molecular mechanisms governing its transmembrane transport remain poorly understood. Here, we employ molecular simulations to systematically investigate how membrane surface tension and binding configurations influence the transmembrane behavior of GO-mRNA nanocomplexes. Our findings reveal a membrane tension-dependent entry pathway that nanocomplex entry cell from adhesion/penetration to endocytosis, suggesting a potential mechanism for tumor cell drug resistance development. Furthermore, we demonstrate distinct transmembrane dynamics process for three predominant GO-mRNA binding modes, exhibiting variations in translocation velocity, penetration depth, and resultant membrane deformation. These computational insights provide crucial theoretical guidance for engineering optimized mRNA delivery carrier, potentially advancing the biomedical application of GO-based nanoplatforms in gene therapy and precision oncology.
{"title":"Molecular understanding of transmembrane transport of mRNA carried by graphene oxide: Effect of membrane tension","authors":"Xinyi Mao BS , Yun Lan BS , Fangzhou Lou Undergraduate, Zhun Zhang MSc, Qi Jin BS, Yuandi Jia BS, Ye Li PhD","doi":"10.1016/j.nano.2025.102826","DOIUrl":"10.1016/j.nano.2025.102826","url":null,"abstract":"<div><div>In recent years, graphene oxide (GO) has emerged as a promising nanocarrier for targeted mRNA delivery. However, the detailed molecular mechanisms governing its transmembrane transport remain poorly understood. Here, we employ molecular simulations to systematically investigate how membrane surface tension and binding configurations influence the transmembrane behavior of GO-mRNA nanocomplexes. Our findings reveal a membrane tension-dependent entry pathway that nanocomplex entry cell from adhesion/penetration to endocytosis, suggesting a potential mechanism for tumor cell drug resistance development. Furthermore, we demonstrate distinct transmembrane dynamics process for three predominant GO-mRNA binding modes, exhibiting variations in translocation velocity, penetration depth, and resultant membrane deformation. These computational insights provide crucial theoretical guidance for engineering optimized mRNA delivery carrier, potentially advancing the biomedical application of GO-based nanoplatforms in gene therapy and precision oncology.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"67 ","pages":"Article 102826"},"PeriodicalIF":4.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-23DOI: 10.1016/j.nano.2025.102824
Shaul D. Cemal PhD , Gila Kazimirsky MSc , Yana Shadkchan PhD , Lakshmanan Eswaran PhD , Rinat Abramovitch Prof. , Natalie Abudi PhD , Maria L. Cuestas Prof. , Nir Osherov Prof. , Gerardo Byk Prof.
Biodegradable polymers have gained attention for controlled drug delivery due to their potential for sustained release. Herein, a novel series of cross-linked, narrow size nanohydrogels (NHGs) with tunable sizes (20-500 nm), devoid of toxicity, and suitable for diverse biological applications were developed. These NHGs are synthesized via a thermo-responsive self-assembly process followed by confined polymerization. Ester cross-linkers were introduced into the polymeric backbone to enhance biodegradability. The NHGs comprise ideal candidates for drug delivery due to their long circulation in blood after iv administration. The anti-oxidant curcumin and the antifungal drug amphotericin B (AmB) as hydrophobic drug models were successfully loaded. The AmB-loaded NHGs showed improved antifungal activity against clinical isolates of molds and yeasts and markedly reduced morbidity in murine models inoculated with lethal doses of the pathogenic mold Candida albicans as compared to the commercial AmB formulation Fungizone. The NHGs thereby offer a versatile platform for controlled drug release.
{"title":"Biocompatible narrow size nanohydrogels for drug delivery","authors":"Shaul D. Cemal PhD , Gila Kazimirsky MSc , Yana Shadkchan PhD , Lakshmanan Eswaran PhD , Rinat Abramovitch Prof. , Natalie Abudi PhD , Maria L. Cuestas Prof. , Nir Osherov Prof. , Gerardo Byk Prof.","doi":"10.1016/j.nano.2025.102824","DOIUrl":"10.1016/j.nano.2025.102824","url":null,"abstract":"<div><div>Biodegradable polymers have gained attention for controlled drug delivery due to their potential for sustained release. Herein, a novel series of cross-linked, narrow size nanohydrogels (NHGs) with tunable sizes (20-500 nm), devoid of toxicity, and suitable for diverse biological applications were developed. These NHGs are synthesized <em>via</em> a thermo-responsive self-assembly process followed by confined polymerization. Ester cross-linkers were introduced into the polymeric backbone to enhance biodegradability. The NHGs comprise ideal candidates for drug delivery due to their long circulation in blood after <em>iv</em> administration. The anti-oxidant curcumin and the antifungal drug amphotericin B (AmB) as hydrophobic drug models were successfully loaded. The AmB-loaded NHGs showed improved antifungal activity against clinical isolates of molds and yeasts and markedly reduced morbidity in murine models inoculated with lethal doses of the pathogenic mold <em>Candida albicans</em> as compared to the commercial AmB formulation Fungizone. The NHGs thereby offer a versatile platform for controlled drug release.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"66 ","pages":"Article 102824"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-21DOI: 10.1016/j.nano.2025.102822
Monique Macedo Coelho MSc , Isabela Beatriz Cabacinha Nóbrega PhD , Lícia Torres PhD , Rebecca Vasconcellos Botelho de Medeiros PhD , Érika Costa de Alvarenga PhD , Luiz Orlando Ladeira PhD , Ana Maria Caetano Faria PhD , Cláudia Rocha Carvalho PhD , Raquel Alves Costa PhD
Oral tolerance suppresses immune responses, such as antibody production, following immunization with an antigen and adjuvant in animals previously exposed to the protein orally. Parenteral administration of orally tolerated antigens with alum adjuvants induces systemic effects that inhibit immune responses to unrelated antigens and enhance wound healing in mouse skin. This study investigated whether subcutaneous (s.c.) administration of gold nanoparticles conjugated with ovalbumin (AuNPs@OVA) could serve as an effective adjuvant in oral tolerance and promote ear lesion repair in mice. Male Swiss mice received a 5-day oral OVA treatment, followed by s.c. injections of AuNPs@OVA at the tail base 7 days later, with a secondary injection administered 20 days after the initial dose. Lesions were created on one ear during the primary injection. Transmission electron microscopy (TEM) confirmed a spherical morphology of the AuNPs, with an average diameter of approximately 6.84 nm. The findings demonstrated that AuNPs@OVA injections enhanced IgG1, IgG2a, and total anti-OVA antibody levels in non-tolerant mice. Immunization also increased leukocyte levels at the injection site. In OVA-tolerant mice, AuNPs@OVA elevated the percentage of TBET-expressing cells in the caudal lymph nodes but not in the spleen. Histological analysis revealed improved ear tissue remodeling in OVA-tolerant mice treated with AuNPs@OVA compared to other groups. These results indicate that AuNPs@OVA injections not only leverage the indirect effects of oral tolerance but also outperform Al(OH)3 as an adjuvant in promoting ear wound healing.
{"title":"Gold nanoparticles associated with ovalbumin as adjuvant in the indirect effects of oral tolerance improve ear wound healing in mice","authors":"Monique Macedo Coelho MSc , Isabela Beatriz Cabacinha Nóbrega PhD , Lícia Torres PhD , Rebecca Vasconcellos Botelho de Medeiros PhD , Érika Costa de Alvarenga PhD , Luiz Orlando Ladeira PhD , Ana Maria Caetano Faria PhD , Cláudia Rocha Carvalho PhD , Raquel Alves Costa PhD","doi":"10.1016/j.nano.2025.102822","DOIUrl":"10.1016/j.nano.2025.102822","url":null,"abstract":"<div><div>Oral tolerance suppresses immune responses, such as antibody production, following immunization with an antigen and adjuvant in animals previously exposed to the protein orally. Parenteral administration of orally tolerated antigens with alum adjuvants induces systemic effects that inhibit immune responses to unrelated antigens and enhance wound healing in mouse skin. This study investigated whether subcutaneous (s.c.) administration of gold nanoparticles conjugated with ovalbumin (AuNPs@OVA) could serve as an effective adjuvant in oral tolerance and promote ear lesion repair in mice. Male Swiss mice received a 5-day oral OVA treatment, followed by s.c. injections of AuNPs@OVA at the tail base 7 days later, with a secondary injection administered 20 days after the initial dose. Lesions were created on one ear during the primary injection. Transmission electron microscopy (TEM) confirmed a spherical morphology of the AuNPs, with an average diameter of approximately 6.84 nm. The findings demonstrated that AuNPs@OVA injections enhanced IgG1, IgG2a, and total anti-OVA antibody levels in non-tolerant mice. Immunization also increased leukocyte levels at the injection site. In OVA-tolerant mice, AuNPs@OVA elevated the percentage of TBET-expressing cells in the caudal lymph nodes but not in the spleen. Histological analysis revealed improved ear tissue remodeling in OVA-tolerant mice treated with AuNPs@OVA compared to other groups. These results indicate that AuNPs@OVA injections not only leverage the indirect effects of oral tolerance but also outperform Al(OH)3 as an adjuvant in promoting ear wound healing.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"66 ","pages":"Article 102822"},"PeriodicalIF":4.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-18DOI: 10.1016/j.nano.2025.102820
Xiaolan Wang MSc , Shuanglan Xu PhD , Qian Liu MSc , Xiulin Ye MSc , Huilin He BS , Xifeng Zhang MSc , Linna Chen BS , Jiao Yang MSc , Xiqian Xing MSc
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious vascular disease with hidden symptoms and rapid progression. Nanomaterials provide new ideas for the diagnosis and treatment of VTE due to their high specific surface area, biocompatibility and modifiability. Due to differences in the formation mechanism and location of arterial and venous thrombosis, targeted diagnosis and treatment strategies need to be developed. This review focuses on VTE and summarizes the latest progress and limitations of nanomaterials in diagnosis and treatment. In terms of diagnosis, nanomaterials can be used to prepare biosensors to detect thrombin, fibrin, etc., and can also enhance imaging contrast to improve diagnostic accuracy. In terms of treatment, nanocarriers can target and release anticoagulant/thrombolytic drugs, improving efficacy and reducing side effects. However, the limitations of nanomaterials require researchers to optimize their properties to achieve safe and efficient development of VTE diagnosis and treatment.
{"title":"Research progress on the application of nanomaterials in the diagnosis and treatment of venous thromboembolism","authors":"Xiaolan Wang MSc , Shuanglan Xu PhD , Qian Liu MSc , Xiulin Ye MSc , Huilin He BS , Xifeng Zhang MSc , Linna Chen BS , Jiao Yang MSc , Xiqian Xing MSc","doi":"10.1016/j.nano.2025.102820","DOIUrl":"10.1016/j.nano.2025.102820","url":null,"abstract":"<div><div>Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious vascular disease with hidden symptoms and rapid progression. Nanomaterials provide new ideas for the diagnosis and treatment of VTE due to their high specific surface area, biocompatibility and modifiability. Due to differences in the formation mechanism and location of arterial and venous thrombosis, targeted diagnosis and treatment strategies need to be developed. This review focuses on VTE and summarizes the latest progress and limitations of nanomaterials in diagnosis and treatment. In terms of diagnosis, nanomaterials can be used to prepare biosensors to detect thrombin, fibrin, etc., and can also enhance imaging contrast to improve diagnostic accuracy. In terms of treatment, nanocarriers can target and release anticoagulant/thrombolytic drugs, improving efficacy and reducing side effects. However, the limitations of nanomaterials require researchers to optimize their properties to achieve safe and efficient development of VTE diagnosis and treatment.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"66 ","pages":"Article 102820"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-18DOI: 10.1016/j.nano.2025.102823
Dhrumi Patel M-Pharm, Sarika Wairkar PhD
Morin (MOR) is a potent neuroprotective agent possessing exceptional antioxidant abilities. The significant challenges associated with MOR delivery are poor solubility and low permeability. The present work aims to develop nasal delivery of MOR using lyotropic liquid crystalline nanoparticles (LLCs). MOR LLCs were prepared via the hydrotrope method, and 3-factor, 2-level factorial design was chosen for optimization. The results indicated MOR LLCs exhibited cubic vesicular structure, were non-toxic to nasal mucosa, and depicted sustained in vitro release. Pharmacokinetic studies showed MOR LLCs resulted in 1.53-fold and 1.42-fold enhancement in area under the curve than plain MOR oral and nasal groups. The relative drug targeting efficiency and relative direct transport percentage were 1.99-fold and 1.14-fold higher for MOR LLCs than plain nasal MOR, representing efficient brain targeting via olfactory pathways. Nasal administration of MOR LLCs enhances brain targeting and offers a self-administration option for prolonged utilization to alleviate neurological conditions.
{"title":"Lyotropic liquid crystalline nanoparticles of morin: An approach to improve pharmacokinetics and brain disposition in rats via nose-to-brain pathway","authors":"Dhrumi Patel M-Pharm, Sarika Wairkar PhD","doi":"10.1016/j.nano.2025.102823","DOIUrl":"10.1016/j.nano.2025.102823","url":null,"abstract":"<div><div>Morin (MOR) is a potent neuroprotective agent possessing exceptional antioxidant abilities. The significant challenges associated with MOR delivery are poor solubility and low permeability. The present work aims to develop nasal delivery of MOR using lyotropic liquid crystalline nanoparticles (LLCs). MOR LLCs were prepared <em>via</em> the hydrotrope method, and 3-factor, 2-level factorial design was chosen for optimization. The results indicated MOR LLCs exhibited cubic vesicular structure, were non-toxic to nasal mucosa, and depicted sustained <em>in vitro</em> release. Pharmacokinetic studies showed MOR LLCs resulted in 1.53-fold and 1.42-fold enhancement in area under the curve than plain MOR oral and nasal groups. The relative drug targeting efficiency and relative direct transport percentage were 1.99-fold and 1.14-fold higher for MOR LLCs than plain nasal MOR, representing efficient brain targeting <em>via</em> olfactory pathways. Nasal administration of MOR LLCs enhances brain targeting and offers a self-administration option for prolonged utilization to alleviate neurological conditions.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"66 ","pages":"Article 102823"},"PeriodicalIF":4.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma, driven by defective immune surveillance and cancer-cell evasion, has rising morbidity and mortality due to solar radiation exposure and delayed diagnosis. Effective tumor opsonization and phagocytosis are needed, demanding new therapeutic formulations. Here, we demonstrate the efficacy of a novel lipid-coated glucose nanosphere (LGNP) formulation decorated with ovalbumin (OVA) and containing pCMV-MART-1 (MT-1), termed the nLOM vaccine. This vaccine elicits specific immune responses through bone marrow DC maturation and CD4+/CD8+ T-cell activation, targeting melanoma antigens. In preclinical studies using orthotopic B16-F10 melanoma cells in C57BL/6J mice, the vaccine induced significant infiltration of T lymphocytes into tumor tissues, reducing tumor progression. Robust immune responses were observed in the spleens and inguinal lymph nodes of vaccinated mice, characterized by elevated cytokine levels. These findings suggest that the nLOM vaccine could elicit durable immunogenicity against melanoma through enhanced antigen presentation and holds promise for clinical development as an effective immunotherapy.
{"title":"Melanoma immunotherapy by nanosphere-vaccine elicited CD4+ and CD8+ T-cell response for tumor regression","authors":"Kalpana Javvaji PhD , Venugopal Vangala PhD , Suresh Babu Sayana PhD , Bhanu Maturi MD , Keerti Bhamidipati PhD , Keith R. Brunt PhD , Sunil Misra PhD , Ramesh Kandimalla PhD , Nagaprasad Puvvada PhD","doi":"10.1016/j.nano.2025.102817","DOIUrl":"10.1016/j.nano.2025.102817","url":null,"abstract":"<div><div>Melanoma, driven by defective immune surveillance and cancer-cell evasion, has rising morbidity and mortality due to solar radiation exposure and delayed diagnosis. Effective tumor opsonization and phagocytosis are needed, demanding new therapeutic formulations. Here, we demonstrate the efficacy of a novel lipid-coated glucose nanosphere (LGNP) formulation decorated with ovalbumin (OVA) and containing pCMV-MART-1 (MT-1), termed the nLOM vaccine. This vaccine elicits specific immune responses through bone marrow DC maturation and CD4+/CD8+ T-cell activation, targeting melanoma antigens. In preclinical studies using orthotopic B16-F10 melanoma cells in C57BL/6J mice, the vaccine induced significant infiltration of T lymphocytes into tumor tissues, reducing tumor progression. Robust immune responses were observed in the spleens and inguinal lymph nodes of vaccinated mice, characterized by elevated cytokine levels. These findings suggest that the nLOM vaccine could elicit durable immunogenicity against melanoma through enhanced antigen presentation and holds promise for clinical development as an effective immunotherapy.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"66 ","pages":"Article 102817"},"PeriodicalIF":4.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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