International Journal of Nanomedicine最新文献

{"title":"Iron(III)-Quercetin Complex: In Vivo Acute Toxicity and Biodistribution of Novel MRI Agent.","authors":"Phattarawadee Innuan, Sarawut Kongkarnka, Atigan Thongtharb, Jiraporn Kantapan, Nathupakorn Dechsupa","doi":"10.2147/IJN.S496015","DOIUrl":"https://doi.org/10.2147/IJN.S496015","url":null,"abstract":"<p><strong>Background: </strong>The iron(III)-quercetin complex, known as \"IronQ\", is an innovative MRI contrast agent composed of one Fe(III) ion and two quercetin molecules. IronQ is efficiently internalized by cells, enabling T1-weighted MRI tracking. It has demonstrated therapeutic benefits in reducing inflammation in an intracerebral hemorrhage (ICH) mouse model and offers a safer alternative to gadolinium-based agents by avoiding cytotoxicity and genotoxicity. These properties make IronQ a promising candidate for safe and effective MRI contrast enhancement.</p><p><strong>Purpose: </strong>This study aims to further the development of IronQ as an MRI contrast agent by investigating its biodistribution, pharmacokinetics, and acute toxicity in a preclinical animal model.</p><p><strong>Methods: </strong>The relaxivity of IronQ was measured in water and whole blood phantoms. Acute toxicity was evaluated in Sprague Dawley rats administered single intraperitoneal doses of IronQ (75, 150, and 225 µmol Fe/kg BW) over a 14-day period. Pharmacokinetic studies were performed at a dose of 150 µmol Fe/kg BW, with blood iron content analyzed using ICP-OES. For in vivo biodistribution, SD rats were administered an intravenous dose of IronQ (225 µmol Fe/kg BW), followed by MR imaging using a 1.5 T scanner and subsequent tissue-ICP analysis.</p><p><strong>Results: </strong>The longitudinal relaxivity (r₁) of IronQ was measured to be 2.17 mm⁻¹s⁻¹ in ultrapure water and 3.56 mm⁻¹s⁻¹ in whole blood. Acute toxicity studies showed no mortality, morbidity, or significant biochemical changes, with histopathology confirming no irreversible organ damage. Pharmacokinetics revealed peak blood iron content at 1.1 hours post-administration and clearance within 24 hours. MRI demonstrated enhanced T1 signal intensity, particularly in the liver and kidney.</p><p><strong>Conclusion: </strong>These findings provide valuable insights into the safety, pharmacokinetics, and imaging efficacy of IronQ, highlighting its potential as a robust and biocompatible MRI contrast agent.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1303-1320"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189020","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 Procedural Overview of the Involvement of Small Molecules in the Nervous System in the Regulation of Bone Healing.","authors":"Xuyan Wei, Mucong Li, Jiaqian You, Jiaxin Luo, Jingjie Zhai, Jiameng Zhang, Jian Feng, Hanchi Wang, Yanmin Zhou","doi":"10.2147/IJN.S505677","DOIUrl":"https://doi.org/10.2147/IJN.S505677","url":null,"abstract":"<p><p>Clinically, a multitude of factors can contribute to the development of bone defects. In the process of bone healing, the nervous system plays a vital role in bone regeneration. Small molecules from the nervous system, such as neurotrophic factors and neuropeptides, have been found to stimulate osteoblast proliferation and differentiation by activating signaling pathways associated with bone calcification and angiogenesis. These small molecules play a crucial regulatory role at various stages of bone healing. The systematic release mechanism of small molecules within the nervous system through diverse bone tissue engineering materials holds significant clinical implications for the controlled regulation of the bone healing process. This review provides an overview of the involvement of various nervous system small molecules at different stages of bone healing and discusses their regulatory mechanisms, aiming to establish a theoretical foundation for programmed regulation in bone regeneration and design of replacement materials in bone tissue engineering.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1263-1284"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189075","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":"<i>N</i>-2-Hydroxypropyl Trimethyl Ammonium Chloride Chitosan-Aluminum Nano-Adjuvant Elicit Strong Immune Responses in Porcine Epidemic Diarrhea Inactivated Vaccine.","authors":"Zheng Jin, Jiali Liu, Sihan Guo, Shangen Xu, Xiaochen Gong, Chunjing Zhang, Kai Zhao","doi":"10.2147/IJN.S496077","DOIUrl":"https://doi.org/10.2147/IJN.S496077","url":null,"abstract":"<p><strong>Background: </strong>Porcine epidemic diarrhea virus (PEDV) inactivated vaccine lacks an effective vaccine adjuvant as an immune activator. The aim of this study was to develop N-2-HACC-Al nano-adjuvant as a high immune-enhancing adjuvant and to make the vaccine suitable for intramuscular and oral administration.</p><p><strong>Methods: </strong>N-2-HACC-Al nano-adjuvant was prepared by ion crosslinking method using the N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC). The N-2-HACC-Al nano-adjuvant was characterised, and its safety was determined by analysing the cytotoxicity and hemolysis. PED inactivated vaccine (N-2-HACC-Al/PEDV) was prepared by electrostatic adsorption method, and mice were inoculated by intramural injection and orally to evaluate the immune enhancement effect and application potential of the N-2-HACC-Al/PEDV.</p><p><strong>Results: </strong>The hemolysis rate was 3.89 ± 0.12% and the activity of PK15 cells was 77.40 ± 1.74%, indicating that the N-2-HACC-Al/PEDV had good biosafety. The levels of PEDV antibodies induced by the N-2-HACC-Al/PEDV were higher than those of commercially available vaccines, both by intramural injection and oral administration. Except for the serum IgG1 levels in the N-2-HACC-Al/PEDV injection group, which were similar to those in the commercial PEDV group, the serum IgG1, IgG2a, IgG2c and sIgA levels in the injection, and the oral groups were significantly higher than those in the commercial group. These results indicated and that N-2-HACC-Al nano-adjuvant significantly enhanced cellular immunity and N-2-HACC-Al nano-adjuvant could deliver PEDV antigen across the mucosal layer of the intestine and induced a strong mucosal immune response.</p><p><strong>Conclusion: </strong>N-2-HACC-Al nano-adjuvant is safe and can efficiently induce humoral, cellular and mucosal immunity efficiently, which provides a new idea for the development of oral mucosal vaccine adjuvant.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1321-1334"},"PeriodicalIF":6.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189042","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":"Ginger-Derived Exosome-Like Nanoparticles Loaded With Indocyanine Green Enhances Phototherapy Efficacy for Breast Cancer.","authors":"Zhaoming Guo, Guqing Li, Lanjun Shen, Jiawei Pan, Danni Dou, Yuwei Gong, Wanwan Shi, Yuhua Sun, Yi Zhang, Kun Ma, Changhao Cui, Wenxin Li, Qiang Liu, Xudong Zhu","doi":"10.2147/IJN.S478435","DOIUrl":"10.2147/IJN.S478435","url":null,"abstract":"<p><strong>Purpose: </strong>Phototherapy has remarkable advantages in cancer treatment, owing to its high efficiency and minimal invasiveness. Indocyanine green (ICG) plays an important role in photo-mediated therapy. However, it has several disadvantages such as poor stability in aqueous solutions, easy aggregation of molecules, and short plasma half-life. This study aimed to develop an efficient nanoplatform to enhance the effects of photo-mediated therapy.</p><p><strong>Methods: </strong>We developed a novel bio-nanoplatform by integrating edible ginger-derived exosome-like nanoparticles (GDNPs) and the photosensitizer, ICG (GDNPs@ICG). GDNPs were isolated from ginger juice and loaded with ICG by co-incubation. The size distribution, zeta potential, morphology, total lipid content, and drug release behavior of the GDNPs@ICG were characterized. The photothermal performance, cellular uptake and distribution, cytotoxicity, anti-tumor effects, and mechanism of action of GDNPs@ICG were investigated both in vitro and in vivo.</p><p><strong>Results: </strong>GDNPs@ICG were taken up by tumor cells via a lipid-dependent pathway. When irradiated by an 808 nm NIR laser, GDNPs@ICG generated high levels of ROS, MDA, and local hyperthermia within the tumor, which caused lipid peroxidation and ER stress, thus enhancing the photo-mediated breast tumor therapy effect. Furthermore, in vivo studies demonstrated that engineered GDNPs@ICG significantly inhibited breast tumor growth and presented limited toxicity. Moreover, by detecting the expression of CD31, N-cadherin, IL-6, IFN-γ, CD8, p16, p21, and p53 in tumor tissues, we found that GDNPs@ICG substantially reduced angiogenesis, inhibited metastasis, activated the anti-tumor immune response, and promoted cell senescence in breast tumor.</p><p><strong>Conclusion: </strong>Our study demonstrated that the novel bio-nanoplatform GDNPs@ICG enhanced the photo-mediated therapeutic effect in breast tumor. GDNPs@ICG could be an alternative for precise and efficient anti-tumor phototherapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1147-1169"},"PeriodicalIF":6.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122782","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":"Human Primary Monocytes as a Model for in vitro Immunotoxicity Testing: Evaluation of the Regulatory Properties of TiO₂ Nanoparticles.","authors":"Tereza Svadlakova, Martina Kolackova, Pavel Kulich, Jan Kotoucek, Michaela Rosecka, Jan Krejsek, Zdeněk Fiala, Ctirad Andrýs","doi":"10.2147/IJN.S498690","DOIUrl":"10.2147/IJN.S498690","url":null,"abstract":"<p><strong>Introduction: </strong>A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO₂) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes.</p><p><strong>Methods: </strong>Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO₂ (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO₂ (co-exposure model), (b) prior activation with TiO₂ alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO₂-treated monocytes into macrophages and their polarization were also assessed.</p><p><strong>Results: </strong>The selected TiO₂ concentration range (30-120 µg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO₂ promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO₂ boosted NLRP3 activity, co-exposure to LPS and TiO₂ inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO₂ on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants.</p><p><strong>Conclusion: </strong>This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1171-1189"},"PeriodicalIF":6.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122796","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":"Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway.","authors":"Qing Song, Aiyuan Zhou, Wei Cheng, Yiyang Zhao, Cong Liu, Yuqin Zeng, Ling Lin, Zijing Zhou, Yating Peng, Ping Chen","doi":"10.2147/IJN.S487097","DOIUrl":"https://doi.org/10.2147/IJN.S487097","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes are rich in a variety of active substances, including microRNA (miR) and have shown powerful therapeutic effects to ameliorate cell injury and diseases. However, the role of BMSCs-derived exosomes on chronic obstructive pulmonary disease (COPD) has been poorly studied. In addition, pulmonary microvascular endothelial cells (PMVECs) apoptosis contributes to the onset of COPD. Inhibition of PMVECs apoptosis can reverse COPD changes. Therefore, the aim of this study was to explore the role of BMSCs-derived exosomes in the apoptosis of PMVECs in COPD and to investigate the potential mechanisms.</p><p><strong>Methods: </strong>We isolated and characterized normal mouse BMSCs-derived exosomes and PMVECs. We performed miR sequencing of BMSCs-derived exosomes. We transfected PMVECs with the miR-30b mimic and Wnt5a overexpression plasmid to assess the underlying mechanisms. Cigarette smoke extract (CSE)-induced COPD mice were treated with exosomes and HBLV-mmu-miR-30b via intratracheal instillation. Finally, we determined the expression of miR-30b and Wnt5a in tissues from patients with COPD.</p><p><strong>Results: </strong>BMSCs-derived exosomes could significantly reduce apoptosis of CSE-induced PMVECs and increase the expression of miR-30b (<i>p</i><0.05). Based on miR sequencing, miR-30b was highly enriched in BMSCs-derived exosomes. The knockdown of miR-30b in BMSCs-derived exosomes could increase the apoptosis of CSE-induced PMVECs (<i>p</i><0.05). miR-30b overexpression significantly reduced apoptosis and repressed Wnt5a protein expression in CSE-induced PMVECs (<i>p</i><0.05). Furthermore, Wnt5a overexpression reversed the anti-apoptotic effect of miR-30b on CSE-induced PMVECs (<i>p</i><0.05). In addition, compared with the COPD group, treatment with BMSCs-derived exosomes and miR-30b overexpression could alleviate emphysema changes, decrease the mean linear intercept and alveolar destructive index, reduce apoptosis, increase the expression of miR-30b, and decrease the expression of Wnt5a in lung tissue (<i>p</i><0.05). Finally, miR-30b expression was decreased in patients with COPD, while Wnt5a expression was increased in these patients (<i>p</i><0.05).</p><p><strong>Conclusion: </strong>BMSCs-derived exosomes could improve the damage of COPD perhaps by delivering miR-30b. miR-30b could reduce apoptosis of CSE-induced PMVECs by targeting Wnt5a.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1191-1211"},"PeriodicalIF":6.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189083","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":"Study on the Mechanism of Black Phosphorus Nanosheets Loading Sr²⁺ Used in Photothermal Antibacterial Treatment.","authors":"Gaoqiang Ma, Binyang Li, Jiayong Diao, Yongzhi Zhang, Bing Zhang, Dongni Wu, Houda Gui, Junhao Zhong, Hongguang Zhu, Dongjiao Zhang","doi":"10.2147/IJN.S495119","DOIUrl":"10.2147/IJN.S495119","url":null,"abstract":"<p><strong>Purpose: </strong>Bacterial infections seriously affect the health of patients and their incidence is very high. Photothermal therapy has shown promising prospects in the treatment of bacterial infections as it can effectively kill bacteria and reduce inflammation. Black phosphorus (BP) is an emerging nanoparticle that can generate heat under the action of near-infrared light, it can safely and effectively kill bacteria through photothermal therapy. In this experiment, black phosphorus was used as a photothermal agent to kill bacteria and strontium ions were loaded onto BP to enhance its stability and antibacterial performance.</p><p><strong>Methods: </strong>BP was obtained by liquid phase exfoliation and Sr²⁺ was loaded onto the surface of BP by electrostatic interaction.</p><p><strong>Results: </strong>BP-Sr was synthesized via electrostatic interactions and characterized using various techniques. The cytocompatibility of BP-Sr was evaluated by CCK8 assay and live/dead staining which showed no significant cytotoxicity with a concentration not exceed 50 μg/mL. Meanwhile, the antibacterial effects showed 99% of bacteria died after 10 min under the action of a 2 W/cm² laser and the structure of bacteria was destroyed. Finally, the transcriptomic results suggest that bacteria death may be related to membrane destruction, metabolic disorders, and transport damage. HE staining and Gram staining also showed that inflammation was significantly alleviated after laser treatment.</p><p><strong>Conclusion: </strong>These findings propose a great solution for bacterial infection and also enrich the theoretical framework supporting the application of BP-Sr in the field of antibiosis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1119-1132"},"PeriodicalIF":6.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079844","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":"Injectable Self-Assembling Procyanidin Nanospheres for Effective Osteoarthritis Treatment.","authors":"Guangjie Li, Fei He, Jianbao Feng, Ge Xu, Chengye Wu, Yufei Qiao, Yang Liu, Hanlin Chen, Pengcheng Du, Jizeng Wang","doi":"10.2147/IJN.S496827","DOIUrl":"10.2147/IJN.S496827","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA), a prevalent joint disease, causes immense suffering to thousands of patients, impairing their mobility and diminishing their quality of life. Current treatment methods primarily rely on analgesics or anti-inflammatory drugs to alleviate symptoms but fail to achieve the desired therapeutic outcome.</p><p><strong>Methods: </strong>To better realize therapeutic effects of OA, procyanidins (PAs), as a type of plant flavonoids with strong antioxidant and anti-inflammatory activities, were designed to self-assembly with well-dispersible Pluronic F127 (PF127) through the hydrogen-bond interaction to present an injectable, biocompatibility PA nanospheres.</p><p><strong>Results: </strong>These nanospheres significantly increased the cell viability in mouse L929 fibroblasts and ADTC5 chondrocytes compared with unassembled PAs. In addition, the self-assembling PAs/PF127 nanospheres enhanced the protein expression of collagen (COL1A1 and COL3A1) in fibroblasts, and the expression of glycosaminoglycan and COL2A1 was also higher than unassembled PAs in chondrocytes, this heralded the potential to achieve OA repair strategies at the cellular level. In an enzymolysis model of rat OA, PAs/PF127 nanospheres significantly reduce joint space swelling in the early stages of cartilage destruction and accelerate the formation of subchondral bone and cartilaginous surface.</p><p><strong>Implication: </strong>This study offers valuable insights into the preparation of novel PA nanospheres for effective repair of OA.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1133-1145"},"PeriodicalIF":6.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079841","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":"In-Situ Electrospinning Dressings Loaded with Kaempferol for Reducing MMP9 to Promote Diabetic Ulcer Healing.","authors":"Jianwen Li, Hongqi Meng, Wenlai Guo, Lubin Zhou, Siyu Wu, Guanghui Gao, Quanzhe Liu, Di You, Wenrui Qu","doi":"10.2147/IJN.S501370","DOIUrl":"10.2147/IJN.S501370","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) are often associated with persistent inflammatory response, impaired macrophage polarization, and slow vascular regeneration. Existing treatments cannot be adapted to wounds and do not achieve the desired therapeutic effects. The high porosity of biomaterials induces more M2 macrophages, while the natural compound kaempferol inhibits the expression of matrix metalloproteinase 9 (MMP9) and thus inhibits the associated inflammatory and immunological responses.</p><p><strong>Methods: </strong>portable electrospinning dressings (PEDs) were prepared from the spinning solution using a portable electrospinning device. The material properties of PEDs were examined by scanning electron microscope, contact angle tester and WVTR-C3. Then, the in vitro biocompatibility of the dressings was evaluated using NIH3T3 cells. The in vivo wound healing efficacy of the dressings was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of epithelization, collagen deposition, MMP9 expression, macrophage polarization, inflammation response and angiogenesis.</p><p><strong>Results: </strong>Material science experiments have shown that the dressing has optimal fiber micromorphology and good water vapor transport properties (WVTR: 4.88 kg m^-2 24h^-1); in vivo, diabetic wound experiments have shown that the high porosity and pharmacological effects of PED4 can mutually promote the rapid healing of diabetic wounds (healed 95.9% on day 15), facilitate the transformation of macrophages from M1-type to M2-type and regulate the expression of MMP9.</p><p><strong>Conclusion: </strong>Portable electrospinning dressings equipped with kaempferol not only better fit irregular wounds, but also promote wound healing through MMP9 and macrophage polarization. Thus, PEDs show great promise for advancing research of personalized diabetic wound healing.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1101-1117"},"PeriodicalIF":6.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079843","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":"T Cell-Derived Apoptotic Extracellular Vesicles Ameliorate Bone Loss via CD39 and CD73-Mediated ATP Hydrolysis.","authors":"Xiaoshan Yang, Yang Zhou, Fuxing Zhou, Lili Bao, Zhengyan Wang, Zihan Li, Feng Ding, Huijuan Kuang, Huan Liu, Shenglong Tan, Xinyuan Qiu, Huan Jing, Shiyu Liu, Dandan Ma","doi":"10.2147/IJN.S491222","DOIUrl":"10.2147/IJN.S491222","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis is a major public health concern characterized by decreased bone density. Among various therapeutic strategies, apoptotic extracellular vesicles (ApoEVs) have emerged as promising agents in tissue regeneration. Specifically, T cell-derived ApoEVs have shown substantial potential in facilitating bone regeneration. However, it remains unclear whether ApoEVs can promote bone mass recovery through enzymatic activity mediated by membrane surface molecules. Therefore, this study aimed to investigate whether T cell-derived ApoEVs could promote bone mass recovery in osteoporosis mice and reveal the underlying mechanisms.</p><p><strong>Methods: </strong>ApoEVs were isolated through sequential centrifugation, and their proteomic profiles were identified via mass spectrometry. Western blot and immunogold staining confirmed the enrichment of CD39 and CD73 on ApoEVs. The role of CD39 and CD73 in hydrolyzing adenosine triphosphate (ATP) to adenosine was evaluated by quantifying the levels of ATP and adenosine. Inhibitors of CD39 and CD73, and an A2BR antagonist were used to explore the molecular mechanism of ApoEVs in promoting bone regeneration.</p><p><strong>Results: </strong>ApoEVs significantly reduced bone loss and promote the osteogenic differentiation of BMMSCs in ovariectomy (OVX) mice. We observed increased levels of extracellular ATP and a decrease in CD39 and CD73, key enzymes in ATP-to-adenosine conversion in bone marrow of OVX mice. We found that ApoEVs are enriched with CD39 and CD73 on their membranes, which enable the hydrolysis of extracellular ATP to adenosine both in vitro and in vivo. The adenosine generated by ApoEVs inhibits the inflammatory response and promotes osteogenesis through A2BR and downstream PKA signaling.</p><p><strong>Conclusion: </strong>T cell-derived ApoEVs are enriched with CD39 and CD73, enabling them to hydrolyze extracellular ATP to adenosine, thereby promoting bone regeneration via A2BR and PKA signaling pathway. Our data underscore the substantive role of T cell-derived ApoEVs to treat osteoporosis, thus providing new ideas for the development of ApoEVs-based therapies in tissue regeneration.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"1083-1100"},"PeriodicalIF":6.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079847","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}