{"title":"Bioactive Porous Composite Implant Guides Mesenchymal Stem Cell Differentiation and Migration to Accelerate Bone Reconstruction.","authors":"Sheng Wang, Demeng Xia, Wenxue Dou, Aimin Chen, Shuogui Xu","doi":"10.2147/IJN.S479893","DOIUrl":"10.2147/IJN.S479893","url":null,"abstract":"<p><strong>Background: </strong>Delayed healing and non-healing of bone defects pose significant challenges in clinical practice, with metal materials increasingly recognized for their significance in addressing these issues. Among these materials, Strontium (Sr) and Zinc (Zn) have emerged as promising agents for promoting bone repair. Building upon this insight, this research evaluates the impact of a porous Sr@Zn@SiO<sub>2</sub> nanocomposite implant on bone regeneration, aiming to advance the field of bone repair.</p><p><strong>Methods: </strong>The preparation of the Sr@Zn@SiO<sub>2</sub> composite implant involves various techniques such as roasting, centrifugation, and washing. The material's composition is examined, and its microstructure and element distribution are analyzed using TEM and elemental scanning technology. In vitro experiments entail the isolation and characterization of BMSCs followed by safety assessments of the implant material, evaluation of cell migration capabilities, and relevant proliferation markers. Mechanistically, this study delves into key targets associated with significant changes in the osteogenic process. In vivo experiments involve establishing a rat femur bone defect model, followed by assessment of the osteogenic potential of Sr@Zn@SiO<sub>2</sub> using Micro-CT imaging and tissue section staining.</p><p><strong>Results: </strong>Through in vivo and in vitro investigations, we validate the osteogenic efficacy of the Sr@Zn@SiO<sub>2</sub> composite implant. In vitro analyses demonstrate that porous Sr@Zn@SiO<sub>2</sub> nanocomposite materials upregulate BMP-2 expression, leading to the activation of Smad1/5/9 phosphorylation and subsequent activation of downstream osteogenic genes, culminating in BMSCs osteogenic differentiation and bone proliferation. And the migration of BMSCs is closely related to the high expression of CXCL12/CXCR4, which will also provide the conditions for osteogenesis. In vivo, the osteogenic ability of Sr@Zn@SiO<sub>2</sub> was also confirmed in rats.</p><p><strong>Conclusion: </strong>In our research, the porous Sr@Zn@SiO<sub>2</sub> composite implant displays prominent osteogenic effect and promotes the migration and differentiation of BMSCs to promote bone defect healing. This bioactive implant has surgical application potential in the future.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12111-12127"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710113","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}
Moyan Zhao, Zixuan Zhou, Amir Sherchan, Weizhong Yuan, Xiaoyun Xie, Maoquan Li
{"title":"An Innovative Delivery System of Oxygen-Releasing Nanospheres and Self-Healing Hydrogels Enhances the Therapeutic Effectiveness of Bone Marrow Mesenchymal Stem Cells for Chronic Limb-Threatening Ischemia.","authors":"Moyan Zhao, Zixuan Zhou, Amir Sherchan, Weizhong Yuan, Xiaoyun Xie, Maoquan Li","doi":"10.2147/IJN.S483541","DOIUrl":"10.2147/IJN.S483541","url":null,"abstract":"<p><strong>Purpose: </strong>Bone marrow mesenchymal stem cells (BMSCs) have emerged as promising candidate for postoperative therapeutics in chronic limb-threatening ischemia (CLTI). Nevertheless, their effectiveness is limited by their low survival rate and impaired functionality in the ischemic microenvironment. To overcome these challenges, we have devised an innovative delivery approach to support the utilization of BMSCs in CLTI therapy.</p><p><strong>Methods: </strong>We synthesized oxygen-releasing nanospheres and self-healing hydrogels. The in vivo functionality of the hydrogel-nanosphere delivery system was evaluated via a multimodality animal live imaging system. A unilateral lower limb ischemia model was established in mice, and a delivery system loaded with BMSCs was administered. The experimental groups included normal mice, ischemic mice, ischemic mice treated with BMSCs in PBS, and ischemic mice treated with BMSCs in the delivery system. Blood perfusion was quantitatively measured via a laser doppler flowmeter (LDF). Immunofluorescence, Masson's trichrome staining, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were also used.</p><p><strong>Results: </strong>For cell viability analysis 80 μg.mL<sup>-1</sup> was considered the optimal concentration for cell survival. In vivo, 18 days after injection, the cell membrane fluorescence signal in the delivery system was significantly greater (5.655<sup>10</sup>±8.226<sup>8</sup>) p/s/cm²/sr than that in the other groups (p=0.043). Ischemic mice treated with BMSCs in the delivery system presented an improved limb salvage rate (0.926±0.12)% compared with that of ischemic mice treated with BMSCs in PBS (0.841±0.029)% at the 5th week after ischemia establishment (p=0.0033).</p><p><strong>Conclusion: </strong>Our findings suggest that the survival time of BMSCs is prolonged in this innovative delivery system. The combination of nanospheres and hydrogels effectively restored vascular blood perfusion while exerting minimal toxicity on BMSCs. This novel approach combining oxygen-releasing nanospheres and self-healing hydrogels as a delivery system represents an advancement in enhancing the functionality of BMSCs to treat CLTI.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12153-12170"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715829","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}
Pilong Shi, Yuetong Sha, Xinran Wang, Tao Yang, Jiawei Wu, Jiajun Zhou, Kai Liu, Xue Guan, Song Wang, Yongsheng Liu, Jingquan Gao, Hongli Sun, Tao Ban, Yonggang Cao
{"title":"Targeted Delivery and ROS-Responsive Release of Lutein Nanoassemblies Inhibit Myocardial Ischemia-Reperfusion Injury by Improving Mitochondrial Function.","authors":"Pilong Shi, Yuetong Sha, Xinran Wang, Tao Yang, Jiawei Wu, Jiajun Zhou, Kai Liu, Xue Guan, Song Wang, Yongsheng Liu, Jingquan Gao, Hongli Sun, Tao Ban, Yonggang Cao","doi":"10.2147/IJN.S488532","DOIUrl":"10.2147/IJN.S488532","url":null,"abstract":"<p><strong>Purpose: </strong>Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.</p><p><strong>Methods: </strong>In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.</p><p><strong>Results: </strong>Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.</p><p><strong>Conclusion: </strong>Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11973-11996"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710152","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":"Curcumin-Loaded Long-Circulation Liposomes Ameliorate Insulin Resistance in Type 2 Diabetic Mice.","authors":"Kang-Xin Li, Hui Yuan, Jing Zhang, Xiao-Bin Peng, Wei-Fen Zhuang, Wen-Tao Huang, Hui-Xin Liang, Ying Lin, Ying-Zhen Huang, Shu-Lan Qin","doi":"10.2147/IJN.S487519","DOIUrl":"10.2147/IJN.S487519","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.</p><p><strong>Methods: </strong>CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.</p><p><strong>Results: </strong>CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (-33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.</p><p><strong>Conclusion: </strong>CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12099-12110"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710120","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":"Synergistic Fat-Reducing Effect of Deoxycholic Acid and Rhein in Lipid-Based Nanoparticles with Reduced Toxicity for Obesity Treatment.","authors":"Ching-Yun Hsu, Tse-Hung Huang, Zih-Chan Lin, Chih-Jung Chen, Erica Hwang, Wei-Jhang Chen, Jia-You Fang","doi":"10.2147/IJN.S494416","DOIUrl":"10.2147/IJN.S494416","url":null,"abstract":"<p><strong>Purpose: </strong>Injectable deoxycholic acid (DA) has been approved for removing excess submental fat and is off-label for local adipose tissue reduction. Conventional DA injections fail to control fat reduction and generate severe adverse effects in adjacent non-adipose tissues. We designed squarticles as lipid-based nanoparticles for DA delivery to reduce fat accumulation.</p><p><strong>Methods: </strong>The liquid lipid phase of the squarticles was composed of squalene, which was previously reported to sequester the toxicity of overdosed drugs. Rhein, a natural anti-adipogenic compound, was incorporated into the squarticles for combined fat-lowering.</p><p><strong>Results: </strong>The squarticles had an average diameter of 93 nm and high rhein encapsulation (96%). The nanoparticles were easily internalized into mature adipocytes and were located in the lysosomes. DA induces adipocyte death via apoptosis and necrosis; however, nanoencapsulation can decrease cell death. Compared to free DA, squarticles showed superior mitigation of cytotoxicity against non-targeted cells (skin fibroblasts). Oil Red O staining indicated that squarticles loaded with DA or rhein alone inhibited lipid droplets by 42% and 17%, respectively. DA and rhein worked together in squarticles to further suppress fat accumulation by 50%. Dual administration of DA and rhein to the nanocarriers downregulated adipokines. The intraperitoneal administration of squarticles loaded with DA and rhein significantly decreased body weight, total cholesterol, and adipokine release. Histological analysis revealed that squarticles reduced adipocyte hypertrophy in the groin and epididymis by 11% and 53%, respectively. We examined the toxicity of the combination of DA+rhein in healthy rats that received a dose three-fold higher than that used in the pharmacological assessment. The survival rate of the overdosed DA+rhein increased from 50% to 100% after nanoencapsulation. Free compounds induce ascites, liver size reduction, AST/ALT elevation (1.5-fold), and potassium imbalance in rats. Nanoencapsulation significantly reduced these adverse effects.</p><p><strong>Conclusion: </strong>Our findings highlight the potential of squarticles for treating obesity.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12129-12151"},"PeriodicalIF":6.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710066","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":"Amphiphilic Janus Nanoparticles for Effective Treatment of Bacterial Pneumonia by Attenuating Inflammation and Targeted Bactericidal Capability.","authors":"Xiangjun Chen, Weiwei Li, Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong","doi":"10.2147/IJN.S486450","DOIUrl":"10.2147/IJN.S486450","url":null,"abstract":"<p><strong>Introduction: </strong><i>Pseudomonas aeruginosa (P. aeruginosa)</i>-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of <i>P. aeruginosa</i> infection to multiple medications.</p><p><strong>Purpose: </strong>In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic <i>P. aeruginosa</i>.</p><p><strong>Results: </strong>As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating <i>P. aeruginosa</i> strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.</p><p><strong>Discussion: </strong>In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12039-12051"},"PeriodicalIF":6.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710129","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":"Extracellular Vesicles Derived from Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cells Ameliorate Inflammatory Responses in Experimental Colitis via the PI3K/AKT Signaling Pathway.","authors":"Shuai Tang, Wenyu Feng, Zekun Li, Xinjuan Liu, Tong Yang, Fulan Wei, Gang Ding","doi":"10.2147/IJN.S494321","DOIUrl":"10.2147/IJN.S494321","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.</p><p><strong>Methods: </strong>A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.</p><p><strong>Results: </strong>The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11997-12013"},"PeriodicalIF":6.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710139","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}
Kaiqiang Li, Jing Jin, Yimin Yang, Xuling Luo, Yaling Wang, Aibo Xu, Ke Hao, Zhen Wang
{"title":"Application of Nanoparticles for Immunotherapy of Allergic Rhinitis.","authors":"Kaiqiang Li, Jing Jin, Yimin Yang, Xuling Luo, Yaling Wang, Aibo Xu, Ke Hao, Zhen Wang","doi":"10.2147/IJN.S484327","DOIUrl":"10.2147/IJN.S484327","url":null,"abstract":"<p><p>Allergen Immunotherapy (AIT) is the only etiological therapeutic method available for allergic rhinitis (AR). Currently, several options for AIT in the market, such as subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), have different routes of administration. These traditional methods have achieved encouraging outcomes in clinic. However, the side effects associated with these methods have raised the need for innovative approaches for AIT that improve safety, shorten the course of treatment and increase local drug concentration. Nanoparticles (NPs) are particles ranging in size from 1 to 100 nm, which have been hired as potential adjuvants for AIT. NPs can be employed as agents for modulating immune responses in AR or/and carriers for loading proteins, peptides or DNA molecules. This review focuses on different kinds of nanoparticle delivery systems, including chitosan nanoparticles, exosomes, metal nanoparticles, and viral nanoparticles. We summarized the advantages and limitations of NPs for the treatment of allergic rhinitis. Overall, NPs are expected to be a therapeutic option for AR, which requires more in-depth studies and long-term therapeutic validation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"12015-12037"},"PeriodicalIF":6.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710133","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":"Prospective Application of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Disseminated Intravascular Coagulation.","authors":"Chengran Wang, Xiaoqing Zhao, Keyan Wang, Huixin Liang, Shuhan Chen, Yajie Liu, Hua Yao, Jinlan Jiang","doi":"10.2147/IJN.S467158","DOIUrl":"10.2147/IJN.S467158","url":null,"abstract":"<p><p>Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11957-11971"},"PeriodicalIF":6.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681548","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":"Augment of Ferroptosis with Photothermal Enhanced Fenton Reaction and Glutathione Inhibition for Tumor Synergistic Nano-Catalytic Therapy.","authors":"Qingcheng Song, Yiran Zhang, Hongzhi Hu, Xuemei Yang, Xin Xing, Jianhua Wu, Yanbin Zhu, Yingze Zhang","doi":"10.2147/IJN.S480586","DOIUrl":"10.2147/IJN.S480586","url":null,"abstract":"<p><strong>Introduction: </strong>Ferroptosis-driven tumor ablation strategies based on nanotechnology could be achieved by elevating intracellular iron levels or inhibiting glutathione peroxidase 4 (GPX4) activity. However, the intracellular antioxidative defense mechanisms endow tumor cells with ferroptosis resistance capacity. The purpose of this study was to develop a synergistic therapeutic platform to enhance the efficacy of ferroptosis-based tumor therapy.</p><p><strong>Methods: </strong>In this study, a multifunctional nano-catalytic therapeutic platform (mFeB@PDA-FA) based on chemodynamic therapy (CDT) and photothermal therapy (PTT) was developed to effectively trigger ferroptosis in tumor. In our work, iron-based mesoporous Fe<sub>3</sub>O<sub>4</sub> nanoparticles (mFe<sub>3</sub>O<sub>4</sub> NPs) were employed for the encapsulation of L-buthionine sulfoximine (BSO), followed by the modification of folic acid-functionalized polydopamine (PDA) coating on the periphery. Then, the antitumor effect of mFeB@PDA-FA NPs was evaluated using Human OS cells (MNNG/HOS) and a subcutaneous xenograft model of osteosarcoma.</p><p><strong>Results: </strong>mFe<sub>3</sub>O<sub>4</sub> harboring multivalent elements (Fe<sup>2+/3+</sup>) could catalyze hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into highly cytotoxic ˙OH, while the tumor microenvironment (TME)-responsive released BSO molecules inhibit the biosynthesis of GSH, thus achieving the deactivation of GPX4 and the enhancement of ferroptosis. Moreover, thanks to the remarkable photothermal conversion performance of mFe<sub>3</sub>O<sub>4</sub> and PDA shell, PTT further synergistically enhanced the efficacy of CDT and facilitated ferroptosis. Both in vivo and in vitro experiments confirmed that this synergistic therapy could achieve excellent tumor inhibition effects.</p><p><strong>Conclusion: </strong>The nanotherapeutic platform mFeB@PDA-FA could effectively disrupted the redox homeostasis in tumor cells for boosting ferroptosis through the combination of CDT, PTT and GSH elimination, which provided a new perspective for the treatment of ferroptosis sensitive tumors.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11923-11940"},"PeriodicalIF":6.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686915","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}