Journal of Nanobiotechnology最新文献

{"title":"MSC-microvesicles protect cartilage from degradation in early rheumatoid arthritis via immunoregulation.","authors":"Shixiong Wei, Rui-Juan Cheng, Sujia Li, Chenyang Lu, Qiuping Zhang, Qiuhong Wu, Xueting Zhao, Xinping Tian, Xiaofeng Zeng, Yi Liu","doi":"10.1186/s12951-024-02922-6","DOIUrl":"10.1186/s12951-024-02922-6","url":null,"abstract":"<p><strong>Objective: </strong>As research into preclinical rheumatoid arthritis (pre-RA) has advanced, a growing body of evidence suggests that abnormalities in RA-affected joint cartilage precede the onset of arthritis. Thus, early prevention and treatment strategies are imperative. In this study, we aimed to explore the protective effects of mesenchymal stem cell (MSC)-derived microvesicles (MVs) on cartilage degradation in a collagen-induced arthritis (CIA) mouse model.</p><p><strong>Methods: </strong>A CIA mouse model was established to observe early pathological changes in cartilage (days 21-25) through histological and radiological examinations. On day 22, MSCs-MVs were intravenously injected into the mice with CIA. Radiological, histological, and flow cytometric examinations were conducted to observe inflammation and cartilage changes in these mice compared to the mice with CIA and the control mice. In vitro, chondrocytes were cultured with inflammatory factors such as IL-1β and TNFα to simulate inflammatory damage to cartilage. After the addition of MVs, changes in inflammatory levels and collagen expression were measured via Western blotting, immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), and quantitative PCR to determine the role of MVs in maintaining chondrocytes.</p><p><strong>Results: </strong>MSC-MVs expressed vesicular membrane proteins (CD63 and Annexin V) and surface markers characteristic of MSCs (CD44, CD73, CD90, and CD105). In the early stages of CIA in mice, a notable decrease in collagen content was observed in the joint cartilage. In mice with CIA, injection of MSCs-MVs resulted in a significant reduction in the peripheral blood levels of IL-1β, TNFα, and IL-6, along with a decrease in the ratio of proinflammatory T and B cells. Additionally, MSC-MVs downregulated the expression of IL-1β, TNFα, MMP-13, and ADAMTS-5 in cartilage while maintaining the stability of type I and type II collagen. These MVs also attenuated the destruction of cartilage, which was evident on imaging. In vitro experiments demonstrated that MSC-MVs effectively suppressed the secretion of the inflammatory factors IL-1β, TNFα, and IL-6 in stimulated peripheral blood mononuclear cells (PBMCs).</p><p><strong>Conclusions: </strong>MSCs-MVs can inhibit the decomposition of the inflammation-induced cartilage matrix by regulating immune cell inflammatory factors to attenuate cartilage destruction. MSC-MVs are promising effective treatments for the early stages of RA.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"673"},"PeriodicalIF":10.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput synthesis and optimization of ionizable lipids through A³ coupling for efficient mRNA delivery.","authors":"Jingjiao Li, Jie Hu, Danni Jin, Haonan Huo, Ning Chen, Jiaqi Lin, Xueguang Lu","doi":"10.1186/s12951-024-02919-1","DOIUrl":"10.1186/s12951-024-02919-1","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency.</p><p><strong>Results: </strong>In this study, we synthesized 623 alkyne-bearing ionizable lipids using the A³ coupling reaction and assessed their effectiveness in mRNA delivery. ILs with specific structural features-18-carbon alkyl chains, a cis-double bond, and ethanolamine head groups-demonstrated superior mRNA delivery capabilities. Variations in saturation, double bond placement, and chain length correlated with decreased efficacy. Alkynes positioned adjacent to nitrogen atoms in ILs reduced the acid dissociation constant (pKa) of LNPs, thereby hindering mRNA delivery efficiency. Conversion of alkynes to alkanes significantly enhanced mRNA delivery of ILs both in vitro and in vivo. Moreover, combining optimized ILs with cKK-E12 yields synergistic LNPs that showed markedly augmented mRNA expression levels in vivo.</p><p><strong>Conclusions: </strong>Overall, our study provides insights into the structure-function relationships of ILs, providing a foundation for the rational design of ILs to enhance the efficacy of LNPs in mRNA delivery.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"672"},"PeriodicalIF":10.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide-based multi-synergistic nanomedicine: an emerging therapeutic for anticancer.","authors":"Yaqin Tang, Qiyu Li, Ziwei Zhou, Huayang Bai, Nianting Xiao, Jing Xie, Chong Li","doi":"10.1186/s12951-024-02929-z","DOIUrl":"10.1186/s12951-024-02929-z","url":null,"abstract":"<p><p>Gas therapy has emerged as a promising approach for treating cancer, with gases like NO, H₂S, and CO showing positive effects. Among these, NO is considered a key gas molecule with significant potential in stopping cancer progression. However, due to its high reactivity and short half-life, delivering NO directly to tumors is crucial for enhancing cancer treatment. NO-driven nanomedicines (NONs) have been developed to effectively deliver NO donors to tumors, showing great progress in recent years. This review provides an overview of the latest advancements in NO-based cancer nanotherapeutics. It discusses the types of NO donors used in current research, the mechanisms of action behind NO therapy for cancer, and the different delivery systems for NO donors in nanotherapeutics. It also explores the potential of combining NO donors with other treatments for enhanced cancer therapy. Finally, it examines the future prospects and challenges of using NONs in clinical settings for cancer treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"674"},"PeriodicalIF":10.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic 3D macroporous MOF oriented urinary exosome metabolomics for early diagnosis of bladder cancer.","authors":"Yiqing Cao, Jianan Feng, Qiao Zhang, Chunhui Deng, Chen Yang, Yan Li","doi":"10.1186/s12951-024-02952-0","DOIUrl":"10.1186/s12951-024-02952-0","url":null,"abstract":"<p><p>Bladder cancer (BCa) exhibits the escalating incidence and mortality due to the untimely and inaccurate early diagnosis. Urinary exosome metabolites, carrying critical tumor cell information and directly related to bladder, emerge as promising non-invasive diagnostic biomarkers of BCa. Herein, the magnetic 3D ordered macroporous zeolitic imidazolate framework-8 (magMZIF-8) is synthesized and used for efficient urinary exosome isolation. Notably, beyond retaining the single crystals and micropores of conventional ZIF-8, MZIF-8 is further enhanced with highly oriented and ordered macropores (150 nm) and the large specific surface area (973 m²·g^-1), which could enable the high purity and yield separation of exosomes via leveraging the combination of size exclusion, affinity, and electrostatic interactions between magMZIF-8 and the surfaces of exosome. Furthermore, the magnetic and hydrophilic properties of magMZIF-8 will further simplify the process and enhance the efficiency of separation. After conditional optimization, a 50 mL of urine is sufficient for exosome metabolomics analysis, and the time for isolating exosomes from 42 urine samples was 2 hours only. Incorporating machine learning algorithms with LC-MS/MS analysis of the metabolic patterns obtained from isolated exosomes, early-stage BCa patients were differentiated from healthy controls, with area under the curve (AUC) value of 0.844-0.9970 in the training set and 0.875-1.00 in the test set, signifying its potential as a reliable diagnostic tool. This study offers a promising approach for the non-invasive and efficient diagnosis of BCa on a large scale via exosome metabolomics.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"671"},"PeriodicalIF":10.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton nanomodulators for enhanced Mn²⁺-mediated chemodynamic therapy of tumors via HCO₃^- regulation.","authors":"Peng Yang, Shaojie Liu, Zhuang Chen, Weijing Liu, Deshang Duan, Zuo Yang, Haohao Yan, Zhiping Rao, Xianghan Zhang, Ruili Zhang, Zhongliang Wang","doi":"10.1186/s12951-024-02843-4","DOIUrl":"10.1186/s12951-024-02843-4","url":null,"abstract":"<p><strong>Background: </strong>Mn²⁺-mediated chemodynamic therapy (CDT) has been emerged as a promising cancer therapeutic modality that relies heavily on HCO₃^- level in the system. Although the physiological buffers (H₂CO₃/HCO₃^-) provide certain amounts of HCO₃^-, the acidity of the tumor microenvironment (TME) would seriously affect the HCO₃^- ionic equilibrium (H₂CO₃ ⇌ H⁺ + HCO₃^-). As a result, HCO₃^- level in the tumor region is actually insufficient to support effective Mn²⁺-mediated CDT.</p><p><strong>Results: </strong>In this study, a robust nanomodulator MnFe₂O₄@ZIF-8 (PrSMZ) with the capability of in situ self-regulation HCO₃^- is presented to enhance therapeutic efficacy of Mn²⁺-mediated CDT. Under an acidic tumor microenvironment, PrSMZ could act as a proton sponge to shift the HCO₃^- ionic equilibrium to the positive direction, significantly boosting the generation of the HCO₃^-. Most importantly, such HCO₃^- supply capacity of PrSMZ could be finely modulated by its ZIF-8 shell thickness, resulting in a 1000-fold increase in reactive oxygen species (ROS) generation. Enhanced ROS-dependent CDT efficacy is further amplified by a glutathione (GSH)-depletion ability and the photothermal effect inherited from the inner core MnFe₂O₄ of PrSMZ to exert the remarkable antitumor effect on mouse models.</p><p><strong>Conclusions: </strong>This work addresses the challenge of insufficient HCO₃^- in the TME for Mn²⁺-mediated Fenton catalysts and could provide a promising strategy for designing high-performance Mn²⁺-mediated CDT agents to treat cancer effectively.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"670"},"PeriodicalIF":10.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal nanoparticle delivery and cellular response: a review of the bidirectional nanoparticle-cell interplay in mucosa based on physiochemical properties.","authors":"Yu Wang, Yilei Mo, Yingwei Sun, Jing Li, Yu An, Nianping Feng, Ying Liu","doi":"10.1186/s12951-024-02930-6","DOIUrl":"10.1186/s12951-024-02930-6","url":null,"abstract":"<p><p>Orally administered nanocarriers play an important role in improving druggability, promoting intestinal absorption, and enhancing therapeutic applications for the treatment of local and systemic diseases. However, the delivering efficiency and cell response in mucosa to orally administered nanocarriers is affected by the physiological environment and barriers in the gastrointestinal tract, the physicochemical properties of the nanocarriers, and their bidirectional interactions. Goblet cells secrete and form extracellular mucus, which hinders the movement of nanoparticles. Meanwhile, intestinal epithelial cells may absorb the NPs, allowing for their transcytosis or degradation. Conversely, nanoparticle-induced toxicity may occur as a biological response to the nanoparticle exposure. Additionally, immune response and cell functions in secretions such as mucin, peptide, and cytokines may also be altered. In this review, we discuss the bidirectional interactions between nanoparticles and cells focusing on enterocytes and goblet cells, M cells, and immune cells in the mucosa according to the essential role of intestinal epithelial cells and their crosstalk with immune cells. Furthermore, we discuss the recent advances of how the physiochemical properties of nanoparticles influence their interplay, delivery, and fate in intestinal mucosa. Understanding the fate of nanoparticles with different physiochemical properties from the perspective of their interaction with cells in mucosa provides essential support for the development, rational design, potency maximation, and application of advanced oral nanocarrier delivery systems.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"669"},"PeriodicalIF":10.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembly antimicrobial peptide for treatment of multidrug-resistant bacterial infection.","authors":"Xuanxuan Ma, Na Yang, Ruoyu Mao, Ya Hao, Yuanyuan Li, Ying Guo, Da Teng, Yinhua Huang, Jianhua Wang","doi":"10.1186/s12951-024-02896-5","DOIUrl":"10.1186/s12951-024-02896-5","url":null,"abstract":"<p><p>The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72-57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G⁺) and gram-negative (G^-) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"668"},"PeriodicalIF":10.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Losartan-based nanocomposite hydrogel overcomes chemo-immunotherapy resistance by remodeling tumor mechanical microenvironment.","authors":"Xiaodong Hou, Yuting Shen, Bin Huang, Qiuyan Li, Shaoyue Li, Tingting Jiang, Xuexia Shan, Weichen Xu, Shuo Liu, Shengbo Wu, De Zhao, Anqi Zhu, Liping Sun, Huixiong Xu, Wenwen Yue","doi":"10.1186/s12951-024-02871-0","DOIUrl":"10.1186/s12951-024-02871-0","url":null,"abstract":"<p><p>Preclinical studies demonstrating high cure rates with PD1/PD-L1 combinations have led to numerous clinical trials, but emerging results are disappointing. These combined immunotherapies are commonly employed for patients with refractory tumors following prior treatment with cytotoxic agents. Here, we uncovered that the post-chemotherapy tumor presents a unique mechanical microenvironment characterized by an altered extracellular matrix (ECM) elasticity and increased stiffness, which facilitate the development of aggressive tumor phenotypes and confer resistance to checkpoint blocking therapy. As thus, we rationally designed an in situ nanocomposite hydrogel system, LOS&FeOX@Gel, which enabled effective and specific delivery of the therapeutic payloads (losartan [LOS] and oxaliplatin [OX]) into tumor. We demonstrate that sustained release of LOS effectively remodels the tumor mechanical microenvironment (TMM) by reducing ECM deposition and its associated \"solid stress\", thereby augmenting the efficacy of OX and its immunological effects. Importantly, this hydrogel system greatly sensitized post-chemotherapy tumor to checkpoint blocking therapy, showing synergistic therapeutic effects against cancer metastasis. Our study provides mechanistic insights and preclinical rationale for modulating TMM as a potential neoadjuvant regimen for tumor to optimize the benefits of chemo-immunotherapy, which lays the groundwork for leveraging \"mechanical-immunoengineering\" strategies to combat refractory tumors.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"667"},"PeriodicalIF":10.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p.","authors":"Tianyu Wu, Wenwu Zhu, Rui Duan, Jianfei Sun, Siyuan Bao, Kaiyan Chen, Bing Han, Yuqiong Chen, Yao Lu","doi":"10.1186/s12951-024-02928-0","DOIUrl":"10.1186/s12951-024-02928-0","url":null,"abstract":"<p><strong>Background: </strong>Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48-72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms.</p><p><strong>Results: </strong>mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb).</p><p><strong>Conclusions: </strong>In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"666"},"PeriodicalIF":10.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage membrane-functionalized manganese dioxide nanomedicine for synergistic treatment of atherosclerosis by mitigating inflammatory storms and promoting cholesterol efflux.","authors":"Sijin Chen, Wenli Zhang, Chun Tang, Xiyue Rong, Yun Liu, Ying Luo, Lian Xu, Zhongsheng Xu, Junrui Wang, Yi Wang, Qianying Du, Bo Liu, Yu Zhang, Jia Liu, Dajing Guo","doi":"10.1186/s12951-024-02939-x","DOIUrl":"10.1186/s12951-024-02939-x","url":null,"abstract":"<p><p>Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO₂-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO₂-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE^-/- mouse model, Col@HMnO₂-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"22 1","pages":"664"},"PeriodicalIF":10.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}