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Chitosan-based drug delivery system targeting the myocardial microenvironment: Delivery strategy and mechanism exploration for precise treatment of myocardial injury 基于壳聚糖的靶向心肌微环境给药系统:精准治疗心肌损伤的给药策略及机制探索
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-21 DOI: 10.1016/j.nano.2025.102868
YuanYuan Zuo , Yanyan Zhu , Xuying Ding , Leiyi Wang , Jiaxin Zheng , Qucheng Huang , Hewei Xu , Chang Liu
Myocardial injury (MI) is the primary pathogenic process in many cardiovascular disorders. And inadequate medication targeting, unregulated release, and severe side effects are major issues in treatment. Recently, chitosan-based nano-delivery systems have gained popularity in the precision treatment of cardiovascular diseases due to their high biocompatibility, biodegradability, and ease of chemical modification. These devices can be functionally tuned to respond to the cardiac microenvironment, resulting in tailored drug enrichment and sustained release. In this paper, we provide a systematic assessment of the progress of chitosan and its derivatives in MI treatments, including material design approach, environmental response mechanism, drug loading and release management, and mode of action. It also examines the limitations of clinical translation and predicts future development directions. The study shows that chitosan-based nanosystems have significant potential in regulating inflammation and anti-oxidative stress, as well as promoting vascular neovascularization and myocardial repair.
心肌损伤是许多心血管疾病的主要致病过程。治疗中的主要问题是药物靶向不充分、药物释放不规范以及严重的副作用。近年来,基于壳聚糖的纳米递送系统因其高生物相容性、可生物降解性和易于化学修饰而在心血管疾病的精确治疗中得到了广泛的应用。这些装置可以在功能上调整以响应心脏微环境,从而产生量身定制的药物富集和持续释放。本文综述了壳聚糖及其衍生物在心肌梗死治疗中的研究进展,包括材料设计方法、环境反应机制、药物加载与释放管理、作用方式等。探讨了临床翻译的局限性,并预测了未来的发展方向。研究表明,壳聚糖纳米系统在调节炎症和抗氧化应激、促进血管新生和心肌修复方面具有重要的潜力。
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引用次数: 0
Nanotechnology-based delivery strategies for drugs and vaccines targeting blood stage malaria: A systematic review 针对血期疟疾的基于纳米技术的药物和疫苗递送策略:系统综述。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-13 DOI: 10.1016/j.nano.2025.102869
Yohana Amos , Clarence Rubaka , Elingarami Sauli , Hulda Swai , Anneth Tumbo
The blood stage of malaria, where Plasmodium parasites invade red blood cells, accounts for most clinical symptoms and severe complications. However, current drugs and vaccines remain limited by drug resistance, toxicity, poor stability, and reduced overall efficacy. This review aimed to synthesize evidence on nanotechnology-based delivery systems for improving targeting specificity, enhancing drug and antigen stability, and optimizing therapeutic outcomes. Forty (40) studies from 2005 to 2025 were systematically analyzed, focusing on lipid, polymeric, inorganic, and protein-based nanoparticles targeting the blood stage. Results showed that functionalized nanocarriers with ligands targeting infected red blood cells significantly enhanced drug efficacy and reduced systemic toxicity. In vaccine development, nanoparticles used as antigen carriers elicited strong immune responses, achieving up to 83.3 % survival in in vivo preclinical models. Despite these promising outcomes, challenges such as scalable production, clinical translation, and regulatory approval persist. Overall, the findings highlight nanomedicine's transformative potential for malaria treatment and prevention.
疟疾的血液阶段,疟原虫侵入红细胞,是大多数临床症状和严重并发症的原因。然而,目前的药物和疫苗仍然受到耐药性、毒性、稳定性差和总体疗效降低的限制。本文综述了基于纳米技术的递送系统在提高靶向特异性、增强药物和抗原稳定性以及优化治疗结果方面的研究进展。从2005年到2025年,我们系统地分析了40项研究,重点是针对血液阶段的脂质、聚合物、无机和蛋白质纳米颗粒。结果表明,功能化纳米载体与配体靶向感染红细胞显著提高药物疗效和降低全身毒性。在疫苗开发中,用作抗原载体的纳米颗粒引发了强烈的免疫反应,在体内临床前模型中实现了高达83.3 %的存活率。尽管取得了这些有希望的成果,但诸如可扩展生产、临床转化和监管批准等挑战仍然存在。总的来说,这些发现突出了纳米医学在疟疾治疗和预防方面的变革潜力。
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引用次数: 0
Zebrafish as a model for assessing the nanotechnology-based approaches in cancer diagnosis, therapy and theranostic: A historical review, trends and challenges 斑马鱼作为评估基于纳米技术的癌症诊断、治疗和治疗方法的模型:历史回顾、趋势和挑战。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-10 DOI: 10.1016/j.nano.2025.102867
Jaqueline Cardoso Jacintho , Ana Clara Nogueira Ferreira , Thiago Lopes Rocha
Nanotechnology-based approaches (NBA) can improve tumor diagnosis and treatment. Thus, zebrafish (Danio rerio) emerge as a model system to investigate antitumoral effects, biodistribution and mechanism of action of nanomaterials (NMs). The current study aimed to summarize and critically analyze the literature concerning the use of zebrafish as an in vivo model for assessing the NBA in diagnosis, therapy and theranostics of cancer. Revised data (n = 95) showed an increasing number of publications in recent years. The main study approach was therapeutic (83.16 %), while diagnosis and theranostics represented 9.47 % and 7.37 %, respectively. 95.8 % used the embryo-larval stage of zebrafish. The most studied NM was the nanoparticles (NPs). Breast cancer, liver and melanoma were the tumors most studied. Overall, NMs can reduce chemotherapeutic drug toxicity, inhibit tumor growth, metastasis and angiogenesis, also promote tumor imaging and tracking. Zebrafish is a suitable emerging model system in cancer nanomedicine research.
基于纳米技术的方法(NBA)可以改善肿瘤的诊断和治疗。因此,斑马鱼(Danio rerio)成为研究纳米材料(NMs)的抗肿瘤作用、生物分布和作用机制的模型系统。本研究旨在总结和批判性分析有关使用斑马鱼作为体内模型来评估NBA在癌症诊断、治疗和治疗中的作用的文献。订正数据(n = 95)显示近年来出版物的数量不断增加。研究方法以治疗为主(83.16% %),诊断和治疗分别占9.47 %和7.37 %。95.8% 采用斑马鱼胚胎幼虫期。研究最多的纳米是纳米颗粒(NPs)。乳腺癌、肝癌和黑色素瘤是研究最多的肿瘤。总体而言,NMs可以降低化疗药物毒性,抑制肿瘤生长、转移和血管生成,促进肿瘤成像和跟踪。斑马鱼是肿瘤纳米医学研究中一种合适的新兴模型系统。
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引用次数: 0
Schisandrin-loaded β-cyclodextrin nanoparticles for atherosclerosis therapy 五味子载β-环糊精纳米颗粒用于动脉粥样硬化治疗。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-10 DOI: 10.1016/j.nano.2025.102866
Qiuxia Huang, Xinyao Liu, Jinjin Yu, Xinya Zhang, Siqi Wang, Lili Zhou, Xiaofeng Niu, Weifeng Li
Nanoparticle delivery systems have been extensively investigated as novel therapeutic strategies to promote drug-resistant disease. These nanoparticle formulations demonstrated improved bioavailability and enhanced tissue targeting. Also, there is growing acceptance of the value of traditional Chinese medicine in fighting disease. In this study, combining the advantages of nanomedicine with the characteristics of the acidic inflammatory microenvironment of atherosclerosis, a nanoplasmonic platform encapsulating the unstable drug Sch was designed for the treatment of atherosclerotic lesions. pH-responsive nanocarriers, an acid-labile material of acetylated β-cyclodextrin (β-CD) (Ac-bCD) were synthesized by chemical modification of β-CD. The resulting nanoparticles loaded with Sch (Sch-NPs) were prepared using a solvent evaporation method. In ApoE−/− mice fed a high-fat diet, Sch-NPs alleviated arterial damage, inhibited lipid metabolism disorders, reduced plaque area, and promoted plaque stability. In addition, Sch-NPs effectively reduced inflammatory infiltration and oxidative stress by modulating the MAPK pathway. Our findings demonstrate the promising applications of pH-responsive nanoparticles loaded with Sch for enhanced disease therapies such as atherosclerosis.
纳米颗粒递送系统作为促进耐药疾病的新治疗策略已被广泛研究。这些纳米颗粒制剂显示出更好的生物利用度和增强的组织靶向性。此外,越来越多的人接受了中医在对抗疾病方面的价值。本研究结合纳米医学的优势和动脉粥样硬化酸性炎症微环境的特点,设计了包封不稳定药物Sch的纳米等离子体平台,用于动脉粥样硬化病变的治疗。以乙酰化β-环糊精(β-CD) (Ac-bCD)为原料,对β-CD进行化学修饰,合成了ph响应型纳米载体。采用溶剂蒸发法制备了Sch- nps纳米粒子。在喂食高脂肪饮食的ApoE-/-小鼠中,Sch-NPs减轻动脉损伤,抑制脂质代谢紊乱,减少斑块面积,促进斑块稳定性。此外,Sch-NPs通过调节MAPK通路有效减少炎症浸润和氧化应激。我们的研究结果表明,负载Sch的ph响应纳米颗粒在增强疾病治疗(如动脉粥样硬化)方面具有很好的应用前景。
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引用次数: 0
Therapeutic potential and toxicological challenges of metal nanoparticles in drug delivery: A comprehensive review 金属纳米颗粒在药物传递中的治疗潜力和毒理学挑战:综合综述。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-09 DOI: 10.1016/j.nano.2025.102862
Sajid Mehmood , Sajiya Iraqui , Rajesh Kumar Ojha , Nisha Sharma , Ab Rahman Marlinda
Metal nanoparticles (NPs) have emerged as advanced drug delivery systems, combining high therapeutic potential with complex safety considerations. Their unique physicochemical features, including high surface-to-volume ratios, tunable surfaces, and the ability to cross biological barriers, enable applications in targeted drug delivery and theranostics. Gold (Au), silver (Ag), iron oxide (Fe₃O₄), zinc oxide (ZnO), and platinum (Pt) NPs demonstrate outstanding efficacy: AuNPs achieve >90 % drug loading and 3–5× improved tumour targeting, AgNPs show up to 99 % antimicrobial activity, and Fe₃O₄ NPs function as both drug carriers and MRI contrast agents. However, toxicity remains a major hurdle. Reported challenges include dose-dependent cytotoxicity (IC₅₀: 10–40 μg/mL), hepatic retention (30–40 %), oxidative stress (2–10× ROS increase), and immune activation (up to 3-fold cytokine elevation). Safety is governed by physicochemical properties, with <10 nm NPs showing efficient penetration but higher genotoxicity, and cationic surfaces being 2–3× more cytotoxic. Several strategies have been developed to overcome these barriers. PEGylation reduces macrophage uptake by 60–75 % and extends circulation time, biodegradable hybrids reduce long-term accumulation by 70–80 %, and controlled-release systems cut doses by 30–50 % without compromising efficacy. Advances in computational tools, such as machine learning (~87 % predictive accuracy), along with standardized testing (<20 % variability), have accelerated preclinical evaluation by 40–50 %. These improvements contribute to therapeutic indices >10 and Phase I trial success rates of 65–75 %, significantly outperforming first-generation nanocarriers. This review highlights the need for multidisciplinary integration of nanotechnology, toxicology, computational modelling, and regulatory frameworks. With continued innovation, metal NPs hold the potential to revolutionize precision medicine through safer, scalable, and clinically translatable nanoplatforms.
金属纳米颗粒(NPs)已成为先进的药物输送系统,结合了高治疗潜力和复杂的安全性考虑。它们独特的物理化学特性,包括高表面体积比、可调表面和跨越生物屏障的能力,使其在靶向药物输送和治疗方面的应用成为可能。金(Au),银(Ag),氧化铁(Fe₃O₄),氧化锌(ZnO)和铂(Pt) NPs表现出出色的功效:AuNPs达到bbb90 %的药物负载和3-5倍的肿瘤靶向性,AgNPs显示出高达99 %的抗菌活性,Fe₃O₄NPs既可以作为药物载体又可以作为MRI造影剂。然而,毒性仍然是一个主要障碍。报告的挑战包括剂量依赖性细胞毒性(IC₅₀:10-40 μg/mL),肝潴留(30-40 %),氧化应激(2-10倍ROS增加)和免疫激活(高达3倍的细胞因子升高)。安全性由理化性质决定,10期和I期试验的成功率为65- 75% %,明显优于第一代纳米载体。这篇综述强调了纳米技术、毒理学、计算模型和监管框架的多学科整合的必要性。随着不断的创新,金属纳米粒子通过更安全、可扩展和临床可翻译的纳米平台,有望彻底改变精准医疗。
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引用次数: 0
Inhibition of growth of the human chronic leukemia cancer cell line K562 using capsaicin-containing nanofibers: an in vitro study 含辣椒素纳米纤维抑制人慢性白血病K562细胞生长的体外研究
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-03 DOI: 10.1016/j.nano.2025.102864
Mohadeseh Heidarzadeh , Habib Hamidinezhad , Fatemeh Hedayati Tabari , Mohammad Karimian
This study aims to investigate the anticancer properties of capsaicin, the active substance of red pepper, in different concentrations (2 %, 6 %, and 10 %) by chitosan and polyvinyl alcohol nanofiber substrate, against the K562 leukemia cell line. For this purpose, chitosan (Cs) and polyvinyl alcohol (PVA) polymers were used to produce nanofibers with a 20/80 ratio by electrospinning, with capsaicin serving as the anticancer drug. The properties of the fabricated nanofibers were evaluated by field emission scanning electron microscopy. Also, gold nanoparticles were used to analyze and compare its effectiveness against the K562 cancer cell line. This cell line was prepared from Pasteur cell bank and cultured in DMEM medium. Subsequently, the anticancer effect of synthetic nanofibers in different concentrations was assessed by performing survival test, apoptosis by annexin and propidium iodide staining, and cell scratch assay. The electron microscopy study demonstrated the uniformity and purity of the nanofiber structure. The results showed that capsaicin, dose-dependently, reduced the viability of K562 cells after 72 h (P < 0.01). The apoptotic assay also indicated that the induction of apoptosis significantly increased by PVA/Cs/Caps(2 %) and PVA/Cs/Au(5 %)/Caps(10 %) compounds in the studied cell line (P < 0.0001). Furthermore, scratch assay at 24, 48, and 72 h demonstrated that the mentioned compounds possess anti-migration potential, particularly at 48 h. Our results suggest that capsaicin in nanofiber substrate can show anticancer properties against the K562 leukemia cell line. Therefore, this compound can be considered a potential candidate for the treatment of leukemia.
以壳聚糖和聚乙乙醇纳米纤维为底物,研究不同浓度(2 %、6 %和10 %)的红辣椒活性物质辣椒素对K562白血病细胞的抗癌作用。为此,以壳聚糖(Cs)和聚乙烯醇(PVA)聚合物为原料,以辣椒素为抗癌药物,采用静电纺丝法制备了20/80比例的纳米纤维。利用场发射扫描电镜对制备的纳米纤维的性能进行了评价。此外,还利用金纳米颗粒对K562癌细胞的杀伤效果进行了分析和比较。该细胞系由巴斯德细胞库制备,在DMEM培养基中培养。随后,通过存活实验、膜联蛋白和碘化丙啶染色细胞凋亡实验和细胞划痕实验来评估不同浓度合成纳米纤维的抗癌作用。电镜研究表明,纳米纤维结构均匀,纯度高。结果表明,辣椒素在72 h (P
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引用次数: 0
Dual-targeting exosome vaccine confers efficient protection against CVB3-induced myocarditis 双靶向外泌体疫苗可有效预防cvb3诱导的心肌炎。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-02 DOI: 10.1016/j.nano.2025.102865
Qinghui Cao , Yihui Ge , Tong Wang, Ke Lin, Sidong Xiong, Yan Yue
Coxsackievirus B3 (CVB3) is a common cause of viral myocarditis, necessitating the development of prophylactic vaccines.. AD-Exo, a dual-targeting exosome vaccine, was developed to induce immune responses via targeting draining lymph nodes (dLNs) and dendritic cells (DCs). By incorporating an albumin-binding domain (ABD) peptide and a DC-guiding peptide (DCpep) into our previous CVB3 exosome vaccine (Exo), the AD-Exo vaccine demonstrated superior immunogenicity. It efficiently bound to mouse serum albumin, amplified antigen enrichment in dLNs, and enhanced DC uptake and maturation. Subcutaneous immunization in mice elicited significantly higher CVB3-specific serum neutralizing IgG with greater affinity than Exo and single-targeting vaccines. It induced robust T cell proliferation and CTL responses, increasing IFN-γ-producing CD4+ and CD8+ T cells. Ultimately, the AD-Exo vaccine reduced cardiac viral load, minimized histopathological damage, and significantly improved survival in challenged mice. This strategy provided novel perspectives for the development of dual-targeting prophylactic vaccines against viral myocarditis.
柯萨奇病毒B3 (CVB3)是病毒性心肌炎的常见病因,需要开发预防性疫苗。AD-Exo是一种双靶向外泌体疫苗,通过靶向引流淋巴结(dln)和树突状细胞(dc)诱导免疫应答。通过将白蛋白结合域(ABD)肽和dc引导肽(DCpep)整合到我们之前的CVB3外泌体疫苗(Exo)中,AD-Exo疫苗显示出优越的免疫原性。它能有效地与小鼠血清白蛋白结合,增强dln中抗原的富集,并促进DC的摄取和成熟。小鼠皮下免疫诱导的cvb3特异性血清中和IgG明显高于Exo和单靶向疫苗。它诱导T细胞增殖和CTL反应,增加产生IFN-γ的CD4+和CD8+ T细胞。最终,AD-Exo疫苗降低了心脏病毒载量,减少了组织病理学损伤,并显著提高了小鼠的存活率。这一策略为病毒性心肌炎双靶向预防疫苗的开发提供了新的视角。
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引用次数: 0
Investigation of nanoparticle extravasation pathways in tumor vessel-on-a-chip devices 纳米颗粒在肿瘤血管芯片装置外渗途径的研究。
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-01 DOI: 10.1016/j.nano.2025.102863
Sergio Dávila , Alberto Martín-Asensio, Elena Sanz-de Diego, Jaime J. Hernández , Isabel Rodríguez
The pathways through which nanomedicines extravasate from the bloodstream into solid tumors remain a subject of active investigation. To elucidate this process, we examine the predominant transport mechanisms in vitro using a tumor-vessel-on-chip (TVoC) microfluidic model device. The device comprises a micro-vessel lined with human umbilical vein endothelial cells, positioned adjacent to a compartment containing a collagen-based extracellular matrix. The two compartments are separated by a row of micropillars, where an endothelial barrier naturally forms at the interface within the gaps. Here, transport of different nanoparticles is analyzed under simulated vascular flow conditions. Strengthening endothelial cell junctions to modulate barrier properties led to a nearly 50 % reduction in the permeability coefficient. Furthermore, disruption of intracellular pathways resulted in minimal nanoparticle permeability, which is consistent with the interpretation that the tested nanoparticles predominantly extravasate via the interendothelial route.
纳米药物从血流外渗进入实体肿瘤的途径仍然是一个积极研究的课题。为了阐明这一过程,我们使用肿瘤血管芯片(TVoC)微流控模型装置检查了体外主要的运输机制。该装置包括内衬人脐静脉内皮细胞的微血管,定位于含有胶原基细胞外基质的隔室附近。这两个隔间由一排微柱隔开,在缝隙内的界面处自然形成内皮屏障。本文分析了不同纳米颗粒在模拟血管流动条件下的输运。加强内皮细胞连接以调节屏障特性导致渗透系数降低近50% %。此外,细胞内通路的破坏导致纳米颗粒的渗透性最小,这与所测试的纳米颗粒主要通过内皮间途径外渗的解释一致。
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引用次数: 0
Targeting the PI3K/Akt/mTOR pathway with nanotechnology: A novel therapeutic strategy for gastrointestinal cancers 纳米技术靶向PI3K/Akt/mTOR通路:一种新的胃肠道肿瘤治疗策略
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-10-01 DOI: 10.1016/j.nano.2025.102861
Maryam Kaviani , Vahid Tayebi-Khorrami , Yegane Marami , Seyed Mahdi Hassanian
Gastrointestinal cancers are among the most common and deadly malignancies, with millions of fatalities annually. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling cascade is integral to the advancement, survival, and therapeutic resistance associated with gastrointestinal (GI) malignancies. Despite advancements in chemotherapy, challenges like drug resistance and side effects highlight the need for innovative treatments. Nanotechnology offers a promising solution by improving the precision and efficacy of therapies targeting this pathway while minimizing adverse effects. This review discusses the PI3K/Akt/mTOR pathway's role in gastrointestinal cancers and explores nanoparticle-based therapeutic approaches. Nanoparticles are classified into metal-based (e.g., selenium, gold, silver, iron oxide, and zinc oxide nanoparticles), lipid-based (e.g., liposomes, micelles, and solid lipid nanoparticles), and polymeric nanoparticles (e.g., dendrimers, nanospheres). Recent research on these approaches and ultra-small nanoparticles and superparticles is discussed along with their importance. This review also addresses the challenges, limitations, and prospects of the field.
胃肠道癌症是最常见和最致命的恶性肿瘤之一,每年有数百万人死亡。磷酸肌肽3-激酶(PI3K)/Akt/哺乳动物雷帕霉素靶点(mTOR)信号级联在胃肠道(GI)恶性肿瘤的进展、生存和治疗耐药中不可或缺。尽管化疗取得了进步,但耐药性和副作用等挑战凸显了对创新治疗方法的需求。纳米技术提供了一个很有前途的解决方案,它提高了靶向这一途径的治疗的准确性和有效性,同时最大限度地减少了副作用。本文讨论了PI3K/Akt/mTOR通路在胃肠道癌症中的作用,并探讨了基于纳米颗粒的治疗方法。纳米粒子分为金属纳米粒子(如硒、金、银、氧化铁和氧化锌纳米粒子)、脂质纳米粒子(如脂质体、胶束和固体脂质纳米粒子)和聚合物纳米粒子(如树状大分子、纳米球)。本文讨论了这些方法以及超小纳米粒子和超粒子的最新研究进展及其重要性。本文还讨论了该领域的挑战、局限性和前景。
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引用次数: 0
Polymeric nanoparticles for liver-targeted pituitary tumor-transforming gene 1 silencing in rats with chronic liver disease 聚合纳米颗粒用于慢性肝病大鼠肝靶向垂体肿瘤转化基因1的沉默
IF 4.6 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-09-25 DOI: 10.1016/j.nano.2025.102860
Meritxell Perramón , María Navalón-López , Guillermo Fernández-Varo , Gregori Casals , Joana Faneca , Manuel Macías-Herranz , Loreto Boix , Yiliam Fundora , Manuel Morales-Ruiz , Judit García-Villoria , Cristina Fornaguera , Salvador Borrós , Wladimiro Jiménez
Pituitary tumor transforming gene 1 (Pttg1) is upregulated in cirrhosis and hepatocarcinoma (HCC). We assessed the therapeutic effect of liver-targeted Pttg1 siRNA Retinol (Ret) pBAE nanoparticles (NPs) to treat these disturbances. Fibrosis was induced in Wistar rats by carbon tetrachloride inhalation and HCC by diethylnitrosamine injection. Ret pBAE NPs accumulated in hepatic tissue, close to zones positive for αSMA staining. Pttg1 interference increased mean arterial pressure, reduced portal hypertension and decreased collagen accumulation and inflammatory infiltrate in fibrotic rats. In HCC rats, Pttg1 silencing reduced liver to body weight ratio and hepatic proliferation and increased hepatic ATP production and serum glucose. This therapy effectively mitigated liver fibrosis and HCC progression in experimental models. The feasibility of this treatment was also demonstrated in human derived hepatic stellate cells and in ex vivo human cirrhotic livers underscoring the therapeutic potential of Pttg1 siRNA Ret pBAE NPs in addressing liver fibrosis and HCC.
垂体肿瘤转化基因1 (Pttg1)在肝硬化和肝癌中表达上调。我们评估了肝脏靶向Pttg1 siRNA视黄醇(Ret) pBAE纳米颗粒(NPs)治疗这些紊乱的疗效。吸入四氯化碳和注射二乙基亚硝胺诱导Wistar大鼠肝纤维化。肝组织中paenps聚集,靠近α - sma染色阳性区。Pttg1干扰使纤维化大鼠平均动脉压升高,门静脉高压降低,胶原积累和炎症浸润减少。在HCC大鼠中,Pttg1沉默降低肝体重比和肝脏增殖,增加肝脏ATP生成和血清葡萄糖。在实验模型中,该疗法有效地减轻了肝纤维化和HCC的进展。这种治疗的可行性也在人源性肝星状细胞和离体人肝硬化肝脏中得到证实,强调了Pttg1 siRNA Ret pbanps在治疗肝纤维化和HCC方面的治疗潜力。
{"title":"Polymeric nanoparticles for liver-targeted pituitary tumor-transforming gene 1 silencing in rats with chronic liver disease","authors":"Meritxell Perramón ,&nbsp;María Navalón-López ,&nbsp;Guillermo Fernández-Varo ,&nbsp;Gregori Casals ,&nbsp;Joana Faneca ,&nbsp;Manuel Macías-Herranz ,&nbsp;Loreto Boix ,&nbsp;Yiliam Fundora ,&nbsp;Manuel Morales-Ruiz ,&nbsp;Judit García-Villoria ,&nbsp;Cristina Fornaguera ,&nbsp;Salvador Borrós ,&nbsp;Wladimiro Jiménez","doi":"10.1016/j.nano.2025.102860","DOIUrl":"10.1016/j.nano.2025.102860","url":null,"abstract":"<div><div>Pituitary tumor transforming gene 1 (<em>Pttg1</em>) is upregulated in cirrhosis and hepatocarcinoma (HCC). We assessed the therapeutic effect of liver-targeted <em>Pttg1</em> siRNA Retinol (Ret) pBAE nanoparticles (NPs) to treat these disturbances. Fibrosis was induced in Wistar rats by carbon tetrachloride inhalation and HCC by diethylnitrosamine injection. Ret pBAE NPs accumulated in hepatic tissue, close to zones positive for αSMA staining. <em>Pttg1</em> interference increased mean arterial pressure, reduced portal hypertension and decreased collagen accumulation and inflammatory infiltrate in fibrotic rats. In HCC rats, <em>Pttg1</em> silencing reduced liver to body weight ratio and hepatic proliferation and increased hepatic ATP production and serum glucose. This therapy effectively mitigated liver fibrosis and HCC progression in experimental models. The feasibility of this treatment was also demonstrated in human derived hepatic stellate cells and in <em>ex vivo</em> human cirrhotic livers underscoring the therapeutic potential of <em>Pttg1</em> siRNA Ret pBAE NPs in addressing liver fibrosis and HCC.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"69 ","pages":"Article 102860"},"PeriodicalIF":4.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154710","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}
引用次数: 0
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