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Nasal Delivery of Phytochemicals Using Nanocarriers: Therapeutic Opportunities and Translational Challenges. 利用纳米载体鼻腔给药植物化学物质:治疗机会和转化挑战。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-16 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S564106
Simeon Ikechukwu Egba, Michael Osita Edeh, Nancy Oluomachi Uchenna, Matthew Chibunna Igwe, John Onyebuchi Ogbodo

The integration of phytochemicals with nanotechnology represents a promising approach to enhance nasal drug delivery, improving therapeutic efficacy and targeted brain delivery. This review explores recent advances in phytochemical-nanotechnology formulations and their applications in managing neurodegenerative diseases, respiratory disorders, and cancers. Phytochemicals such as curcumin, resveratrol, and quercetin exhibit potent pharmacological properties but suffer from poor solubility and limited bioavailability. Nanotechnology-based systems-including nanoparticles, liposomes, and nanoemulsions-overcome these drawbacks by improving stability, absorption, and controlled release. However, challenges such as nasal mucosa irritation, formulation complexity, regulatory barriers, and scalability still impede clinical translation. Notably, encapsulation of curcumin in polymeric nanoparticles has been shown to enhance its solubility and bioavailability, producing improved therapeutic outcomes in preclinical Alzheimer's models. Overall, this review underscores the synergistic potential of phytochemicals and nanotechnology in developing innovative nasal delivery platforms capable of providing targeted, effective, and patient-friendly treatment options for a range of medical conditions.

植物化学物质与纳米技术的结合代表了一种有前途的方法,可以增强鼻腔给药,提高治疗效果和靶向脑给药。本文综述了植物化学纳米制剂及其在治疗神经退行性疾病、呼吸系统疾病和癌症方面的应用的最新进展。植物化学物质如姜黄素、白藜芦醇和槲皮素表现出强大的药理特性,但其溶解性差,生物利用度有限。基于纳米技术的系统——包括纳米颗粒、脂质体和纳米乳液——通过提高稳定性、吸收性和控释来克服这些缺点。然而,诸如鼻黏膜刺激、配方复杂性、监管障碍和可扩展性等挑战仍然阻碍着临床转化。值得注意的是,将姜黄素包封在聚合纳米颗粒中可以提高其溶解度和生物利用度,从而改善临床前阿尔茨海默病模型的治疗效果。总的来说,这篇综述强调了植物化学物质和纳米技术在开发创新的鼻腔给药平台方面的协同潜力,这些平台能够为一系列医疗条件提供有针对性、有效和对患者友好的治疗选择。
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引用次数: 0
Progress in the Application of Nanobiotechnology in the Ablation Therapy of Hepatic Carcinoma. 纳米生物技术在肝癌消融治疗中的应用进展。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-15 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S551980
Zixuan Gao, Linmei Yao, Xin Wei, Shuojie Wang, Weihua Cao, Wen Deng, Xinxin Li, Ziyu Zhang, Shiyu Wang, Yaqin Zhang, Minghui Li, Yao Xie

Hepatocellular carcinoma (HCC) remains one of the most prevalent and lethal primary liver malignancies worldwide. Despite significant advances in surgical resection and local ablation therapies, challenges such as low early detection rates, high postoperative recurrence, and limited local tumor control persist in clinical practice. In recent years, the rapid advancement of nanobiotechnology has opened new avenues for precise diagnosis and personalized therapy of HCC. Owing to their excellent biocompatibility and functional tunability, various nanocarriers have been extensively explored in ablation-based treatments to achieve targeted drug delivery, controlled release, enhanced image guidance, and immune modulation. These innovations have substantially improved both the efficacy and safety of ablation therapies. This review focuses on recent progress in the application of nanobiotechnology to HCC ablation, systematically summarizing its mechanisms, innovative strategies, and future prospects across radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (CRA), high-intensity ultrasound focused ablation (HIFU), irreversible electroporation (IRE) and photothermal therapy (PTT). This review aims to comprehensively summarize recent advances in the application of nanobiomaterials-biocompatible and functionally engineered nanomaterials-in ablation-based therapies for HCC, emphasizing their roles in enhancing therapeutic efficacy, imaging guidance, and immune modulation.

肝细胞癌(HCC)仍然是世界范围内最常见和最致命的原发性肝脏恶性肿瘤之一。尽管手术切除和局部消融治疗取得了重大进展,但临床实践中仍然存在早期检出率低、术后复发率高、局部肿瘤控制有限等挑战。近年来,纳米生物技术的快速发展为肝癌的精确诊断和个性化治疗开辟了新的途径。由于其优异的生物相容性和功能可调性,各种纳米载体在消融治疗中被广泛探索,以实现靶向给药、控释、增强图像引导和免疫调节。这些创新大大提高了消融治疗的有效性和安全性。本文综述了纳米生物技术在肝细胞癌消融中的应用进展,系统总结了纳米生物技术在射频消融(RFA)、微波消融(MWA)、冷冻消融(CRA)、高强度超声聚焦消融(HIFU)、不可逆电穿孔(IRE)和光热治疗(PTT)等方面的应用机制、创新策略和未来前景。本文旨在全面总结纳米生物材料(生物相容性纳米材料和功能工程纳米材料)在HCC消融治疗中的应用进展,强调其在提高治疗效果、成像指导和免疫调节方面的作用。
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引用次数: 0
Bond-Centric Modifications of Hyaluronic Acid: Synthesis, Processing, and Biomedical Applications. 透明质酸键中心修饰:合成、加工和生物医学应用。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-15 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S560798
Anqi Yang, Pu Yang, Naisi Shen, Rui Wu, Xiangjun Liu, Yikun Ju, Lanjie Lei, Bairong Fang

Hyaluronic acid (HA), a natural polysaccharide present in human connective tissues, is widely used in biomedicine because of its excellent biocompatibility and biodegradability. However, products based on natural HA have several drawbacks, leading to widespread studies on the modification and processing of HA to improve its clinical use. This review discusses common methods of modifying HA, including physical and chemical modification as well as crosslinking. It focuses in detail on various chemical modification strategies from the perspective of the resultant chemical bonds, systematically organizes HA chemistry according to bond types, and refines the design rules for linking chemistry in relation to degradability, mechanical properties, responsiveness, and safety. It then summarizes the latest applications of HA-based products in the fields of ophthalmology, bone and joint treatment, aesthetic medicine, wound healing, and drug delivery. Finally, it explores challenges for the clinical application of HA and provides an outlook on future research directions. By summarizing the applications of HA across distinct biomedical domains, we hope to provide new ideas and directions for its further development and use.

透明质酸(Hyaluronic acid, HA)是一种存在于人体结缔组织中的天然多糖,因其具有良好的生物相容性和生物降解性而广泛应用于生物医学领域。然而,基于天然透明质酸的产品有几个缺点,导致对透明质酸的改性和加工的广泛研究,以提高其临床应用。本文综述了羟基磷灰石的常用改性方法,包括物理改性、化学改性和交联改性。它从生成的化学键的角度详细介绍了各种化学改性策略,根据键类型系统地组织了HA化学,并细化了与可降解性、机械性能、响应性和安全性相关的化学连接的设计规则。然后总结了基于ha的产品在眼科、骨关节治疗、美容医学、伤口愈合和药物输送等领域的最新应用。最后,探讨了HA临床应用面临的挑战,并对未来的研究方向进行了展望。通过对透明质酸在不同生物医学领域的应用进行综述,希望为其进一步的开发利用提供新的思路和方向。
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引用次数: 0
Recent Advances in Plant-Derived Extracellular Vesicles as Nanoparticles for Cancer Drug Delivery. 植物源性细胞外囊泡作为肿瘤药物递送纳米颗粒的研究进展。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-12 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S559440
Qiongdan Zhang, Huihong Duan, Yupei Yang, Huanghe Yu, Wei Wang, Bin Li

Plant-derived extracellular vesicles (PDEVs) have emerged as a highly promising and disruptive class of natural nanoparticles for anticancer drug delivery. This review provides a comprehensive analysis of PDEVs, positioning them within the broader landscape of nanomedicine through a direct comparison with conventional synthetic nanoparticles (eg, liposomes) and mammalian cell-derived extracellular vesicles (EVs). We highlight how the unique origin of PDEVs confers significant advantages, including superior natural biocompatibility, low immunogenicity, and the remarkable "dual-functionality" of acting as both inherent therapeutic agents and efficient drug carriers. The capacity of PDEVs to efficiently encapsulate a diverse range of therapeutic agents-from chemotherapeutic drugs and RNA interference molecules to gene-editing tools-is discussed in contrast to the more limited loading versatility and complex manufacturing of some alternative systems. The review systematically covers recent advances in PDEV isolation, characterization, and drug-loading techniques, emphasizing their demonstrated ability to cross biological barriers for targeted therapy and controlled release. Finally, we critically address the translational pathway, outlining key challenges in standardization and clinical translation, while forecasting their pivotal role in advancing personalized cancer nanomedicine. Through this comparative and functional perspective, PDEVs are poised to transition from a promising biological curiosity to a cornerstone of next-generation anticancer strategies.

植物源性细胞外囊泡(PDEVs)已成为一种极具潜力和破坏性的天然纳米颗粒,用于抗癌药物的递送。本综述对pdev进行了全面的分析,通过与传统的合成纳米颗粒(如脂质体)和哺乳动物细胞源性细胞外囊泡(ev)的直接比较,将它们定位在纳米医学的更广泛领域。我们强调PDEVs的独特来源如何赋予其显著的优势,包括优越的天然生物相容性,低免疫原性,以及作为固有治疗剂和有效药物载体的显着“双重功能”。讨论了pdev有效封装各种治疗药物的能力,从化疗药物和RNA干扰分子到基因编辑工具,与一些替代系统的更有限的装载多功能性和复杂的制造形成对比。本文系统地介绍了PDEV分离、表征和载药技术的最新进展,强调了它们在靶向治疗和控释方面跨越生物屏障的能力。最后,我们批判性地解决了转化途径,概述了标准化和临床转化中的关键挑战,同时预测了它们在推进个性化癌症纳米医学中的关键作用。从这个比较和功能的角度来看,PDEVs正准备从一个有前途的生物学好奇转变为下一代抗癌策略的基石。
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引用次数: 0
Deep Eutectic Solvents in Chronic Wound Management: Current Developments and Future Prospects. 慢性伤口处理中的深共晶溶剂:目前的发展和未来展望。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-12 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S572066
Rakesh Bastola, Raj Kumar Thapa

Chronic wounds pose a significant and growing global health challenge, affecting millions of individuals and often leading to prolonged suffering and increased healthcare costs. A major barrier to effective healing is wound infection, which disrupts the natural repair process and contributes to the chronicity. Therefore, innovative strategies for infection control are urgently required. Deep Eutectic Solvents (DESs) have recently gained attention as promising drug delivery systems owing to their multifunctional properties. In addition to serving as penetration enhancers that improve drug permeation, DESs exhibit intrinsic antimicrobial and antibiofilm activities, making them attractive candidates for managing infected wounds. This review highlights the fundamentals of DESs in the context of chronic wound management. It provides an overview of the wound healing process, pathophysiology of chronic wounds, and the role of biofilms in persistent infections. It further explores the dual role of DESs as penetration enhancers and antibiofilm agents, summarizing the recent DES-based formulations under investigation. Finally, this review discusses the current challenges and future prospects of integrating DESs into clinical practice. Collectively, DESs represent novel and versatile therapeutic platforms that have the potential to transform the treatment landscape of chronic wound healing.

慢性伤口是一项重大且日益严重的全球健康挑战,影响到数百万人,往往导致长期痛苦和医疗费用增加。有效愈合的主要障碍是伤口感染,它破坏了自然修复过程并导致慢性。因此,迫切需要创新的感染控制策略。深共晶溶剂(Deep共晶solvent, DESs)由于其多功能的特性,近年来作为一种很有前途的给药系统而受到人们的关注。除了作为提高药物渗透的渗透增强剂外,DESs还表现出内在的抗菌和抗生物膜活性,使其成为治疗感染伤口的有吸引力的候选者。这篇综述强调了DESs在慢性伤口处理中的基本原理。它提供了伤口愈合过程的概述,慢性伤口的病理生理学,以及生物膜在持续感染中的作用。它进一步探讨了DESs作为渗透增强剂和抗生物膜剂的双重作用,总结了最近正在研究的基于DESs的配方。最后,本综述讨论了将DESs纳入临床实践的当前挑战和未来前景。总的来说,DESs代表了新颖和多功能的治疗平台,有可能改变慢性伤口愈合的治疗前景。
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引用次数: 0
Key Clinical Frontiers of mRNA Loaded Lipid Nanoparticles in Cancer Vaccines. mRNA负载脂质纳米颗粒在癌症疫苗中的关键临床前沿。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-12 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S565558
Lili Cao, Jie Min, Meipin Yu, Zhongfeng Zhang, Dan Yuan, Dingchao Chen

Cancer vaccines are promising, but clinical translation is constrained by inefficient antigen delivery and suboptimal immune activation. Lipid nanoparticles (LNPs)-validated for potency and safety in COVID-19 mRNA vaccines-offer a versatile, scalable, and immunogenic platform. Key barriers persist: precise targeting of tumors or lymphoid tissues, efficient intracellular mRNA release, and the immunosuppressive tumor microenvironment. This review synthesizes design principles for mRNA-loaded LNPs, emphasizing lipid chemistry, organ-selective biodistribution, and nano-engineering strategies that strengthen antigen presentation and T-cell priming. We also examine combination approaches with checkpoint blockade, chemotherapy-induced immunogenic cell death, and molecular adjuvants. Clinically, signals of efficacy are emerging-most notably the KEYNOTE-942 study, in which mRNA-4157 combined with pembrolizumab showed a sustained improvement in recurrence-free survival at 5 years compared with pembrolizumab alone-highlighting both the potential and the remaining questions for this modality. Finally, we outline manufacturing and regulatory considerations and map future directions-including thermostable formulations, self-amplifying RNA, and AI-guided lipid discovery-to address translational bottlenecks and expand global access to LNP-based cancer vaccines.

癌症疫苗很有前景,但临床转化受到低效抗原递送和次优免疫激活的限制。脂质纳米颗粒(LNPs)在COVID-19 mRNA疫苗中的效力和安全性得到了验证,提供了一个通用的、可扩展的和免疫原性的平台。关键的障碍仍然存在:肿瘤或淋巴组织的精确靶向,细胞内mRNA的有效释放,以及免疫抑制肿瘤微环境。这篇综述综合了mrna负载LNPs的设计原则,强调脂质化学、器官选择性生物分布和纳米工程策略,以加强抗原呈递和t细胞启动。我们还研究了检查点阻断、化疗诱导的免疫原性细胞死亡和分子佐剂的联合方法。临床上,疗效的信号正在出现,最值得注意的是KEYNOTE-942研究,在该研究中,mRNA-4157联合派姆单抗与单独派姆单抗相比,5年无复发生存率持续改善,这突出了这种模式的潜力和剩余问题。最后,我们概述了制造和监管方面的考虑,并绘制了未来的方向——包括耐热配方、自我扩增RNA和人工智能引导的脂质发现——以解决翻译瓶颈,扩大基于lnp的癌症疫苗的全球可及性。
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引用次数: 0
Erratum: Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 [Corrigendum]. 伊维菌素黏液纳米悬浮液鼻喷雾剂减轻轻度COVID-19上呼吸道症状的临床、生化和分子评价[更正]。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-12 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S587907

[This corrects the article DOI: 10.2147/IJN.S313093.].

[这更正了文章DOI: 10.2147/IJN.S313093.]。
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引用次数: 0
Advancing Epigenetic Combination Therapy in Oncology: Multifunctional Nano-Drug Delivery Systems for Synergistic Efficacy and Precision Modulation. 肿瘤表观遗传联合治疗的进展:多功能纳米药物传递系统的协同效应和精确调节。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-11 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S566173
Tong Gao, Shunli Fu, Xianghua Quan, Jialin Sun, Man Jiang, Jing Li

Epigenetic modifications regulate gene expression at the transcriptional level, contributing to tumorigenesis and progression. While epigenetic-targeted combination therapies have gained prominence in oncology treatment management, their clinical efficacy remains constrained by differences in pharmacokinetics and biodistribution among combined agents. Nano-drug delivery systems (NDDS) demonstrate unique potential through co-delivery of therapeutic agents and optimization of their pharmacokinetic profiles. Furthermore, the development of multifunctional NDDS opens new possibilities for precision modulation in cancer treatment, offering valuable insights for clinical translation. Here, this review first outlined the intervention mechanisms of epigenetic dysregulation and analyzed the applications of epigenetic combination approaches. Subsequently, we highlight the transformative potential of NDDS in epigenetic combination therapy, with particular emphasis on how multifunctional NDDS design enables precise therapeutic regulation. This comprehensive analysis aims to advance the clinical translation of epigenetic-based combination strategies through innovative drug delivery solutions. In the future, with the continuous development of AI-driven NDDS design, biomimetic carriers, and dynamic epigenetic editing tools, it will be possible to overcome the clinical challenges of NDDS, enabling truly personalized cancer treatment.

表观遗传修饰在转录水平调控基因表达,促进肿瘤的发生和发展。虽然表观遗传靶向联合疗法在肿瘤治疗管理中取得了突出的地位,但其临床疗效仍然受到联合药物的药代动力学和生物分布差异的限制。纳米药物递送系统(NDDS)通过共同递送治疗剂和优化其药代动力学特征显示出独特的潜力。此外,多功能NDDS的发展为癌症治疗的精确调控开辟了新的可能性,为临床翻译提供了有价值的见解。本文首先概述了表观遗传失调的干预机制,并分析了表观遗传组合方法的应用。随后,我们强调了NDDS在表观遗传联合治疗中的变革潜力,特别强调了多功能NDDS设计如何实现精确的治疗调节。这项综合分析旨在通过创新的给药解决方案推进基于表观遗传学的联合策略的临床转化。未来,随着人工智能驱动的NDDS设计、仿生载体和动态表观遗传编辑工具的不断发展,将有可能克服NDDS的临床挑战,实现真正的个性化癌症治疗。
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引用次数: 0
Current Applications and Future Challenges of Mesenchymal Stem Cell-Extracellular Vesicles in Tissue Engineering: A Bibliometric Analysis. 间充质干细胞-细胞外囊泡在组织工程中的当前应用和未来挑战:文献计量学分析。
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-11 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S549684
Shuai Chen, Jingkai Di, Zhibo Zhang, Zijian Guo, Zui Tian, Yingda Qin, Yingi Long, Jiake Xu, Chuan Xiang, Fuyang Cao

Background: Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) are nano-sized vesicles and have become key mediators in tissue engineering and emerging therapeutic agents in regenerative medicine. This study systematically assessed the global research trend of MSCs-EVs for tissue engineering through bibliometric analysis of literature from 2014 to 2024.

Methods: A comprehensive search of Web of Science retrieved 752 eligible articles. We visualized and further analyzed collaboration, co-citation, co-authorship and co-occurrence through VOSviewer and Citespace, focusing on their application and future development trends.

Results: Annual publications increased continuously, with China and the United States accounting for 48.9% and 19.1% of research output, respectively, accompanied by intensive transnational cooperation. China leads in number of publications, number of years, total citations, H index and collaboration. The evolution of research trends confirms that the current field of application has expanded from cellular repair to drug delivery systems and biomaterial integration. Keyword cooccurrence reveals three clusters of research: artificial editing of exosomes (membranes), drug delivery (drugs, nucleic acids), and regeneration mechanisms (bone morphogenesis, angiogenesis regulation). The International Journal of Molecular Science became the most influential journal, and Shanghai Jiaotong University was a leader in institutional productivity.

Conclusion: This study is the first comprehensive quantitative analysis of tissue-engineered EVs and details trends and advances in tissue-engineered EVs research within the field of regenerative medicine. It portrays recent frontiers and hotspots, providing valuable insights for researchers in this particular area of research.

背景:来源于间充质干细胞(mscs - ev)的细胞外囊泡是一种纳米级囊泡,已成为组织工程中的关键介质和再生医学中的新兴治疗剂。本研究通过文献计量分析,系统评估了2014 - 2024年全球组织工程领域msc - ev的研究趋势。方法:综合检索Web of Science检索到752篇符合条件的文章。我们通过VOSviewer和Citespace对协作、共被引、合著和共现进行了可视化分析,重点分析了它们的应用和未来发展趋势。结果:年度发表量持续增加,中国和美国分别占研究产出的48.9%和19.1%,跨国合作密集。中国在论文发表数、发表年限、总被引数、H指数和合作方面均居世界领先地位。研究趋势的演变证实,目前的应用领域已经从细胞修复扩展到药物输送系统和生物材料整合。关键词共生揭示了三个研究集群:外泌体(膜)的人工编辑,药物传递(药物,核酸)和再生机制(骨形态发生,血管生成调节)。《国际分子科学杂志》成为最有影响力的期刊,上海交通大学在机构生产力方面处于领先地位。结论:本研究首次对组织工程化电动汽车进行了全面的定量分析,并详细介绍了再生医学领域组织工程化电动汽车研究的趋势和进展。它描绘了最近的前沿和热点,为这一特定研究领域的研究人员提供了有价值的见解。
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引用次数: 0
Hepatocyte-Targeted Epicatechin Nanoparticles Promote Autophagy and Enhance Mitochondrial Function in Metabolic Dysfunction-Associated Steatotic Liver Disease. 肝细胞靶向表儿茶素纳米颗粒促进代谢功能障碍相关脂肪变性肝病的自噬和增强线粒体功能
IF 6.5 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-12-11 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S557902
Daewon Han, Hyeji Lee, Solji Lee, Kyubae Lee, Nam-Kyung Lee, Tae-Eun Jin, Junguee Lee, Jong-Seok Kim, Do Kyung Kim, Jongdae Shin, Hwan-Woo Park

Introduction: Metabolic dysfunction-associated steatotic liver disease has limited treatment options, posing a serious global health challenge. Epicatechin (EC), a natural flavonoid, exhibits therapeutic potential; however, its clinical utility is hindered by its low solubility and limited bioavailability. Therefore, in this study, we developed liver-targeted EC-loaded galactosylated poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles (EC@PLGA-PEG-GAL NPs) with high therapeutic efficacy.

Methods: EC@PLGA-PEG-GAL NPs were synthesized, and their physicochemical properties, biocompatibility, and hepatocyte-targeted cellular uptake were characterized. The therapeutic efficacy of the NPs was assessed in high-fat diet (HFD)-fed mice, evaluating metabolic dysfunction and hepatic steatosis. Mechanistic studies were performed to investigate the effects on autophagic flux and mitochondrial function.

Results: The EC@PLGA-PEG-GAL NPs exhibited improved EC solubility, sustained drug release, and low cytotoxicity. In HFD-fed mice, administration of EC@PLGA-PEG-GAL NPs significantly ameliorated hepatic steatosis, reduced insulin resistance, and alleviated metabolic dysfunction, without causing toxicity. Mechanistically, these NPs restored the autophagic flux by activating the AMP-activated protein kinase pathway and inhibiting mechanistic target of rapamycin complex 1 signaling, thereby enhancing ubiquitinated protein clearance. They also alleviated mitochondrial dysfunction by enhancing the membrane potential, reducing the reactive oxygen species levels, and promoting mitochondrial biogenesis.

Conclusion: Our findings highlight EC@PLGA-PEG-GAL NPs as promising liver-targeted nanotherapeutics simultaneously modulating autophagy and mitochondrial functions in metabolic dysfunction-associated steatotic liver disease.

代谢功能障碍相关的脂肪变性肝病治疗方案有限,这是一个严重的全球健康挑战。表儿茶素(EC)是一种天然类黄酮,具有治疗潜力;然而,其低溶解度和有限的生物利用度阻碍了其临床应用。因此,在本研究中,我们开发了肝脏靶向负载的半乳糖基化聚(乳酸-羟基乙酸)-聚乙二醇纳米颗粒(EC@PLGA-PEG-GAL NPs),具有很高的治疗效果。方法:EC@PLGA-PEG-GAL合成NPs,并对其理化性质、生物相容性和肝细胞靶向细胞摄取进行表征。在高脂饮食(HFD)喂养的小鼠中评估NPs的治疗效果,评估代谢功能障碍和肝脂肪变性。机制研究探讨自噬通量和线粒体功能的影响。结果:EC@PLGA-PEG-GAL NPs具有更好的EC溶解度,持续的药物释放和低细胞毒性。在饲喂hfd的小鼠中,EC@PLGA-PEG-GAL NPs显著改善了肝脏脂肪变性,降低了胰岛素抵抗,减轻了代谢功能障碍,而没有引起毒性。在机制上,这些NPs通过激活amp激活的蛋白激酶途径和抑制雷帕霉素复合物1信号传导的机制靶点来恢复自噬通量,从而增强泛素化蛋白的清除。它们还通过提高膜电位、降低活性氧水平和促进线粒体生物发生来减轻线粒体功能障碍。结论:我们的研究结果强调EC@PLGA-PEG-GAL NPs是有希望的肝脏靶向纳米治疗药物,同时调节代谢功能障碍相关脂肪变性肝病的自噬和线粒体功能。
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引用次数: 0
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International Journal of Nanomedicine
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