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Advancing RNA delivery with Ionizable lipid nanoparticles: the roles of microfluidics and machine learning. 利用可电离脂质纳米颗粒推进RNA递送:微流体和机器学习的作用。
IF 3.9 Pub Date : 2026-01-01 Epub Date: 2025-11-17 DOI: 10.1080/17435889.2025.2587715
Neda Rostami, Mehdi Alidadi, Haniye Barzegar, Farzaneh Namazifar, Hadi Noei, Soudabeh Hosseini, Vladimir N Uversky, Taha Ghantabpour

Ionizable lipid nanoparticles (iLNPs) have revolutionized Ribonucleic acid (RNA) therapeutics by enabling precise and efficient delivery of nucleic acids. However, their clinical translation remains challenged by batch-to-batch variability, complex lipid - RNA interactions, and stringent regulatory requirements. This review highlights how advanced microfluidic technologies address these issues by providing precise control over iLNP fabrication through engineered mixer geometries, optimized flow dynamics, and pH-dependent self-assembly. Comparative analyses of hydrodynamic flow focusing (HFF), and staggered herringbone mixers (SHM) demonstrate their distinct influence on particle size, polydispersity index (PDI), and encapsulation efficiency. Furthermore, the integration of design-of-experiments (DoE) methodologies, computational fluid dynamics (CFD) modeling, and machine learning (ML)-assisted optimization enables predictive formulation design and adaptive process control, enhancing reproducibility and scalability. Collectively, this review underscores microfluidics and ML as synergistic technologies that bridge laboratory innovation with Good Manufacturing Practice (GMP)-compliant, large-scale production paving the way for the next generation of intelligent, personalized RNA nanomedicines.

电离脂质纳米颗粒(iLNPs)通过精确和有效地递送核酸,彻底改变了核糖核酸(RNA)治疗方法。然而,它们的临床翻译仍然受到批次间可变性、复杂的脂质- RNA相互作用和严格的监管要求的挑战。这篇综述强调了先进的微流控技术是如何解决这些问题的,通过设计混合器的几何形状、优化的流动动力学和依赖ph的自组装来精确控制iLNP的制造。流体动力聚焦(HFF)和交错人字形混合器(SHM)的对比分析表明,它们对颗粒尺寸、多分散性指数(PDI)和封装效率有明显的影响。此外,实验设计(DoE)方法、计算流体动力学(CFD)建模和机器学习(ML)辅助优化的集成实现了预测性配方设计和自适应过程控制,增强了可重复性和可扩展性。总的来说,这篇综述强调了微流体和ML作为协同技术,将实验室创新与符合GMP的大规模生产连接起来,为下一代智能、个性化RNA纳米药物铺平了道路。
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引用次数: 0
Intranasal administration of thermoresponsive pterostilbene loaded nanoemulgel confers neuroprotection in a rat model of ischemic stroke. 在大鼠缺血性脑卒中模型中,鼻内给药热反应性紫檀芪纳米凝胶赋予神经保护作用。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1080/17435889.2025.2574384
Bhaskar Jyoti Dutta, Vishal Shivaji Patil, Vinod L Gaikwad, Sanjiv Singh

Purpose: To develop and characterize Pterostilbene (PT)-loaded nanoemulgel (PNEG) and to evaluate its effect in rat model of ischemic stroke.

Method: PT-loaded nanoemulsion (PNE) was developed and further coated with chitosan and poloxamer-407 to obtain PNEG. It was characterized for particle size, zeta potential, morphology, entrapment efficiency, viscosity, stability, and ex-vivo mucoadhesive strength. Safety was assessed via in-vitro cytotoxicity assays and ex-vivo nasal mucosal compatibility. The therapeutic efficacy of PNEG was evaluated in a rat model of ischemic stroke, with assessments including neurobehavioral performances, oxidative stress, mitochondrial ultrastructure and complex activity, and pro-inflammatory cytokine levels.

Results: PNEG exhibited particle size of 65.68 ± 0.66 nm with a zeta potential of 9.77 ± 1.2. The formulation demonstrated enhanced mucoadhesive strength and thermoresponsive viscosity, promoting prolonged nasal residence time. In-vitro and ex-vivo assessments confirmed the formulation's biocompatibility and non-toxicity. In-vivo, PNEG significantly enhanced neurological performance, including motor coordination, muscle strength, and cognition, while concurrently reducing oxidative stress, preserving mitochondrial integrity, and suppressing neuroinflammation in hippocampus and cortex of ischemic rats.

Conclusion: Intranasal PNEG enabled sustained PT delivery with robust neuroprotection in ischemic stroke, highlighting its promise as a clinically translatable strategy for targeted brain therapy.

目的:制备并表征载紫菀芪纳米凝胶(PNEG),并评价其在缺血性脑卒中大鼠模型中的作用。方法:制备负载pt的纳米乳液(PNE),再用壳聚糖和poloxomer -407包被制备PNE。对其粒度、zeta电位、形态、包封效率、粘度、稳定性和离体粘接强度进行了表征。通过体外细胞毒性试验和离体鼻黏膜相容性评估其安全性。在缺血性脑卒中大鼠模型中评估PNEG的治疗效果,包括神经行为表现、氧化应激、线粒体超微结构和复合物活性、促炎细胞因子水平。结果:PNEG的粒径为65.68±0.66 nm, zeta电位为9.77±1.2。该制剂表现出增强的粘接强度和热响应粘度,促进延长鼻腔停留时间。体外和离体评估证实了该制剂的生物相容性和无毒性。在体内,PNEG显著增强了缺血大鼠的神经功能,包括运动协调、肌肉力量和认知,同时减少氧化应激,保持线粒体完整性,抑制海马和皮层的神经炎症。结论:鼻内PNEG使缺血性卒中患者的持续PT传递具有强大的神经保护作用,突出了其作为靶向脑治疗的临床可转化策略的前景。
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引用次数: 0
Can nanotechnology be applied to the treatment of obstructive sleep apnea? 纳米技术能否应用于治疗阻塞性睡眠呼吸暂停?
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-09-11 DOI: 10.1080/17435889.2025.2558313
Dashdulam Davaanyam, Vsevolod Y Polotsky
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引用次数: 0
LPS-focused nanomedicine for potent antibacterial therapy. 以脂多糖为重点的纳米药物用于强效抗菌治疗。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-21 DOI: 10.1080/17435889.2025.2574839
Samraggi Choudhury, Roshni Rupashri Mishra, Sayani Maji, Khushi Arora, Manish Singh, Jibanananda Mishra, Jiban Jyoti Panda

A significant upsurge in antibiotic-resistant infections, mainly due to the Gram-negative bacteria (GNB), is a major global concern. These GNBs carry lipopolysaccharides (LPS), a complex outer membrane component that endows them with structural integrity and acts as a formidable barrier against most antibiotics. Targeting LPS has thus emerged as a promising frontier in antibacterial nanomedicine. This review explores the structure of LPS and its pivotal role in bacterial virulence and immune evasion. We have highlighted diverse nanoparticle-based strategies like antibodies, peptides, aptamers, and small molecules that selectively bind and neutralize the LPS. Additionally, we have tried to present the key mechanisms of action of these NPs, which include membrane disruption, neutralization of the endotoxin, etc. Overall, this review provides a clear picture of how LPS-targeting NPs could aid in combating drug-resistant and deadly infections in the future.

主要由革兰氏阴性菌(GNB)引起的抗生素耐药感染显著上升,是全球关注的一个主要问题。这些gnb携带脂多糖(LPS),这是一种复杂的外膜成分,赋予它们结构完整性,并作为对抗大多数抗生素的强大屏障。因此,靶向LPS已成为抗菌纳米药物的一个有前途的前沿。本文综述了脂多糖的结构及其在细菌毒力和免疫逃避中的关键作用。我们强调了多种基于纳米粒子的策略,如抗体、肽、适体和选择性结合和中和LPS的小分子。此外,我们试图提出这些NPs的关键作用机制,包括膜破坏,中和内毒素等。总的来说,这篇综述提供了一幅清晰的画面,说明以lps为目标的NPs在未来如何帮助对抗耐药和致命的感染。
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引用次数: 0
Treating venous malformations with nanomedicines. 纳米药物治疗静脉畸形。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-14 DOI: 10.1080/17435889.2025.2573627
Weimin Tang, Daniel S Kohane, Kathleen Cullion

Venous malformations (VMs) are congenital vascular anomalies that cause pain, bleeding, and functional impairment, yet current first-line therapies such as sclerotherapy and surgical resection are limited by complications and high recurrence rates. Nanomedicine provides a promising alternative by exploiting the enhanced permeation and retention (EPR)-like effect to achieve selective accumulation of nanoparticles (NPs) within VMs. Preclinical studies support the use of NPs not only for improved drug delivery but also for non-pharmacologic based treatment, such as photothermal therapy. Furthermore, active targeting strategies involving surface-functionalized NPs offer the potential for enhanced specificity and treatment efficacy. Despite these advances, clinical translation faces challenges such as heterogeneity in EPR efficiency, depth-limited delivery, and pediatric safety concerns. Continued efforts to create more effective, pediatric-specific drug delivery systems are essential for developing safer, more efficient, and minimally invasive nanomedicine therapy for patients with VMs.

静脉畸形(VMs)是一种先天性血管异常,可引起疼痛、出血和功能损害,但目前的一线治疗方法,如硬化疗法和手术切除,由于并发症和高复发率而受到限制。纳米药物通过利用增强的渗透和保留(EPR)样效应来实现纳米颗粒(NPs)在vm内的选择性积累,提供了一种有前途的替代方案。临床前研究支持NPs不仅用于改善药物输送,而且用于非药物治疗,如光热治疗。此外,涉及表面功能化NPs的主动靶向策略提供了增强特异性和治疗效果的潜力。尽管取得了这些进展,但临床翻译仍面临着挑战,如EPR效率的异质性、深度受限的分娩和儿科安全问题。继续努力创造更有效的儿科药物输送系统对于开发更安全、更有效和微创的纳米药物治疗VMs患者至关重要。
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引用次数: 0
Applying click chemistry principles to the design of tumor-targeted nanosystems. 将点击化学原理应用于肿瘤靶向纳米系统的设计。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-07 DOI: 10.1080/17435889.2025.2567837
J J Diaz-Mochon, R M Sanchez-Martin
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引用次数: 0
COX-2 gene silencing by laser-assisted oligonucleotides release from remote optical Nano-switches (LORONS) in hepatocellular carcinoma cells. 肝癌细胞中远程光学纳米开关(LORONS)激光辅助寡核苷酸释放的COX-2基因沉默。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-11-15 DOI: 10.1080/17435889.2025.2584581
Uzma Azeem Awan, Abida Raza, Shaukat Ali, Mostafa El Sayed

Background: Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocellular carcinoma (HCC). Selective inhibition of COX-2 can come forward as improved and targeted therapeutic strategy.

Methods: We hereby determine selective inhibition efficiency of COX-2 enzyme in HepG2 cells through laser-assisted oligonucleotides release from remote optical nano-switches (LORONS) with spatial and temporal control. Gold nanorods (GNRs) were decorated with fluorescein labeled single and double strand RNA interfering oligos through methoxy PEG thiol linkages. Upon uptake by HepG2 cell, conjugated GNRs were exposed to continuous NIR laser irradiation near the resonance wavelength of GNRs (808 nm) for controlled release of oligos.

Results: COX-2 protein expression was reduced by 93% after NIR laser exposure compared to control sample after 48 h (p < 0.05). Significant reduction in prostaglandin E2(PGE2) levels after LORONS treatment was also observed. Gene silencing efficacy using GNRs conjugated oligos without laser exposure was recorded 38%.

Conclusion: We hereby conclude LORONS as a useful therapeutic strategy for localized gene silencing by remote optical excitation at desired intracellular location.

背景:环氧化酶-2 (COX-2)的过表达与肝细胞癌(HCC)有关。选择性抑制COX-2可作为一种改进的靶向治疗策略。方法:通过时空控制的远程光学纳米开关(LORONS)释放激光辅助寡核苷酸,测定对HepG2细胞COX-2酶的选择性抑制效率。通过甲氧基聚乙二醇硫醇键,用荧光素标记的单链和双链RNA干扰寡核苷酸修饰金纳米棒。被HepG2细胞摄取后,将共轭gnr暴露在gnr共振波长(808 nm)附近的连续近红外激光照射下,以控制寡核苷酸的释放。结果:在近红外激光照射48小时后,COX-2蛋白的表达比对照样品降低了93% (p)。结论:我们由此得出LORONS是一种有效的治疗策略,可以通过在所需的细胞内位置进行远程光激发来实现局部基因沉默。
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引用次数: 0
Silver nanoparticles: a new frontier in ophthalmic innovation and treatment. 银纳米粒子:眼科创新和治疗的新前沿。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-08 DOI: 10.1080/17435889.2025.2571060
Tong Wang, Jian Cao, Fan Gan, Yupeng Zhang, Zhipeng You

In recent years, the application of nanotechnology in biomedicine has been extensively studied. Silver nanoparticles (AgNPs), a novel type of nanomaterial, have garnered increasing attention in the field of ophthalmology because of their unique antibacterial, anti-inflammatory, and wound healing properties. The research and development of AgNPs are driving innovations in ophthalmic treatment technologies and offering new solutions to address the challenges posed by traditional treatment methods. This article reviews the methods used to synthesize AgNPs, including physical, chemical, and biological approaches. A comprehensive literature search was performed in the PubMed and Web of Science databases for studies published up to 2025. Furthermore, it focuses on the applications of AgNPs in ophthalmology, including anti-infection, wound healing, antiangiogenic, and drug delivery systems. Finally, this article highlights the development trends and challenges of the use of AgNPs in ophthalmology, providing a theoretical basis and research direction for their future clinical application in this field.

近年来,纳米技术在生物医学中的应用得到了广泛的研究。银纳米颗粒(AgNPs)是一种新型纳米材料,由于其独特的抗菌、抗炎和伤口愈合性能,在眼科领域受到越来越多的关注。AgNPs的研究和开发正在推动眼科治疗技术的创新,并为解决传统治疗方法带来的挑战提供新的解决方案。本文综述了合成AgNPs的方法,包括物理方法、化学方法和生物方法。在PubMed和Web of Science数据库中进行了全面的文献检索,以获取截至2025年发表的研究。此外,重点介绍了AgNPs在眼科学中的应用,包括抗感染、伤口愈合、抗血管生成和药物输送系统。最后,本文重点阐述了AgNPs在眼科应用的发展趋势和面临的挑战,为其未来在该领域的临床应用提供了理论基础和研究方向。
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引用次数: 0
The rationality guidance index: a framework for reducing redundancy in nanomedicine innovation. 合理性引导指标:纳米医学创新中减少冗余的框架。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-23 DOI: 10.1080/17435889.2025.2576812
Aliasgar Shahiwala

Nanocarriers have transformed drug delivery by improving bioavailability, enabling targeted action, and reducing systemic toxicity. Despite these advances, the field has become saturated with structurally and functionally similar platforms, leading to redundancy and limited translational progress. This work critically analyzes the scientific and systemic drivers of redundancy, including design convergence, patent-driven modifications, novelty-focused academic incentives, and insufficient comparative standards. To address these challenges, a rational innovation framework is proposed, grounded in needs-based design, comparative benchmarking, predictive modeling, and resource-conscious decision-making. Within this framework, the Rationality Guidance Index (RGI) is introduced as a semi-quantitative pre-initiation triage tool that balances clinical need, innovation value, and translational feasibility. Designed for academic and innovator contexts, the RGI complements existing frameworks such as DELIVER and the 6Rs roadmap by identifying projects at high risk of redundancy before resource-intensive development. The adoption of rational innovation strategies, supported by structured decision-making tools, is essential to enhance clinical success rates and ensure that advances in nanomedicine translate into meaningful patient outcomes.

纳米载体通过提高生物利用度,实现靶向作用和降低全身毒性来改变药物递送。尽管取得了这些进步,但该领域已经饱和了结构和功能相似的平台,导致了冗余和有限的转化进展。这项工作批判性地分析了冗余的科学和系统驱动因素,包括设计趋同、专利驱动的修改、以新颖性为重点的学术激励以及缺乏比较标准。为了应对这些挑战,本文提出了一个基于需求的设计、比较基准、预测建模和资源意识决策的理性创新框架。在此框架内,引入合理性指导指数(RGI)作为一种半定量的启动前分诊工具,以平衡临床需求、创新价值和转化可行性。RGI专为学术和创新环境而设计,通过在资源密集型开发之前识别冗余高风险的项目,补充了诸如DELIVER和6r路线图等现有框架。采用由结构化决策工具支持的合理创新战略对于提高临床成功率和确保纳米医学的进步转化为有意义的患者结果至关重要。
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引用次数: 0
Lipid cubosome nanoparticles for drug delivery. 用于药物递送的脂质立方体纳米颗粒。
IF 3.9 Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1080/17435889.2025.2567841
Hayley C Parkin, Pawel Swietach, Helen Townley
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引用次数: 0
期刊
Nanomedicine (London, England)
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