Nanomedicine : nanotechnology, biology, and medicine最新文献_第4页

Evaluation of sources of variability in a nitric oxide screening assay for engineered nanomaterials 评估工程纳米材料的一氧化氮筛选试验的变异性来源。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-18 DOI: 10.1016/j.nano.2025.102878

Tariq Fahmi , Robert Gutierrez , Ana C. Barrios , Tae Joon Cho , John T. Elliott , Sanghamitra Majumdar , Bryant C. Nelson , Aaron C. Johnston-Peck , Alessandro Tona , Anil K. Patri , Elijah J. Petersen

Assays to detect potential biocompatibility issues can play a key role in supporting the development of new technologies such as medical products containing engineered nanomaterials (ENMs). A consensus test method standard on nitric oxide production after cellular ENM exposure was developed and published through ASTM International. In this paper, we describe an evaluation of sources of variability in this method. A significant challenge is ensuring that the protocol contains the necessary control measurements to account for potential issues when testing ENMs. Protocol testing was conducted during draft standard development and post-publication to better understand potential sources of variability such as the impact of insufficient removal of the ENM, the number of cells seeded, the selection of positive control compounds, and the culture techniques of the cells prior to the experiments. Several in-process control measurements were used to monitor the performance of intermediate steps in the assay procedure. Two gold nanoparticles with different surface coatings and nano-sized polystyrene particles were used to demonstrate the applicability of some of the control measurements. This testing revealed which sources of variability were more likely to have a significant impact on the overall assay uncertainty and confirmed the key importance of certain control measurements. These results could also support the standardization of other ENM-related in vitro methods that share similarities in their protocols with the method investigated here. The further development of this method can also support its use to evaluate the potential for substances other than ENMs to induce nitric oxide production.

检测潜在生物相容性问题的检测方法可以在支持新技术的开发方面发挥关键作用，例如含有工程纳米材料（enm）的医疗产品。关于细胞ENM暴露后一氧化氮产生的共识测试方法标准已通过ASTM国际组织制定和发布。在本文中，我们描述了这种方法中变异性来源的评估。一个重要的挑战是确保协议包含必要的控制度量，以在测试enm时考虑潜在的问题。在标准草案制定和出版后进行方案测试，以更好地了解潜在的可变性来源，如ENM去除不足的影响、接种细胞的数量、阳性对照化合物的选择以及实验前细胞的培养技术。几个过程中控制测量被用来监测分析过程中中间步骤的性能。用两种不同表面涂层的金纳米粒子和纳米聚苯乙烯粒子来证明一些控制测量的适用性。该测试揭示了哪些变异性来源更有可能对总体分析不确定度产生重大影响，并确认了某些控制测量的关键重要性。这些结果也可以支持其他与enm相关的体外方法的标准化，这些方法在协议上与本文研究的方法有相似之处。该方法的进一步发展也可以支持其用于评估除enm以外的物质诱导一氧化氮产生的潜力。

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引用次数: 0

Corrigendum to “tailored iron oxide nanoparticles for biomedical applications: Hydroxyethyl starch coating enhances endothelial biocompatibility” [nanomedicine: Nanotechnology, biology and medicine, volume 71, January 2026, 102880] “用于生物医学应用的定制氧化铁纳米颗粒：羟乙基淀粉涂层增强内皮生物相容性”的勘误表[纳米医学：纳米技术，生物学和医学，第71卷，2026年1月，102880]。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-12-20 DOI: 10.1016/j.nano.2025.102893

Lydia-Nefeli Thrapsanioti , Andrey N. Kuskov , Aikaterini Berdiaki , Anna L. Luss , Elizaveta R. Vlaskina , Anna V. Ivanova , Maxim A. Abakumov , Maria Marmara , Kalliope Plexousaki , Aristides Tsatsakis , Dragana Nikitovic

引用次数: 0

Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide 使用gH625细胞穿透肽增强修饰染色质的细胞和透皮递送

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-28 DOI: 10.1016/j.nano.2025.102884

Xinghan Zhang, Yuxin Liang, Francesco Zonta, Jeong Hyeon Park

Development of a transdermal drug delivery system must overcome the limited efficacy and reliability of current skin penetration methods. This study examined whether synthetic chromatin conjugated with the cell-penetrating peptide gH625 could traverse the epidermal barrier while maintaining cargo bioactivity. gH625-linked histone H2A assembled into chromatin was used to deliver DNA and peptides without penetration enhancers. gH625–chromatin increased cellular penetration by 150% compared with wild-type chromatin. Ex vivo porcine and in vivo mouse skin models demonstrated enhanced penetration depth up to 242 μm within 24 h, with signals confined to the dermis, indicating safe localized delivery. Epidermal growth factor (EGF) displayed at the histone H2B C-terminus maintained activity equivalent to free EGF, promoting cell growth, elevated COL1A1 secretion, and accelerated wound closure. These findings establish a chromatin-based nanoplatform for non-invasive transdermal delivery of bioactive macromolecules, filling a key gap in skin-targeted biotherapeutic delivery.

透皮给药系统的发展必须克服目前皮肤渗透方法有限的疗效和可靠性。本研究考察了与细胞穿透肽gH625结合的合成染色质是否能在保持货物生物活性的同时穿过表皮屏障。与gh625连接的组蛋白H2A组装成染色质，用于传递DNA和肽，而不需要渗透增强剂。与野生型染色质相比，gh625染色质增加了150%的细胞穿透性。离体猪和小鼠皮肤模型显示，24小时内穿透深度可达242 μm，信号局限于真皮层，表明安全的局部递送。组蛋白H2B c端显示的表皮生长因子（EGF）保持与游离EGF相当的活性，促进细胞生长，升高COL1A1分泌，加速伤口愈合。这些发现为生物活性大分子的非侵入性透皮递送建立了基于染色质的纳米平台，填补了皮肤靶向生物治疗递送的关键空白。

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引用次数: 0

Smart bioconjugated MOFs for targeted drug delivery: Albumin and globulin effects on mebeverine release dynamics 靶向药物递送的智能生物偶联mof：白蛋白和球蛋白对mebeverine释放动力学的影响

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1016/j.nano.2025.102882

Esra Maltas Cagil , Lola Yakhshilikova , Mustafa Ersoz

Mebeverine (MBV) is a clinically approved antispasmodic agent indicated for irritable bowel syndrome (IBS) that functions via direct calcium channel inhibition in gastrointestinal smooth muscle, alleviating spasmodic pain without central anticholinergic effects. Optimal oral delivery mandates protection from gastric acidity (pH ~1.5–3.0) and targeted release in the small intestine (pH ~6.0–7.4) for prompt onset and sustained action. Here, we report a comparative evaluation of tartaric acid–iron(III) metal–organic frameworks (TF-MOFs) functionalized with globulin (TF-GLB) or human serum albumin (TF-HSA), loaded with MBV. TF-GLB-MBV released a higher amount of MBV at 7.4 and 9.0, suggesting unsuitability for neutral and basic environments with a concentration of 2.06 mg (12.73 %) and 3.67 mg (22.69 %) at first 15 min, respectively. For TF-HSA-MBV, the maximum MBV release amounts were 3.58 mg (5.22 %) and 0.9 mg (21.20 %), respectively. This comparative kinetic modeling study reveals that TF-HSA-MBV performs optimally in acidic and alkaline environments, following Higuchi diffusion-based release. Meanwhile, TF-GLB-MBV is more suitable for mildly acidic pH, exhibiting Case II transport, suggesting erosion- or swelling-controlled release—ideal for upper intestinal targeting. However, neither formulation performed optimally at physiological pH (7.4), which may require further formulation optimization. These findings support TF-GLB as a promising oral delivery system for IBS.

Mebeverine （MBV）是一种临床批准的抗痉挛药物，用于肠易激综合征（IBS），通过直接抑制胃肠道平滑肌钙通道起作用，减轻痉挛性疼痛，无中枢抗胆碱能作用。最佳口服给药要求对胃酸（pH ~ 1.5-3.0）的保护和在小肠（pH ~ 6.0-7.4）的靶向释放，以迅速起效和持续作用。在这里，我们报告了一项比较评估，用球蛋白（TF-GLB）或人血清白蛋白（TF-HSA）功能化的酒石酸-铁（III）金属有机框架（TF-MOFs），装载MBV。tgf - glb -MBV释放量较高，为7.4 mg和9.0 mg，不适合中性和碱性环境，前15 min浓度分别为2.06 mg（12.73%）和3.67 mg（22.69%）。TF-HSA-MBV的最大释放量分别为3.58 mg（5.22%）和0.9 mg（21.20%）。该比较动力学模型研究表明，TF-HSA-MBV在酸性和碱性环境中表现最佳，以Higuchi扩散为基础释放。同时，TF-GLB-MBV更适合于轻度酸性pH，表现为病例II转运，表明侵蚀或肿胀控制释放是上肠靶向的理想选择。然而，两种配方在生理pH值（7.4）下均表现最佳，这可能需要进一步的配方优化。这些发现支持TF-GLB作为一种有前景的肠易激综合征口服给药系统。

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引用次数: 0

Multi-Organ-on-Chip approach to exploring breast cancer liver metastases concerning the endothelial barrier and the influence of immune cells 多器官芯片技术探讨乳腺癌肝转移的内皮屏障和免疫细胞的影响。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1016/j.nano.2025.102890

Joanna Konopka , Joanna Roszczyk , Elżbieta Jastrzębska , Agnieszka Żuchowska

Cancer metastasis is the spread of cancerous cells through the circulatory system to distant organs. Existing in vitro models remain insufficient to faithfully reproduce the metastatic process. Multi-Organ-on-Chip (multi-OoC) platforms allow the integration of complex tissue models. Here, we propose a microplatform that recapitulates breast cancer (BC) migration to the liver, considering an endothelial barrier (EB) and immune cell interactions. Tissue micromodels were created using agarose multi-wells, loaded into the microplatform, and separated by different types of barriers: (i) collagen type I, (ii) cell culture medium, (iii) immune (Jurkat) cells, (iv) a microvessel, and (v) a microvessel perfused with Jurkat cells. Spatial arrangement of cells, their morphology, and viability were imaged using fluorescence microscopy over 10-day experiments. Quantitative data such as Feret Diameter, relative Raw Integrated Density (ID) and migration distance of tumor cells (GFP-MDA-MB-231) were evaluated. The concentrations of metastatic agents (interleukin-6 (IL-6), and interleukin-11 (IL-11)) were determined using ELISA. The potential of a microplatform in drug screening was preliminarily assessed with the use of Doxorubicin (Dox) over a 7-day experiment. Changes in Feret diameter and ID indicated a gradual disintegration of the BC micromodel. BC cells migrated toward the liver micromodel through a barrier formed in the central microchannel. An EB was impenetrable for GFP-MDA-MB-231, whereas Jurkat cells promoted the migration of BC cells. Dox induced transient inflammation and suppressed IL-11-dependent pro-metastatic signaling, consistent with its dual cytotoxic and immunomodulatory roles.

癌症转移是指癌细胞通过循环系统向远处器官扩散。现有的体外模型仍不足以忠实地再现转移过程。多器官芯片（multi-OoC）平台允许复杂组织模型的集成。在这里，我们提出了一个微平台，概述乳腺癌（BC）迁移到肝脏，考虑到内皮屏障（EB）和免疫细胞相互作用。使用琼脂糖多孔创建组织微模型，将其加载到微平台中，并通过不同类型的屏障分离：(i) i型胶原蛋白，（ii）细胞培养基，（iii）免疫（Jurkat）细胞，（iv）微血管，(v)灌注Jurkat细胞的微血管。在10天的实验中，使用荧光显微镜对细胞的空间排列、形态和活力进行成像。对肿瘤细胞的Feret Diameter、相对Raw Integrated Density （ID）和迁移距离（GFP-MDA-MB-231）等定量数据进行评价。采用酶联免疫吸附法（ELISA）检测转移物白介素-6 （IL-6）、白介素-11 （IL-11）的浓度。通过使用阿霉素（Dox）进行为期7天的实验，初步评估了微平台在药物筛选中的潜力。Feret直径和ID的变化表明BC微模型逐渐解体。BC细胞通过中央微通道形成的屏障向肝脏微模型迁移。GFP-MDA-MB-231无法穿透EB，而Jurkat细胞促进BC细胞的迁移。Dox诱导短暂性炎症并抑制il -11依赖的促转移信号，这与它的双重细胞毒性和免疫调节作用一致。

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引用次数: 0

Enhancing intratumoral spread of radioluminescent nanoparticles via collagenase functionalization for radiation-induced photodynamic cancer therapy 通过胶原酶功能化增强放射发光纳米颗粒在肿瘤内的扩散，用于辐射诱导的光动力癌症治疗。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-23 DOI: 10.1016/j.nano.2025.102879

Sung-Ho Shin , Dhushyanth Viswanath , Haley A. Harper , Sandra E. Torregrosa-Allen , Carli J. McMahan , Alex E. Schwimmer , Bennett D. Elzey , You-Yeon Won

Radioluminescent nanoparticles enable radiotherapy- or X-ray-triggered photodynamic therapy (RT-PDT, also referred to as X-PDT in the literature) using the 5-aminolevulinic acid (ALA) prodrug, thereby overcoming the limited tissue penetration of conventional PDT. However, their therapeutic efficacy remains constrained by poor intratumoral nanoparticle distribution. To address this challenge, we developed collagenase-functionalized calcium tungstate nanoparticles capable of enzymatically degrading the extracellular matrix (ECM) in solid tumors. Micro-CT imaging revealed that collagenase functionalization increased intratumoral nanoparticle distribution by approximately sevenfold. In vivo studies further showed that enhanced penetration improved NP delivery, but that surface-bound maleimide linkers and collagenase partially scavenged reactive oxygen species (ROS), revealing a trade-off between ECM degradation and the quenching of ROS-mediated photodynamic effects. Overall, these findings demonstrates that collagenase-functionalized radioluminescent nanoparticles can effectively overcome stromal barriers in collagen-rich solid tumors, providing a promising strategy for next-generation RT-PDT while underscoring the importance of balancing enzymatic ECM remodeling with preservation of ROS generation.

放射发光纳米粒子使用5-氨基乙酰丙酸（ALA）前药，使放射治疗或x射线触发光动力治疗（RT-PDT，在文献中也称为X-PDT）成为可能，从而克服了传统PDT有限的组织穿透性。然而，它们的治疗效果仍然受到肿瘤内纳米颗粒分布不良的限制。为了解决这一挑战，我们开发了胶原酶功能化的钨酸钙纳米颗粒，能够酶降解实体肿瘤中的细胞外基质（ECM）。显微ct成像显示，胶原酶功能化使肿瘤内纳米颗粒分布增加了约7倍。体内研究进一步表明，增强的渗透改善了NP的递送，但表面结合的马来酰亚胺连接物和胶原酶部分清除了活性氧（ROS），揭示了ECM降解和ROS介导的光动力效应之间的权衡。总的来说，这些发现表明，胶原酶功能化的放射发光纳米颗粒可以有效地克服富含胶原的实体瘤中的基质屏障，为下一代RT-PDT提供了一种有希望的策略，同时强调了平衡酶促ECM重塑与保存ROS生成的重要性。

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引用次数: 0

Corrigendum to “a state-of-the-art review on inhalable nanoconjugates for targeted drug delivery in acute lung injury: Advances, challenges and future directions” [nanomedicine: Nanotechnology, biology and medicine, volume 70, November 2025, 102873] “用于急性肺损伤靶向药物递送的可吸入纳米偶联物的最新综述：进展、挑战和未来方向”[纳米医学：纳米技术，生物学和医学，第70卷，2025年11月，102873]。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI: 10.1016/j.nano.2025.102883

Piyushkumar Sadhu , Mamta Kumari , Nirmal Shah , Niyati Shah , Chitrali Talele , Falguni Rathod

引用次数: 0

RGD-Lipo@GOx: A nanotherapeutic strategy for targeting glycolysis and immune evasion in triple-negative breast cancer RGD-Lipo@GOx：针对三阴性乳腺癌的糖酵解和免疫逃避的纳米治疗策略。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-12-11 DOI: 10.1016/j.nano.2025.102889

Chao Zhu, Chenxu Guo, Ligong Zhang, Jun Qian, Mingliang Zhang

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy driven by glycolysis and immune evasion, with limited therapeutic options. This study develops RGD-modified glucose oxidase-loaded liposomes (RGD-Lipo@GOx) to target TNBC by modulating the MIF/NR3C2 axis, aiming to inhibit glycolysis and remodel the immune microenvironment. RGD-Lipo@GOx exhibited high encapsulation efficiency and tumor specificity. Bioinformatics analyses confirmed upregulated MIF and downregulated NR3C2 in TNBC. In vitro, RGD-Lipo@GOx suppressed glycolysis, migration, and invasion in MDA-MB-231 and BT-549 cells, upregulating NR3C2 and inhibiting MIF and PI3K/AKT signaling. In vivo, a TNBC xenograft model demonstrated enhanced tumor targeting, significant growth inhibition, and reduced glycolysis without systemic toxicity. These results highlight RGD-Lipo@GOx's potential as a nanotherapeutic platform that disrupts TNBC's metabolic and immune evasion mechanisms. Its high efficacy and safety suggest potential for clinical translation, particularly in combination with immunotherapies, and applicability to other glycolysis-driven cancers, advancing nanomedicine for precision oncology.

三阴性乳腺癌（TNBC）是一种高度侵袭性的恶性肿瘤，由糖酵解和免疫逃避驱动，治疗选择有限。本研究开发了rgd修饰的葡萄糖氧化酶负载脂质体（RGD-Lipo@GOx），通过调节MIF/NR3C2轴靶向TNBC，旨在抑制糖酵解并重塑免疫微环境。RGD-Lipo@GOx具有较高的包封效率和肿瘤特异性。生物信息学分析证实TNBC中MIF上调，NR3C2下调。在体外，RGD-Lipo@GOx抑制MDA-MB-231和BT-549细胞的糖酵解、迁移和侵袭，上调NR3C2，抑制MIF和PI3K/AKT信号。在体内，TNBC异种移植模型显示出增强的肿瘤靶向性，显著的生长抑制和糖酵解减少，无全身毒性。这些结果突出了RGD-Lipo@GOx作为纳米治疗平台的潜力，它可以破坏TNBC的代谢和免疫逃避机制。它的高疗效和安全性表明其具有临床转化的潜力，特别是与免疫疗法结合使用，并且适用于其他糖酵解驱动的癌症，推动纳米医学向精确肿瘤学发展。

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引用次数: 0

Protein-based biomaterials: Advances in structural design for drug delivery and regenerative medicine 基于蛋白质的生物材料：用于药物传递和再生医学的结构设计进展

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-10 DOI: 10.1016/j.nano.2025.102875

Muhammad Sohail , Mahtab Mirbolouk

The beneficial physical, chemical, and biological properties of proteins make them useful building blocks in the construction of biomedicals and nanomaterials. There are various biomaterials to develop inventive drug delivery systems ranging from simple to complex proteins which can be more efficient for patients undergoing surgical procedures. In the line of this article, the definition of medicine via proteins is based on complex bioengineering systems that mix tailored biomaterials with molecular algorithms to form controlled bioactive nanosystems. Among biomaterials, proteins are unique, because they can be found directly in nature, which qualify them easy for use, especially in surgical procedures. This article is aimed at describing their origin, structural properties, functions characteristics of interest in biology, and activity as drug delivery systems. Their native form and form of biomaterials i.e., hydrogels, scaffolds, membranes, fibers, and nanoparticles are examined. The article discusses novel designed nanoarchitectures aimed to solve long lasting problems in drug delivery like poor drug solubility, low bioavailability, and encapsulation of active pharmaceutical ingredients (APIs). The most important innovations are systems that respond to stimuli, mucoadhesive and mucus penetrating structures, lymphatic-targeting designs, and carriers that respond to environmental changes. Moreover, the article outlines the therapeutic uses of biomaterials based on proteins in tissue engineering (bone, cartilage, skin, cardiac, and neural tissue engineering), cancer treatment, diabetes, gene therapy, and in the treatment of inflammatory and chronically symptomatic disorders. Each part is arranged to minimize overlap and highlight functional distinctiveness to provide a cohesive design that integrates structure, function, and use. The review ends with the discussion of the existing gaps and the proposed pathways for future investigations which could facilitate the clinical translation of the work. This work serves as a stimulus toward the rational conception of protein-based materials and designed nanocarriers which are structurally tailored and application-driven, increasing their impact in the fields of drug delivery and regenerative medicine.

蛋白质有益的物理、化学和生物学特性使它们成为构建生物医学和纳米材料的有用基石。有各种各样的生物材料来开发从简单到复杂的蛋白质的创造性药物输送系统，这些系统可以更有效地为接受外科手术的患者提供服务。在本文中，通过蛋白质定义药物是基于复杂的生物工程系统，该系统将定制的生物材料与分子算法混合在一起，形成受控的生物活性纳米系统。在生物材料中，蛋白质是独一无二的，因为它们可以直接在自然界中找到，这使得它们易于使用，特别是在外科手术中。本文旨在描述它们的起源，结构特性，生物学中感兴趣的功能特征以及作为药物传递系统的活性。他们的天然形式和形式的生物材料，即水凝胶，支架，膜，纤维和纳米颗粒进行了检查。本文讨论了新型设计的纳米结构，旨在解决药物递送中长期存在的问题，如药物溶解度差、生物利用度低和活性药物成分（api）的封装。最重要的创新是对刺激作出反应的系统、粘液粘附和粘液穿透结构、淋巴靶向设计以及对环境变化作出反应的载体。此外，文章概述了基于蛋白质的生物材料在组织工程（骨、软骨、皮肤、心脏和神经组织工程）、癌症治疗、糖尿病、基因治疗以及炎症和慢性症状性疾病治疗中的治疗用途。每个部分的安排都尽量减少重叠，突出功能的独特性，提供一个整合结构，功能和使用的凝聚力设计。回顾以讨论现有差距和建议的未来研究途径结束，这可能有助于工作的临床翻译。这项工作为蛋白质基材料的合理概念和设计的纳米载体提供了刺激，这些纳米载体是结构定制和应用驱动的，增加了它们在药物输送和再生医学领域的影响。

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引用次数: 0

Nanoparticle distribution in the central nervous system following intrathecal administration: A multi-modal analysis of lumbar versus cisterna magna routes 鞘内给药后纳米颗粒在中枢神经系统中的分布：腰椎与大池路径的多模态分析。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1016/j.nano.2025.102877

Oluwatobi H. Babayemi , Corinne Fotso , Sauradip Chaudhuri , Lindsey K. Sablatura , Cassandra Baker , Fred Christian Velasquez , Janelle Morton , Eva Sevick-Muraca , Rachael W. Sirianni

Intrathecal drug delivery refers to the direct administration of compounds to cerebrospinal fluid (CSF), which can enhance delivery to the central nervous system (CNS) while minimizing peripheral exposure. Our prior work demonstrated that 100 nm, solid polystyrene nanoparticles surface modified with poly(ethylene glycol) (PEG) distribute within the CNS after intrathecal administration via the cisterna magna route (IT-CM). Here, we focus on comparing nanoparticle fate following administration to IT CM versus lumbar (IT-L) access points. We utilized dynamic a variety of imaging techniques to track the movement of model, ⁶⁴Cu-radiolabeled, fluorescent nanoparticles, hypothesizing that the IT-CM route would enable greater brain-localized delivery of nanoparticles when compared with the IT-L route. Spatiotemporal patterns of nanoparticle distribution and clearance were studied through a combination of quantitative positron emission tomography/computer tomography (PET/CT), fluorescent imaging (confocal microscopy), and biodistribution experiments (liquid scintillation counting). These studies revealed that: (1) the IT-CM route yielded greater brain-wide nanoparticle delivery while the IT-L route yielded greater spinal delivery, (2) the IT-CM route resulted in sustained retention of nanoparticles within the CNS and proximal lymphatics while the IT-L route resulted in higher nanoparticle clearance to peripheral organs, and (3) both the IT-CM and IT-L routes resulted in detectable though incomplete parenchymal delivery of nanoparticles, with the majority of signal remaining confined to the subarachnoid space. These findings underscore the pivotal role of intrathecal location in influencing nanoparticle biodistribution and clearance pathways within the CNS, identifying access point as an important design parameter when optimizing nanomedicine for intrathecal drug delivery.

鞘内给药是指将化合物直接给药到脑脊液（CSF）中，这可以增强对中枢神经系统（CNS）的递送，同时最大限度地减少外周暴露。我们之前的研究表明，100 nm的固体聚苯乙烯纳米颗粒表面经过聚乙二醇（PEG）修饰，在鞘内给药后通过大池途径（IT-CM）分布在中枢神经系统内。在这里，我们重点比较了给药后的纳米颗粒的命运在IT CM和腰椎（IT- l）接入点。我们利用各种动态成像技术来跟踪模型的运动，64cu放射性标记的荧光纳米颗粒，假设与IT-L途径相比，IT-CM途径能够实现更大的脑定位递送纳米颗粒。通过定量正电子发射断层扫描/计算机断层扫描（PET/CT）、荧光成像（共聚焦显微镜）和生物分布实验（液体闪烁计数），研究了纳米颗粒分布和清除的时空格局。这些研究表明：(1) IT-CM途径产生更大的全脑纳米颗粒递送，而IT-L途径产生更大的脊髓递送，(2)IT-CM途径导致纳米颗粒在中枢神经系统和近端淋巴管内持续保留，而IT-L途径导致更高的纳米颗粒对周围器官的清除，(3)IT-CM和IT-L途径都导致可检测到的纳米颗粒递送，尽管不完全。大部分信号仍局限于蛛网膜下腔。这些发现强调了鞘内位置在影响纳米颗粒在中枢神经系统内的生物分布和清除途径方面的关键作用，确定接入点是优化鞘内给药纳米药物的重要设计参数。

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引用次数: 0