Nanomedicine : nanotechnology, biology, and medicine最新文献

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 : 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

Black phosphorus-based drug nanocarrier for synergetic chemo-, chemo-dynamic, and photo-dynamic therapy of liver cancer 以黑磷为基础的药物纳米载体协同化疗、化疗动力和光动力治疗肝癌。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2025-12-07 DOI: 10.1016/j.nano.2025.102886

Jun Liu , Xiaoyu Hu , Qingrong Wang , Qiongkun Hu , Guanghao Yu , Yu Zhao , Liwei Gu , Jianying Shen , Qinghe Zhao , Feng Sui , Jingjing Zhu , Hai Ma

Limited therapeutic efficacy and significant toxicity consistently restrict the clinical development of chemotherapeutic drugs. To address these limitations, we engineered a multifunctional TAF-BP-DOX nanoplatform through the strategic combination of BP, doxorubicin, and a metal-polyphenol network (TAF). This rationally designed system exhibits dual responsiveness to tumor microenvironment characteristics, specifically acidic pH and elevated H₂O₂ levels. Upon NIR irradiation, the platform orchestrates a synergistic combination of chemotherapy, chemodynamic therapy, and photodynamic therapy, demonstrating markedly enhanced anti-hepatoma activity in both cellular and animal models compared to monotherapy approaches using either free DOX or TAF-DOX. Importantly, comprehensive evaluations revealed that the TAF-BP-DOX system not only improves therapeutic outcomes but also substantially mitigates the cardiotoxicity typically associated with DOX treatment. These collective findings position TAF-BP-DOX as a highly promising nanotherapeutic platform.

有限的治疗效果和显著的毒性一直制约着化疗药物的临床发展。为了解决这些限制，我们设计了一个多功能的TAF-BP- dox纳米平台，通过BP、阿霉素和金属多酚网络（TAF）的战略组合。这个合理设计的系统对肿瘤微环境特征具有双重响应性，特别是酸性pH和升高的H2O2水平。在近红外照射下，该平台协调化疗、化学动力治疗和光动力治疗的协同组合，与使用游离DOX或TAF-DOX的单一治疗方法相比，在细胞和动物模型中均显示出显著增强的抗肝癌活性。重要的是，综合评估显示，TAF-BP-DOX系统不仅改善了治疗结果，而且大大减轻了通常与DOX治疗相关的心脏毒性。这些共同的发现表明，TAF-BP-DOX是一种非常有前途的纳米治疗平台。

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引用次数: 0

PapMV nanoparticles: A novel pathway to SARS-CoV-2 protection, distinct from Imidazoquinolines PapMV纳米颗粒：一种不同于咪唑喹啉类药物的新型SARS-CoV-2保护途径

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2025-12-05 DOI: 10.1016/j.nano.2025.102887

Marilène Bolduc , Philippe Saint-Louis , Damien Carignan , Caroline Garneau , Yann Breton , Martin Pelletier , Anne Rancourt , Masahiko S. Satoh , Sachiko Sato , Mégan Gilbert , Henintsoa Rabezanahary , Mariana Baz , Isabelle Dubuc , Louis Flamand , Denis Leclerc

Toll-like receptor (TLR) 7/8 agonists, such as imidazoquinoline derivatives (IMDs), hold great potential as immune modulators that can boost innate antiviral and anticancer immunity. However, significant challenges persist in achieving sufficient efficacy while minimizing toxic side effects. To date, only imiquimod (IMQ) has received FDA approval, and its use is restricted to topical applications. Therefore, there is a significant need for novel and safe TLR 7/8 agonists. In response to this, we developed a new generation of TLR7/8 agonist, the PapMV nanoparticle (PapMV nano). IMDs and PapMV nano are both innate immune system-activating drugs that have demonstrated antiviral and anticancer activities, but they differ significantly in three key aspects: (1) composition (proteins and ssRNA for PapMV nano vs. synthetic molecules for IMDs), (2) structure (large nanoparticles vs. small molecules), and (3) the mechanism of cell entry (internalization for PapMV nano vs. cell diffusion for IMDs). To compare how immune cells react to these two types of drug products, we studied cell motility, cell metabolism, and the induction of apoptosis in human monocyte-derived macrophages (hMDMs). Our data reveal that PapMV nano enhances motility and mitochondrial respiration while decreasing glycolysis, whereas IMDs have no impact on motility and mitochondrial respiration but increase glycolysis. PapMV nano is also the only agonist that does not induce apoptosis. Although the cellular responses to these two types of agonists differ strikingly, both are capable of eliciting antiviral immunity. We confirmed this potential for PapMV nano by demonstrating its capacity to prevent SARS-CoV-2 infection, supporting its utilization as a safe and effective immune modulator, capable of providing broad protection against respiratory viruses.

toll样受体（TLR） 7/8激动剂，如咪唑喹啉衍生物（IMDs），作为免疫调节剂具有很大的潜力，可以增强先天抗病毒和抗癌免疫。然而，在实现充分疗效的同时尽量减少毒副作用方面仍然存在重大挑战。迄今为止，只有咪喹莫特（IMQ）获得了FDA的批准，其使用仅限于局部应用。因此，迫切需要新型安全的TLR 7/8激动剂。为此，我们开发了新一代TLR7/8激动剂——PapMV纳米颗粒（PapMV nano）。IMDs和PapMV纳米都是先天免疫系统激活药物，具有抗病毒和抗癌活性，但它们在三个关键方面存在显著差异：(1)组成（PapMV纳米与合成分子的蛋白质和ssRNA），(2)结构（大纳米颗粒与小分子），以及(3)细胞进入机制（PapMV纳米内化与细胞扩散）。为了比较免疫细胞对这两种药物的反应，我们研究了人类单核细胞源性巨噬细胞（hMDMs）的细胞运动、细胞代谢和凋亡诱导。我们的数据显示，PapMV纳米增强运动和线粒体呼吸，同时降低糖酵解，而IMDs对运动和线粒体呼吸没有影响，但增加糖酵解。PapMV纳米也是唯一不诱导细胞凋亡的激动剂。虽然细胞对这两种激动剂的反应明显不同，但两者都能够引发抗病毒免疫。我们通过展示其预防SARS-CoV-2感染的能力，证实了PapMV纳米的这种潜力，支持其作为一种安全有效的免疫调节剂，能够提供广泛的呼吸道病毒保护。

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引用次数: 0

Pharmacokinetic and biodistribution (PK/BD) study of ProGel-Dex, a thermoresponsive dexamethasone prodrug for sustained joint pain relief in a mouse model of osteoarthritis 热响应性地塞米松前药ProGel-Dex在骨关节炎小鼠模型中的药代动力学和生物分布（PK/BD）研究

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2025-12-04 DOI: 10.1016/j.nano.2025.102885

Xin Wei , Gang Zhao , Xiaoke Xu , Zhenshan Jia , Devendra Kumar , Evan Glissmeyer , Daniel Tran , Haochen Jiang , Sumbal Talib , Ningrong Chen , Zhulian Wang , Yazen Alnouti , Steven R. Goldring , Dong Wang

Intraarticular (IA) administration of ProGel-Dex was previously found to provide sustained joint pain relief with excellent safety in arthritis animal models. To explore ProGel-Dex’ working mechanisms, we conducted a comprehensive pharmacokinetics/biodistribution (PK/BD) study of IA ProGel-Dex and the free Dex released in an osteoarthritis mouse model. An initial “burst” release and distribution of ProGel-Dex was observed in all organs/tissues post IA administration. The higher-than-1.5 AUC_{inf_obs}/AUC_all ratios for both ProGel-Dex and free Dex support their long-term presence within the DMM joint beyond the experimental endpoint. The overall systemic organ/tissue exposures to ProGel-Dex and free Dex released were found to be much lower than those detected within the OA joint with IA ProGel-Dex. Together, these data support that the potent and long-sustained OA joint pain relief and the excellent safety of IA ProGel-Dex can be attributed to its prolonged retention in OA joint and the pathology-driven local activation.

先前在关节炎动物模型中发现，ProGel-Dex关节内（IA）给药可提供持续的关节疼痛缓解，并且具有良好的安全性。为了探索ProGel-Dex的作用机制，我们在骨关节炎小鼠模型中对IA ProGel-Dex和游离Dex进行了全面的药代动力学/生物分布（PK/BD）研究。在给药后，在所有器官/组织中观察到ProGel-Dex最初的“爆发”释放和分布。ProGel-Dex和游离Dex的AUCinf_obs/AUCall比值均高于1.5，支持它们在实验终点后长期存在于DMM关节内。整体系统器官/组织暴露于ProGel-Dex和游离释放的Dex比OA关节内检测到的ProGel-Dex要低得多。综上所述，这些数据支持IA ProGel-Dex的有效和长期持续的OA关节疼痛缓解和出色的安全性可归因于其在OA关节中的长期保留和病理驱动的局部激活。

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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 : 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。

{"title":"Enhanced cellular and transdermal delivery of the modified chromatin using gH625 cell-penetrating peptide","authors":"Xinghan Zhang, Yuxin Liang, Francesco Zonta, Jeong Hyeon Park","doi":"10.1016/j.nano.2025.102884","DOIUrl":"10.1016/j.nano.2025.102884","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"71 ","pages":"Article 102884"},"PeriodicalIF":4.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621415","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

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 : 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

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 : 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

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 : 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

Targeting prostate cancer through reactive oxygen species: Advances in photothermal and sonodynamic therapies 通过活性氧靶向前列腺癌：光热和声动力疗法的进展。

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine

Pub Date : 2025-11-23 DOI: 10.1016/j.nano.2025.102881

Ridha.M. Lefta , Samer Saleem Alshkarchy , Thekra F. Ali , Majid S. Jabir , Wesam R. Kadhum

Prostate cancer (PCa) remains a major clinical challenge due to limited treatment efficacy, frequent resistance, and high recurrence rates. Given the susceptibility of cancer cells to oxidative stress, reactive oxygen species (ROS)-based strategies offer promising therapeutic potential. Photothermal therapy (PTT) and sonodynamic therapy (SDT) are emerging minimally invasive modalities that exploit nanotechnology to induce localized ROS generation. This review highlights recent advances in ROS-mediated PTT and SDT for PCa, emphasizing nanomaterial design and functionalization to enhance targeting precision, drug delivery, and overcome tumor hypoxia. Combining PTT and SDT with chemotherapy, radiotherapy, or immunotherapy produces synergistic effects, potentially overcoming resistance and eliciting systemic antitumor immunity. Preclinical studies demonstrate effective tumor eradication and immune activation with minimal toxicity, suggesting promise for clinical translation. However, human clinical trials remain scarce, and further translational research is needed before these nanotechnology-based approaches can be integrated into standard PCa treatment.

前列腺癌（PCa）由于治疗效果有限、耐药频繁、复发率高，仍然是一个主要的临床挑战。鉴于癌细胞对氧化应激的易感性，基于活性氧（ROS）的策略提供了有希望的治疗潜力。光热疗法（PTT）和声动力疗法（SDT）是新兴的微创疗法，利用纳米技术诱导局部ROS生成。本文综述了ros介导的PTT和SDT治疗前列腺癌的最新进展，强调了纳米材料的设计和功能化，以提高靶向精度、药物传递和克服肿瘤缺氧。PTT和SDT联合化疗、放疗或免疫治疗可产生协同效应，潜在地克服耐药性并引发全身抗肿瘤免疫。临床前研究表明，有效的肿瘤根除和免疫激活，毒性最小，这表明有希望用于临床翻译。然而，人体临床试验仍然很少，在这些基于纳米技术的方法能够整合到标准的前列腺癌治疗之前，还需要进一步的转化研究。

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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 : 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