Nano Today最新文献_第2页

Endogenous enzyme-activatable catalytic DNA nanodevice for cancer cell-selective piRNA imaging and regulation 内源性酶激活催化DNA纳米器件用于癌细胞选择性piRNA成像和调控

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-04 DOI: 10.1016/j.nantod.2025.102950

Ke Qin, Jiayin Zhao, Fei Ma, Chun-yang Zhang

As the newly identified epigenetic regulators, piwi-interacting RNAs (piRNAs) are garnering increasing attention due to their potential implications in tumorigenesis. However, cancer cell-selective detection and regulation of cancer-associated piRNAs remains a significant challenge because of their broad distribution in both malignant and normal cells. Herein, we develop an endogenous enzyme-activatable catalytic DNA nanodevice (EE-CDN) for cell-selective imaging and regulation of piRNA. The EE-CDN remains inert in normal cells, which minimizes nonspecific background signal and avoids unwanted side effects. The EE-CDN can be activated only in cancer cells to enable cell-specific piRNA recognition. By anchoring the sensing elements onto a tetrahedral DNA scaffold, the EE-CDN allows amplified detection of piRNA with accelerated kinetics via spatially confined catalytic DNA assembly. Taking advantage of single-molecule detection, the EE-CDN can achieve attomolar sensitivity, enabling accurate discrimination and molecular subtyping of breast cancer in both cellular models and clinical tissue specimens. Importantly, the EE-CDN can facilitate in vivo tracking of piRNA in living breast cancer cells and breast cancer-bearing mice with superior spatial specificity, and it can efficiently suppress tumor growth in cells and mice models via depletion of endogenous piRNA, offering a powerful platform for precise diagnosis of cancer and targeted therapy.

piwi相互作用rna （piRNAs）作为新发现的表观遗传调控因子，因其在肿瘤发生中的潜在作用而受到越来越多的关注。然而，癌症相关pirna的癌细胞选择性检测和调控仍然是一个重大挑战，因为它们在恶性和正常细胞中广泛分布。在此，我们开发了一种内源性酶激活催化DNA纳米装置（EE-CDN），用于细胞选择性成像和调节piRNA。EE-CDN在正常细胞中保持惰性，从而最大限度地减少非特异性背景信号并避免不必要的副作用。EE-CDN只能在癌细胞中激活，以实现细胞特异性piRNA识别。通过将传感元件固定在四面体DNA支架上，EE-CDN可以通过空间受限的催化DNA组装加速动力学放大piRNA的检测。利用单分子检测的优势，EE-CDN可以实现原子摩尔灵敏度，从而在细胞模型和临床组织标本中实现乳腺癌的准确鉴别和分子分型。重要的是，EE-CDN能够以优越的空间特异性促进活的乳腺癌细胞和乳腺癌小鼠体内piRNA的跟踪，并能通过消耗内源性piRNA有效抑制细胞和小鼠模型中的肿瘤生长，为癌症的精确诊断和靶向治疗提供强大的平台。

{"title":"Endogenous enzyme-activatable catalytic DNA nanodevice for cancer cell-selective piRNA imaging and regulation","authors":"Ke Qin, Jiayin Zhao, Fei Ma, Chun-yang Zhang","doi":"10.1016/j.nantod.2025.102950","DOIUrl":"10.1016/j.nantod.2025.102950","url":null,"abstract":"<div><div>As the newly identified epigenetic regulators, piwi-interacting RNAs (piRNAs) are garnering increasing attention due to their potential implications in tumorigenesis. However, cancer cell-selective detection and regulation of cancer-associated piRNAs remains a significant challenge because of their broad distribution in both malignant and normal cells. Herein, we develop an endogenous enzyme-activatable catalytic DNA nanodevice (EE-CDN) for cell-selective imaging and regulation of piRNA. The EE-CDN remains inert in normal cells, which minimizes nonspecific background signal and avoids unwanted side effects. The EE-CDN can be activated only in cancer cells to enable cell-specific piRNA recognition. By anchoring the sensing elements onto a tetrahedral DNA scaffold, the EE-CDN allows amplified detection of piRNA with accelerated kinetics via spatially confined catalytic DNA assembly. Taking advantage of single-molecule detection, the EE-CDN can achieve attomolar sensitivity, enabling accurate discrimination and molecular subtyping of breast cancer in both cellular models and clinical tissue specimens. Importantly, the EE-CDN can facilitate in vivo tracking of piRNA in living breast cancer cells and breast cancer-bearing mice with superior spatial specificity, and it can efficiently suppress tumor growth in cells and mice models via depletion of endogenous piRNA, offering a powerful platform for precise diagnosis of cancer and targeted therapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102950"},"PeriodicalIF":10.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Straight to the core: Intratumoral delivery of pitavastatin and miR-338–5p through lipid nanoparticles inhibits glioblastoma growth 直达核心：瘤内通过脂质纳米颗粒递送匹伐他汀和miR-338-5p可抑制胶质母细胞瘤的生长

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-03 DOI: 10.1016/j.nantod.2025.102954

João Basso , José Sereno , Ana Miguel Matos , Rui Oliveira , Maria Luísa Ramos , Miguel Castelo-Branco , Ana Fortuna , Rui Vitorino , Carla Vitorino

Over the last decades, only minimal therapeutic advances in the field of glioblastoma have been achieved. In spite of the approval of temozolomide, the 2-year survival rate of these patients is below 30 %. In this work, the development of cationic nanostructured lipid carriers (NLCs) for the co-delivery of pitavastatin and miR-338–5p, termed _PTNLCs:PAH:miR-338–5p, is explored. The results show an intracellular delivery of the cargo with subsequent transfection, target gene (NDFIP1, RHEB and PPP2R5A) knockdown and cytotoxicity at low µM concentrations of the carrier. This prototype also blocks spheroids growth within 72 h of treatment, resulting in the smallest cell aggregates (524 ± 40 µm vs. 1089 ± 29 µm for the control) at day 17. Biodistribution studies show an increased brain permeation for _PTNLCs after intravenous administration and a significant brain accumulation of _PTNLCs:PAH:miR-338–5p up to 48 h after one intracerebral injection. Lastly, the efficacy of the carriers was assessed in an orthotopic glioblastoma model through magnetic resonance imaging. After three local injections, the carrier was able to promote tumor regression, leading to 80 % of long-term survivors with a median survival over 60 days, contrasting to saline and temozolomide (12 and 41 days, respectively). Altogether, this preclinical proof of concept study opens new perspectives and supports the use of this prototype as a functional and effective tool for drug and gene delivery, with ability to respond to the aggressiveness of glioblastoma.

在过去的几十年里，在胶质母细胞瘤的治疗领域只取得了很小的进展。尽管替莫唑胺获批，但这些患者的2年生存率低于30% %。在这项工作中，探讨了用于共同递送匹伐他汀和miR-338-5p的阳离子纳米结构脂质载体（NLCs）的发展，称为ptnlc:PAH: miR-338-5p。结果显示，随后转染的货物在细胞内递送，靶基因（NDFIP1， RHEB和PPP2R5A）被敲低，并且在低µM浓度的载体下具有细胞毒性。该原型还在72 h内阻断球体生长，导致第17天的细胞聚集最小（524 ± 40 µm vs. 1089 ± 29 µm，对照组）。生物分布研究表明，静脉注射后ptnlc的脑渗透增加，ptnlc的脑蓄积显著：PAH: miR-338-5p在一次脑内注射后可达48 h。最后，通过磁共振成像在原位胶质母细胞瘤模型中评估载体的疗效。经过三次局部注射后，载体能够促进肿瘤消退，与生理盐水和替莫唑胺（分别为12天和41天）相比，80% %的长期幸存者的中位生存期超过60天。总之，这项临床前概念验证研究开辟了新的视角，并支持将该原型用作药物和基因传递的功能有效工具，具有应对胶质母细胞瘤侵袭性的能力。

{"title":"Straight to the core: Intratumoral delivery of pitavastatin and miR-338–5p through lipid nanoparticles inhibits glioblastoma growth","authors":"João Basso , José Sereno , Ana Miguel Matos , Rui Oliveira , Maria Luísa Ramos , Miguel Castelo-Branco , Ana Fortuna , Rui Vitorino , Carla Vitorino","doi":"10.1016/j.nantod.2025.102954","DOIUrl":"10.1016/j.nantod.2025.102954","url":null,"abstract":"<div><div>Over the last decades, only minimal therapeutic advances in the field of glioblastoma have been achieved. In spite of the approval of temozolomide, the 2-year survival rate of these patients is below 30 %. In this work, the development of cationic nanostructured lipid carriers (NLCs) for the co-delivery of pitavastatin and miR-338–5p, termed <sub>PT</sub>NLCs:PAH:miR-338–5p, is explored. The results show an intracellular delivery of the cargo with subsequent transfection, target gene (NDFIP1, RHEB and PPP2R5A) knockdown and cytotoxicity at low µM concentrations of the carrier. This prototype also blocks spheroids growth within 72 h of treatment, resulting in the smallest cell aggregates (524 ± 40 µm <em>vs</em>. 1089 ± 29 µm for the control) at day 17. Biodistribution studies show an increased brain permeation for <sub>PT</sub>NLCs after intravenous administration and a significant brain accumulation of <sub>PT</sub>NLCs:PAH:miR-338–5p up to 48 h after one intracerebral injection. Lastly, the efficacy of the carriers was assessed in an orthotopic glioblastoma model through magnetic resonance imaging. After three local injections, the carrier was able to promote tumor regression, leading to 80 % of long-term survivors with a median survival over 60 days, contrasting to saline and temozolomide (12 and 41 days, respectively). Altogether, this preclinical proof of concept study opens new perspectives and supports the use of this prototype as a functional and effective tool for drug and gene delivery, with ability to respond to the aggressiveness of glioblastoma.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102954"},"PeriodicalIF":10.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A magnetic hyperthermia-chemodynamic nanoreactor with ascorbic acid-enhanced reactive oxygen species regulation for anti-thrombosis therapy 抗坏血酸增强活性氧调控的磁热化学动力学纳米反应器用于抗血栓治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-03 DOI: 10.1016/j.nantod.2025.102951

Xuejiao Gong, Mengyun Yang, Xian Zheng, Hanyang Li, Guohao Li, Chendong Ji, Meizhen Yin

The synergy of reactive oxygen species (ROS) and heat has shown promise in enhancing thrombolysis by disrupting fibrin structure. However, precise control over the spatiotemporal distribution and dosage of ROS and heat at deep thrombus sites remains challenging. Here, we report an ascorbic acid (AA)-enhanced magnetic hyperthermia-chemodynamic therapy (MH-CDT) that exploits the concentration-dependent dual functionality of AA for precision thrombolysis. A dual-targeted magnetic nanoreactor (CMPV) was engineered to rapidly accumulate at the thrombus site via magnetic guidance and platelet membrane coating. AA facilitates the Fenton reaction for enhanced ROS generation to dissolve fibrin, while subsequently neutralizing excessive ROS to suppress inflammation during vascular repair. MH-CDT demonstrated thorough thrombus clearance and vascular recovery within 24 h without thrombosis recurrence in a mouse carotid artery thrombosis model. The combination between magnetic hyperthermia-induced fibrin disruption and AA-mediated ROS modulation enabled efficient thrombolysis while minimizing detrimental effects on the vascular endothelium. This AA-enhanced MH-CDT system provides a precise and effective thrombolytic strategy that overcomes depth limitations, showing promise for clinical translation.

活性氧（ROS）和热的协同作用已显示出通过破坏纤维蛋白结构来增强溶栓的希望。然而，精确控制血栓深部ROS和热量的时空分布和剂量仍然具有挑战性。在这里，我们报道了一种抗坏血酸（AA）增强磁热化学动力学治疗（MH-CDT），利用AA的浓度依赖的双重功能进行精确溶栓。设计了一种双靶向磁性纳米反应器（CMPV），通过磁引导和血小板膜涂层在血栓部位快速积聚。AA促进Fenton反应，增强ROS生成，溶解纤维蛋白，随后中和过多的ROS，抑制血管修复过程中的炎症。在小鼠颈动脉血栓形成模型中，MH-CDT在24 h内血栓清除彻底，血管恢复，无血栓复发。磁热诱导的纤维蛋白破坏和aa介导的ROS调节的结合使有效的溶栓成为可能，同时最大限度地减少对血管内皮的有害影响。这种aa增强的MH-CDT系统提供了一种精确有效的溶栓策略，克服了深度限制，显示出临床转化的希望。

{"title":"A magnetic hyperthermia-chemodynamic nanoreactor with ascorbic acid-enhanced reactive oxygen species regulation for anti-thrombosis therapy","authors":"Xuejiao Gong, Mengyun Yang, Xian Zheng, Hanyang Li, Guohao Li, Chendong Ji, Meizhen Yin","doi":"10.1016/j.nantod.2025.102951","DOIUrl":"10.1016/j.nantod.2025.102951","url":null,"abstract":"<div><div>The synergy of reactive oxygen species (ROS) and heat has shown promise in enhancing thrombolysis by disrupting fibrin structure. However, precise control over the spatiotemporal distribution and dosage of ROS and heat at deep thrombus sites remains challenging. Here, we report an ascorbic acid (AA)-enhanced magnetic hyperthermia-chemodynamic therapy (MH-CDT) that exploits the concentration-dependent dual functionality of AA for precision thrombolysis. A dual-targeted magnetic nanoreactor (CMPV) was engineered to rapidly accumulate at the thrombus site via magnetic guidance and platelet membrane coating. AA facilitates the Fenton reaction for enhanced ROS generation to dissolve fibrin, while subsequently neutralizing excessive ROS to suppress inflammation during vascular repair. MH-CDT demonstrated thorough thrombus clearance and vascular recovery within 24 h without thrombosis recurrence in a mouse carotid artery thrombosis model. The combination between magnetic hyperthermia-induced fibrin disruption and AA-mediated ROS modulation enabled efficient thrombolysis while minimizing detrimental effects on the vascular endothelium. This AA-enhanced MH-CDT system provides a precise and effective thrombolytic strategy that overcomes depth limitations, showing promise for clinical translation.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102951"},"PeriodicalIF":10.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MgFe-LDH-doped GelMA hydrogel scaffold repaired spinal cord injury via immunoregulation and enhancement of neuronal differentiation mgfe - ldh掺杂GelMA水凝胶支架通过免疫调节和增强神经元分化修复脊髓损伤

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/j.nantod.2025.102944

Shasha Zheng , Ruiqi Huang , Xugang Zhuang , Qian Zhu , Qingyue Cui , Hong Cheng , Wenyu Liang , Chenyu Du , Jing Li , Bin Zhang , Xin Gao , Yusong Wang , Pan Feng , Lei Tian , Yangnan Hu , Zuhong He , Rongrong Zhu , Renjie Chai

Spinal cord injury (SCI) is a traumatic condition of the nervous system that leads to severe disability. Its poor prognosis is largely attributed to uncontrolled inflammation and the intrinsically limited regenerative capacity of the spinal cord, which together severely restrict functional recovery. Hydrogel-based scaffolds represent a prospective strategy for SCI repair, offering structural support and a conducive microenvironment for regeneration. Here, we developed a gelatin methacrylate (GM) hydrogel scaffold incorporating MgFe-layered double hydroxide (LDH) nanoparticles functionalized with brain-derived neurotrophic factor (BDNF). This multifunctional GM-BDNF-LDH scaffold enables sustained release of BDNF, which promotes neuronal survival and regeneration, while LDH contributes additional therapeutic benefits through immunomodulation and neurogenic support. In both in vivo and in vitro experiments, LDH promoted the differentiation of neural stem cells (NSCs) while suppressing the expression of M1 markers and promoting the expression of M2 markers in microglia. Furthermore, the functional scaffold significantly improved motor function restoration, inflammation suppression, and neural differentiation in rats. Together, these results demonstrate that the LDH-functionalized scaffold we proposed can simultaneously modulate the immune microenvironment and promote neuronal regeneration, offering a potential treatment strategy for SCI recovery.

脊髓损伤（SCI）是一种神经系统的创伤性疾病，可导致严重的残疾。其预后不良很大程度上归因于不受控制的炎症和脊髓固有的有限再生能力，这两者共同严重限制了功能恢复。水凝胶基支架为脊髓损伤修复提供了一种有前景的策略，它提供了结构支持和有利于再生的微环境。在这里，我们开发了一种明胶甲基丙烯酸酯（GM）水凝胶支架，该支架将mgfe层状双氢氧化物（LDH）纳米颗粒与脑源性神经营养因子（BDNF）功能化。这种多功能GM-BDNF-LDH支架能够持续释放BDNF，促进神经元存活和再生，而LDH通过免疫调节和神经原性支持提供额外的治疗益处。在体内和体外实验中，LDH促进神经干细胞（NSCs）的分化，同时抑制小胶质细胞中M1标记物的表达，促进M2标记物的表达。此外，功能性支架可显著改善大鼠的运动功能恢复、炎症抑制和神经分化。总之，这些结果表明，我们提出的ldh功能化支架可以同时调节免疫微环境和促进神经元再生，为脊髓损伤恢复提供了一种潜在的治疗策略。

{"title":"MgFe-LDH-doped GelMA hydrogel scaffold repaired spinal cord injury via immunoregulation and enhancement of neuronal differentiation","authors":"Shasha Zheng , Ruiqi Huang , Xugang Zhuang , Qian Zhu , Qingyue Cui , Hong Cheng , Wenyu Liang , Chenyu Du , Jing Li , Bin Zhang , Xin Gao , Yusong Wang , Pan Feng , Lei Tian , Yangnan Hu , Zuhong He , Rongrong Zhu , Renjie Chai","doi":"10.1016/j.nantod.2025.102944","DOIUrl":"10.1016/j.nantod.2025.102944","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a traumatic condition of the nervous system that leads to severe disability. Its poor prognosis is largely attributed to uncontrolled inflammation and the intrinsically limited regenerative capacity of the spinal cord, which together severely restrict functional recovery. Hydrogel-based scaffolds represent a prospective strategy for SCI repair, offering structural support and a conducive microenvironment for regeneration. Here, we developed a gelatin methacrylate (GM) hydrogel scaffold incorporating MgFe-layered double hydroxide (LDH) nanoparticles functionalized with brain-derived neurotrophic factor (BDNF). This multifunctional GM-BDNF-LDH scaffold enables sustained release of BDNF, which promotes neuronal survival and regeneration, while LDH contributes additional therapeutic benefits through immunomodulation and neurogenic support. In both <em>in vivo</em> and <em>in vitro</em> experiments, LDH promoted the differentiation of neural stem cells (NSCs) while suppressing the expression of M1 markers and promoting the expression of M2 markers in microglia. Furthermore, the functional scaffold significantly improved motor function restoration, inflammation suppression, and neural differentiation in rats. Together, these results demonstrate that the LDH-functionalized scaffold we proposed can simultaneously modulate the immune microenvironment and promote neuronal regeneration, offering a potential treatment strategy for SCI recovery.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102944"},"PeriodicalIF":10.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxidase-catalyzed proximity labeling to survey the proteome of nanomaterial-cell interface during macropinocytosis-mediated internalization. 过氧化物酶催化近距离标记研究巨噬细胞介导内化过程中纳米材料-细胞界面的蛋白质组。

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 Epub Date: 2025-08-09 DOI: 10.1016/j.nantod.2025.102865

Yushuang Wei, Xiangyang Li, Yao Gong, Yue-Xuan Li, Jibin Guan, Bing Yuan, Yue Chen, Hong-Bo Pang

Nanomaterials often need to interact with proteins on the plasma membrane to get cross and access their intracellular targets. Therefore, to fully understand the cell entry mechanism, it is of vital importance to gain a comprehensive insight into the proteome at the interface when nanomaterials encounter the cells. Here, we reported a peroxidase-based proximity labeling method to survey the proteome at the nanoparticle (NP)-cell interface. Horseradish peroxidase (HRP) was conjugated to a variety of NPs and other ligand types while still being able to biotinylate the proteins surrounding NP (or ligand)-receptor complexes. Using two NP-based tracers for macropinocytosis (MP), which is highly relevant to NP internalization, we performed a proteomic survey and revealed the interface proteome difference between traditional and receptor-dependent MP. Moreover, our survey found that E-cadherin (CDH1), while not serving as the primary receptor, is present at the NP-cell interface and is functionally important for the cellular uptake of a wide variety of NPs. Overall, by integrating nanotechnology with proximity labeling, our study provides an approach to map the proteome of NP-cell interface for investigating the molecular mechanism of NP and macromolecule internalization into cells.

纳米材料通常需要与质膜上的蛋白质相互作用才能交叉并进入细胞内目标。因此，为了充分了解细胞进入机制，全面了解纳米材料与细胞接触时界面上的蛋白质组是至关重要的。在这里，我们报道了一种基于过氧化物酶的接近标记方法来研究纳米颗粒(NP)-细胞界面上的蛋白质组。辣根过氧化物酶（HRP）与多种NP和其他配体类型结合，同时仍然能够生物素化NP（或配体）-受体复合物周围的蛋白质。使用两种基于NP的巨噬细胞症（MP）示踪剂，研究人员进行了蛋白质组学调查，揭示了传统和受体依赖性MP之间的界面蛋白质组差异。此外，我们的研究发现，e -钙粘蛋白（CDH1）虽然不是主要受体，但存在于np -细胞界面，对细胞摄取多种np具有重要的功能。总的来说，通过纳米技术与接近标记的结合，我们的研究为研究NP和大分子内化进入细胞的分子机制提供了一种绘制NP-细胞界面蛋白质组的方法。

{"title":"Peroxidase-catalyzed proximity labeling to survey the proteome of nanomaterial-cell interface during macropinocytosis-mediated internalization.","authors":"Yushuang Wei, Xiangyang Li, Yao Gong, Yue-Xuan Li, Jibin Guan, Bing Yuan, Yue Chen, Hong-Bo Pang","doi":"10.1016/j.nantod.2025.102865","DOIUrl":"10.1016/j.nantod.2025.102865","url":null,"abstract":"<p><p>Nanomaterials often need to interact with proteins on the plasma membrane to get cross and access their intracellular targets. Therefore, to fully understand the cell entry mechanism, it is of vital importance to gain a comprehensive insight into the proteome at the interface when nanomaterials encounter the cells. Here, we reported a peroxidase-based proximity labeling method to survey the proteome at the nanoparticle (NP)-cell interface. Horseradish peroxidase (HRP) was conjugated to a variety of NPs and other ligand types while still being able to biotinylate the proteins surrounding NP (or ligand)-receptor complexes. Using two NP-based tracers for macropinocytosis (MP), which is highly relevant to NP internalization, we performed a proteomic survey and revealed the interface proteome difference between traditional and receptor-dependent MP. Moreover, our survey found that E-cadherin (CDH1), while not serving as the primary receptor, is present at the NP-cell interface and is functionally important for the cellular uptake of a wide variety of NPs. Overall, by integrating nanotechnology with proximity labeling, our study provides an approach to map the proteome of NP-cell interface for investigating the molecular mechanism of NP and macromolecule internalization into cells.</p>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":""},"PeriodicalIF":10.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inside Back Cover - Graphical abstract TOC/TOC in double column continued from OBC if required, otherwise blank page 封底内-图解摘要TOC/TOC双栏，如果需要，从OBC继续，否则空白页

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/S1748-0132(25)00313-5

引用次数: 0

Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information 封底外-图形摘要TOC/双栏TOC/封面图例（如适用），条形码，摘要和索引信息

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/S1748-0132(25)00314-7

引用次数: 0

Expanding the druggable proteome strategies and innovations in targeted protein degradation 扩展靶向蛋白质降解的可药物蛋白质组策略和创新

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-12-01 DOI: 10.1016/j.nantod.2025.102945

Ke Ma , Ting Liu , Wen-Bo Huan, Ke-Zheng Chen, Sheng-Lin Qiao

Targeted Protein Degradation (TPD) emerges as a novel therapeutic strategy that selectively eliminates disease-causing proteins by harnessing endogenous degradation systems, thereby overcoming the limitations of traditional drugs in addressing “undruggable” targets. This review outlines the core molecular mechanisms and primary technical platforms of TPD, including PROTACs, molecular glues (MGs), antibody-degradation conjugates, and emerging autophagy-related strategies (LYTACs, AUTACs, ATTECs, etc.). It systematically summarizes molecular engineering advances such as linker optimization, expansion of E3 ligase resources, and environmentally responsive and multi-modular designs. Furthermore, clinical and translational research cases demonstrate TPD's application potential across oncology, neurodegenerative diseases, cardiovascular disorders, and infectious diseases. Addressing challenges such as suboptimal pharmacokinetics, delivery limitations, potential off-target effects, and industrialization hurdles, we identify critical scientific questions requiring resolution and highlight emerging directions including AI-enabled design, nanomaterial delivery, and interdisciplinary integration. Overall, TPD is propelling drug development from “functional inhibition” toward “protein clearance,” injecting new vitality into precision medicine. This paper aims to provide a systematic reference for subsequent research and clinical translation.

靶向蛋白降解（Targeted Protein Degradation， TPD）作为一种新的治疗策略出现，它通过利用内源性降解系统选择性地消除致病蛋白，从而克服了传统药物在解决“不可药物”靶标方面的局限性。本文综述了TPD的核心分子机制和主要技术平台，包括PROTACs、分子胶（MGs）、抗体降解偶联物以及新兴的自噬相关策略（lytac、autac、attec等）。系统总结了分子工程方面的研究进展，如连接子优化、E3连接酶资源拓展、环境响应和多模块化设计等。此外，临床和转化研究案例证明了TPD在肿瘤、神经退行性疾病、心血管疾病和传染病方面的应用潜力。为了解决诸如次优药代动力学、递送限制、潜在脱靶效应和工业化障碍等挑战，我们确定了需要解决的关键科学问题，并强调了新兴方向，包括人工智能设计、纳米材料递送和跨学科整合。总的来说，TPD正在推动药物开发从“功能抑制”走向“蛋白质清除”，为精准医学注入新的活力。本文旨在为后续研究和临床翻译提供系统的参考。

{"title":"Expanding the druggable proteome strategies and innovations in targeted protein degradation","authors":"Ke Ma , Ting Liu , Wen-Bo Huan, Ke-Zheng Chen, Sheng-Lin Qiao","doi":"10.1016/j.nantod.2025.102945","DOIUrl":"10.1016/j.nantod.2025.102945","url":null,"abstract":"<div><div>Targeted Protein Degradation (TPD) emerges as a novel therapeutic strategy that selectively eliminates disease-causing proteins by harnessing endogenous degradation systems, thereby overcoming the limitations of traditional drugs in addressing “undruggable” targets. This review outlines the core molecular mechanisms and primary technical platforms of TPD, including PROTACs, molecular glues (MGs), antibody-degradation conjugates, and emerging autophagy-related strategies (LYTACs, AUTACs, ATTECs, etc.). It systematically summarizes molecular engineering advances such as linker optimization, expansion of E3 ligase resources, and environmentally responsive and multi-modular designs. Furthermore, clinical and translational research cases demonstrate TPD's application potential across oncology, neurodegenerative diseases, cardiovascular disorders, and infectious diseases. Addressing challenges such as suboptimal pharmacokinetics, delivery limitations, potential off-target effects, and industrialization hurdles, we identify critical scientific questions requiring resolution and highlight emerging directions including AI-enabled design, nanomaterial delivery, and interdisciplinary integration. Overall, TPD is propelling drug development from “functional inhibition” toward “protein clearance,” injecting new vitality into precision medicine. This paper aims to provide a systematic reference for subsequent research and clinical translation.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102945"},"PeriodicalIF":10.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper-doxorubicin nanodot-based dual catalytic metal prodrug liposome for enhanced chemotherapy and Chemodynamic Combination Therapychemodynamic combination therapy 基于铜-阿霉素纳米点的双催化金属前药脂质体用于强化化疗和化学动力联合治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-28 DOI: 10.1016/j.nantod.2025.102935

Chuanyong Fan , Yao Zhou , Yihua Mei, Kaifang Wu, Meng Wang, Limeng Chen, Hongyan Liu, Zehao Dong, Lu Xu

Although metal-based antitumor agents have for long been crucial components of most chemotherapy regimens, the majority of contemporary antitumor drugs have exhibited limited tumor selectivity and considerable off-target toxicity, restricting their therapeutic efficacy. Herein, metal prodrug nanodots (CD) comprising Cu^2 + and Doxorubicin (DOX) were first synthesized via coordination interaction. They were then co-loaded with Dihydroartemisinin (DHA) in a liposome nano-delivery system to enhance the metal drug’s selectivity and antitumor activity. The CD nanodots exhibited dual sensitivity to acid and Glutathione (GSH), which in turn, facilitated efficient tumor-specific drug release. Furthermore, the released Cu²⁺ could catalyze the endogenous H₂O₂ and loaded DHA, producing numerous toxic free radicals, which, in turn, induced lipid peroxidation and facilitated a synergistic antitumor effect of both Chemodynamic Therapy (CDT) and conventional chemotherapy. At the same time, Cu²⁺ decreased the GSH-mediated scavenging effect on the produced Reactive Oxygen Species (ROS) via a redox reaction, further enhancing the lethal effect of ROS on tumor cells. Given its potential clinical utility, this metal prodrug strategy could be leveraged for a safe and effective treatment of tumors.

虽然金属基抗肿瘤药物长期以来一直是大多数化疗方案的重要组成部分，但大多数当代抗肿瘤药物表现出有限的肿瘤选择性和相当大的脱靶毒性，限制了它们的治疗效果。本文首次通过配位相互作用合成了由Cu2 +和阿霉素（DOX）组成的金属药前纳米点（CD）。然后在脂质体纳米递送系统中与双氢青蒿素（DHA）共载，以增强金属药物的选择性和抗肿瘤活性。CD纳米点对酸和谷胱甘肽（GSH）具有双重敏感性，从而促进了肿瘤特异性药物的有效释放。此外，释放的Cu2+可以催化内源性H2O2和负载的DHA，产生大量有毒自由基，从而诱导脂质过氧化，促进CDT和常规化疗的协同抗肿瘤作用。同时，Cu2+降低了gsh对氧化还原反应产生的活性氧（Reactive Oxygen Species， ROS）的清除作用，进一步增强了ROS对肿瘤细胞的杀伤作用。鉴于其潜在的临床应用，这种金属前药策略可以用于安全有效的肿瘤治疗。

{"title":"Copper-doxorubicin nanodot-based dual catalytic metal prodrug liposome for enhanced chemotherapy and Chemodynamic Combination Therapychemodynamic combination therapy","authors":"Chuanyong Fan , Yao Zhou , Yihua Mei, Kaifang Wu, Meng Wang, Limeng Chen, Hongyan Liu, Zehao Dong, Lu Xu","doi":"10.1016/j.nantod.2025.102935","DOIUrl":"10.1016/j.nantod.2025.102935","url":null,"abstract":"<div><div>Although metal-based antitumor agents have for long been crucial components of most chemotherapy regimens, the majority of contemporary antitumor drugs have exhibited limited tumor selectivity and considerable off-target toxicity, restricting their therapeutic efficacy. Herein, metal prodrug nanodots (CD) comprising Cu<sup>2 +</sup> and Doxorubicin (DOX) were first synthesized via coordination interaction. They were then co-loaded with Dihydroartemisinin (DHA) in a liposome nano-delivery system to enhance the metal drug’s selectivity and antitumor activity. The CD nanodots exhibited dual sensitivity to acid and Glutathione (GSH), which in turn, facilitated efficient tumor-specific drug release. Furthermore, the released Cu<sup>2+</sup> could catalyze the endogenous H<sub>2</sub>O<sub>2</sub> and loaded DHA, producing numerous toxic free radicals, which, in turn, induced lipid peroxidation and facilitated a synergistic antitumor effect of both Chemodynamic Therapy (CDT) and conventional chemotherapy. At the same time, Cu<sup>2+</sup> decreased the GSH-mediated scavenging effect on the produced Reactive Oxygen Species (ROS) via a redox reaction, further enhancing the lethal effect of ROS on tumor cells. Given its potential clinical utility, this metal prodrug strategy could be leveraged for a safe and effective treatment of tumors.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102935"},"PeriodicalIF":10.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ROS/NO dual-releasing organic polymer nanoenzymes for NIR-II photo-adjuvant cancer immunotherapy ROS/NO双释放有机聚合物纳米酶用于NIR-II光辅助癌症免疫治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-11-25 DOI: 10.1016/j.nantod.2025.102936

Jiayao Ding , Long Wang , Fengshuo Wang , Yue Liu , Haidong Chen , Jingchao Li , Ting Su

Nitric oxide (NO) and reactive oxygen species (ROS) are crucial signal molecules in living systems, providing alternative strategies for cancer treatment other than chemotherapy drug. Nevertheless, the uncontrollable ROS/NO induction will lead to low therapeutic results and potential off-target effects. In this paper, ROS/NO dual-releasing organic polymeric nanoenzymes (O₂^·-/NO-SPN) are designed, capable of synergistically elevating ROS and NO levels in tumors upon second near-infrared (NIR-II) photo-triggered activation, thus establishing a photoactivated adjuvant strategy for enhanced cancer immunotherapy. A newly synthesized semiconducting polymer (L7) with an outstanding NIR-II photothermal performance is utilized as the core for fabricating such nanoenzymes. Using a film-dispersion technique coupled with hydration, a NO donor S-nitrosoglutathione (GSNO), superoxide anions (O₂^·-) donor 3-indoleacetic acid (3IAA) and L7 are co-loaded in a thermal-responsive nano-liposome, followed by surface embellishment of horseradish peroxidase (HRP). The formed O₂^·-/NO-SPN can generate local heat via NIR-II photothermal effect, and thus the thermal-responsive nano-liposomes are collapsed to release 3IAA, which is then catalyzed by HRP to produce O₂^·-, triggering tumor cell death in a NIR-II photodynamic-like manner. Moreover, the local heating effect results in production of NO by GSNO to further kill tumor cells and also activate the systemic immune responses through inducing immunogenic cell death and macrophage polarization. This ROS/NO dual-releasing strategy is demonstrated to effectively inhibit bilateral tumor growths and metastasis. The current study thereby offers a promising tool to regulate both ROS and NO levels concurrently in biological systems.

一氧化氮（NO）和活性氧（ROS）是生命系统中至关重要的信号分子，为癌症治疗提供了化疗药物以外的替代策略。然而，不可控的ROS/NO诱导将导致低治疗效果和潜在的脱靶效应。本文设计了ROS/NO双释放有机聚合物纳米酶（O2·-/NO- spn），在第二次近红外（NIR-II）光触发激活下，能够协同提高肿瘤中ROS和NO的水平，从而建立了一种增强癌症免疫治疗的光激活佐剂策略。一种新合成的半导体聚合物（L7）具有优异的NIR-II光热性能，被用作制造这种纳米酶的核心。利用膜分散技术和水合作用，将NO供体s -亚硝基谷胱甘肽（GSNO）、超氧阴离子（O2·-）供体3-吲哚乙酸（3IAA）和L7共负载在热响应的纳米脂质体中，然后在表面修饰辣根过氧化物酶（HRP）。形成的O2·-/NO-SPN通过NIR-II光热效应产生局部热量，热响应的纳米脂质体被分解释放3IAA， 3IAA被HRP催化生成O2·-，以类似NIR-II光动力学的方式触发肿瘤细胞死亡。此外，局部加热效应导致GSNO产生NO进一步杀伤肿瘤细胞，并通过诱导免疫原性细胞死亡和巨噬细胞极化激活全身免疫反应。这种ROS/NO双释放策略被证明能有效抑制双侧肿瘤的生长和转移。因此，目前的研究提供了一种有前途的工具来同时调节生物系统中的ROS和NO水平。

{"title":"ROS/NO dual-releasing organic polymer nanoenzymes for NIR-II photo-adjuvant cancer immunotherapy","authors":"Jiayao Ding , Long Wang , Fengshuo Wang , Yue Liu , Haidong Chen , Jingchao Li , Ting Su","doi":"10.1016/j.nantod.2025.102936","DOIUrl":"10.1016/j.nantod.2025.102936","url":null,"abstract":"<div><div>Nitric oxide (NO) and reactive oxygen species (ROS) are crucial signal molecules in living systems, providing alternative strategies for cancer treatment other than chemotherapy drug. Nevertheless, the uncontrollable ROS/NO induction will lead to low therapeutic results and potential off-target effects. In this paper, ROS/NO dual-releasing organic polymeric nanoenzymes (O<sub>2</sub><sup>·-</sup>/NO-SPN) are designed, capable of synergistically elevating ROS and NO levels in tumors upon second near-infrared (NIR-II) photo-triggered activation, thus establishing a photoactivated adjuvant strategy for enhanced cancer immunotherapy. A newly synthesized semiconducting polymer (L7) with an outstanding NIR-II photothermal performance is utilized as the core for fabricating such nanoenzymes. Using a film-dispersion technique coupled with hydration, a NO donor S-nitrosoglutathione (GSNO), superoxide anions (O<sub>2</sub><sup>·-</sup>) donor 3-indoleacetic acid (3IAA) and L7 are co-loaded in a thermal-responsive nano-liposome, followed by surface embellishment of horseradish peroxidase (HRP). The formed O<sub>2</sub><sup>·-</sup>/NO-SPN can generate local heat <em>via</em> NIR-II photothermal effect, and thus the thermal-responsive nano-liposomes are collapsed to release 3IAA, which is then catalyzed by HRP to produce O<sub>2</sub><sup>·-</sup>, triggering tumor cell death in a NIR-II photodynamic-like manner. Moreover, the local heating effect results in production of NO by GSNO to further kill tumor cells and also activate the systemic immune responses through inducing immunogenic cell death and macrophage polarization. This ROS/NO dual-releasing strategy is demonstrated to effectively inhibit bilateral tumor growths and metastasis. The current study thereby offers a promising tool to regulate both ROS and NO levels concurrently in biological systems.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102936"},"PeriodicalIF":10.9,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0