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Gas therapy in combating antimicrobial resistance: Mechanisms, synergistic strategies, and clinical translation challenges 气体疗法在对抗抗菌素耐药性:机制,协同策略,和临床翻译的挑战
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-15 DOI: 10.1016/j.nantod.2025.102960
Hongyang Lu , Wei He , Jiayu Li , Lingjun Zhang , Buyun Zhou , Qiang Zhou , Xiaowen Hu , Quazi T.H. Shubhra , Xiaosong He , Xiaojun Cai
The escalating prevalence of antimicrobial resistance (AMR), largely driven by the misuse and overuse of antibiotics, underscores the urgent need to explore alternative non-antibiotic therapeutic strategies. Gas therapy (GT), which utilizes gaseous signaling molecules (GSMs) such as carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H2S), oxygen (O2), and hydrogen (H2), has emerged as a promising antimicrobial strategy. These GSMs possess several distinctive advantages, including rapid and unimpeded diffusion into bacterial cells and biofilms, diverse antimicrobial mechanisms—such as reactive species generation, metabolic interference, and immune modulation—and a minimal risk of inducing AMR. This review systematically elucidates the antibacterial and anti-biofilm mechanisms of GSMs, emphasizing their integration with advanced modalities such as photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT) to enhance efficacy. We focus on how these strategies enable the precise delivery and controlled release of GSMs, how the released gases synergistically enhance therapeutic efficacy, and how these therapeutic platforms exhibit strong potential in combating infections caused by MDR bacteria and biofilm-associated pathogens. Despite preclinical success, critical barriers—including gas toxicity risks, biofilm penetration limitations, and regulatory hurdles—impede clinical translation. We further discuss future directions, advocating for engineered gas-releasing biomaterials, multimodal synergistic platforms, and artificial intelligence-driven design to optimize therapeutic outcomes. By bridging microbiology, nanotechnology, and clinical practice, this work underscores the potential of GT to redefine infection management in the post-antibiotic era.
抗生素耐药性(AMR)的流行程度不断上升,主要是由于抗生素的误用和过度使用,这突出表明迫切需要探索其他非抗生素治疗策略。气体疗法(GT)利用气体信号分子(GSMs),如一氧化碳(CO)、一氧化氮(NO)、硫化氢(H2S)、氧气(O2)和氢气(H2),已成为一种有前途的抗菌策略。这些gsm具有几个独特的优势,包括快速和畅通无阻地扩散到细菌细胞和生物膜,多种抗菌机制,如反应性物种产生,代谢干扰和免疫调节,以及诱导AMR的风险最小。本文系统阐述了GSMs的抗菌和抗生物膜机制,强调了其与光动力疗法(PDT)、光热疗法(PTT)、声动力疗法(SDT)和化学动力疗法(CDT)等先进疗法的结合,以提高疗效。我们重点关注这些策略如何实现gsm的精确递送和控制释放,释放的气体如何协同提高治疗效果,以及这些治疗平台如何在对抗耐多药细菌和生物膜相关病原体引起的感染方面显示出强大的潜力。尽管在临床前取得了成功,但包括气体毒性风险、生物膜渗透限制和监管障碍在内的关键障碍阻碍了临床转化。我们进一步讨论了未来的方向,倡导工程气体释放生物材料,多模态协同平台和人工智能驱动的设计,以优化治疗结果。通过连接微生物学、纳米技术和临床实践,这项工作强调了GT重新定义后抗生素时代感染管理的潜力。
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引用次数: 0
PNA aptamer-based bioreceptors for cardiac biomarker (cTnI) detection: Insight into the structural and stability-related aspects 基于PNA适配体的心脏生物标志物(cTnI)检测生物受体:洞察结构和稳定性相关方面
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-10 DOI: 10.1016/j.nantod.2025.102957
Francesco Basini , Abdellah Hambli , Subhankar Sahu , Rupali Bagale , Manova Santhosh Yesupatham , Christophe Ritzenthaler , David Montaigne , Eloise Woitrain , Henri Happy , Rabah Boukherroub , Wolfgang Knoll , Sabine Szunerits , Roberto Corradini
Aptamers, nucleic acid molecules that fold into specific three-dimensional structures, have been extensively used in the biosensing field to accomplish sensitive and specific monitoring of a wide range of biomarkers. Peptide nucleic acid (PNA), in this context, can be considered as a potential next-generation scaffold for aptamer synthesis and biomarker sensing, owing to its high stability in comparison to DNA counterparts. In this work, we investigated the performance of a series of PNA aptamers for monitoring of a prominent cardiac biomarker, cardiac troponin I (cTnI), using surface plasmon resonance (SPR) and showed that PNA sequences shorter than those previously reported for DNA can exhibit picomolar affinity, provided the essential structural features are preserved. Two different immobilization strategies (covalent and non-covalent) are validated in parallel for PNAs. The stability of sensor response in the presence of endonucleases such as DNase I was investigated further, as their occurrence in blood, plasma, and serum hydrolyses phosphodiester bonds and could be a limiting factor for point-of-care (PoC) application of DNA aptamers. Owing to their unnatural backbone, PNAs exhibited higher stability against DNase I in comparison to their DNA aptamer counterpart. Additionally, molecular dynamics (MD) simulations of DNA and PNA aptamers revealed similarities in their secondary structures, as well as distinctions in their propensity to adopt compact conformations. Overall, our findings not only provided a comprehensive framework for PNA design, surface functionalization, and cTnI biomarker detection using PNA-based bio-recognition scaffolds but also substantiated the biostability of PNAs, suggesting their high relevance for future PoC diagnostic applications.
核酸适体是一种折叠成特定三维结构的核酸分子,已被广泛应用于生物传感领域,以实现对各种生物标志物的敏感和特异性监测。在这种情况下,肽核酸(PNA)可以被认为是一种潜在的下一代适体合成和生物标志物传感支架,因为它与DNA相比具有很高的稳定性。在这项工作中,我们利用表面等离子体共振(SPR)研究了一系列PNA适体监测心脏生物标志物心肌肌钙蛋白I (cTnI)的性能,并表明PNA序列比先前报道的DNA序列短,只要保留基本结构特征,就可以表现出小摩尔亲和力。两种不同的固定策略(共价和非共价)在PNAs平行验证。在DNA酶I等内切酶存在的情况下,传感器反应的稳定性被进一步研究,因为它们存在于血液、血浆和血清中,可以水解磷酸二酯键,并可能成为即时(PoC)应用DNA适体的限制因素。由于它们的非自然骨架,与DNA适体相比,PNAs对DNA酶I表现出更高的稳定性。此外,DNA和PNA适配体的分子动力学(MD)模拟揭示了它们二级结构的相似性,以及它们倾向于采用紧凑构象的区别。总的来说,我们的研究结果不仅为PNA设计、表面功能化和使用基于PNA的生物识别支架检测cTnI生物标志物提供了一个全面的框架,而且证实了PNA的生物稳定性,这表明它们与未来PoC诊断应用具有很高的相关性。
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引用次数: 0
Lactolytic and TGFβ-inhibiting nanoplatform overcomes immunosuppression to enhance radiosensitivity in osteosarcoma 乳酸溶解和tgf β抑制纳米平台克服免疫抑制,增强骨肉瘤的放射敏感性
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-09 DOI: 10.1016/j.nantod.2025.102953
Linbang Wang , Jiaruo Tang , Rui Dou , Heng Zhang , Xiaomeng Cai , Yu Liu , Jingkun Liu , Xiaoguang Liu , Jiayu Zhang , Jun Chen
Osteosarcoma, the most prevalent malignant bone tumor in adolescents, presents significant clinical challenges due to its aggressive nature and resistance to conventional therapies including radiotherapy. Through analysis of human osteosarcoma specimens, we identified lactate and TGFβ as key regulators of the tumor microenvironment (TME), which collectively induce an immunosuppressive osteosarcoma microenvironment. To address this, we developed a novel multifunctional nanosystem constructed by genetically engineering lactate oxidase (LOX)-anchored platelet membranes to encapsulate manganese dioxide (MnO2) nanoparticles and the TGFβ inhibitor SB525334. This system demonstrates tumor-selective accumulation while simultaneously enabling lactate catabolism and TGFβ suppression. In vitro and in vivo studies confirmed that this synergistic approach effectively inhibits TGFβ-mediated signaling pathways and enhances T cell-mediated anti-tumor immunity. Furthermore, combination therapy with PD-L1 blockade significantly suppressed tumor growth and reduced recurrence rates, demonstrating robust adaptive immune responses. These findings highlight the transformative potential of engineered platelet membrane nanosystems in integrating metabolic modulation with immune regulation to improve current osteosarcoma treatment paradigms.
骨肉瘤是青少年中最常见的恶性骨肿瘤,由于其侵袭性和对包括放射治疗在内的常规治疗的耐药性,给临床带来了重大挑战。通过对人骨肉瘤标本的分析,我们发现乳酸和TGFβ是肿瘤微环境(TME)的关键调节因子,它们共同诱导免疫抑制性骨肉瘤微环境。为了解决这个问题,我们开发了一种新的多功能纳米系统,该系统通过基因工程乳酸氧化酶(LOX)锚定血小板膜来封装二氧化锰(MnO2)纳米颗粒和TGFβ抑制剂SB525334。该系统显示肿瘤选择性积累,同时使乳酸分解代谢和TGFβ抑制。体外和体内研究证实,这种协同方法有效抑制tgf β介导的信号通路,增强T细胞介导的抗肿瘤免疫。此外,PD-L1阻断联合治疗可显著抑制肿瘤生长并降低复发率,显示出强大的适应性免疫反应。这些发现强调了工程血小板膜纳米系统在整合代谢调节和免疫调节以改善当前骨肉瘤治疗范例方面的变革潜力。
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引用次数: 0
Synergistic composite engineering: Bridging immunomodulaftion, bone regeneration and precision therapy in osteosarcoma management 协同复合工程:骨肉瘤治疗中的桥接免疫调节、骨再生和精准治疗
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-08 DOI: 10.1016/j.nantod.2025.102952
Chaoqun You , Shuai Zhang , Jie Jiang , Jiuhui Xu , Fanwei Zeng , Tingting Ren , Yujing Li , Xiaodong Tang , Ran Wei
Osteosarcoma is the most common primary malignant bone tumor. It presents two major clinical challenges: aggressive tumor progression and extensive bone destruction. Traditional treatments often fail to achieve both complete tumor eradication and effective skeletal reconstruction. Recent advances in multifunctional composite biomaterials have made it possible to integrate tumor ablation, immune modulation, and bone regeneration into unified therapeutic systems. This review classifies these platforms according to material dimensionality (nanoscale, microscale, and macroscale) and examines targeted delivery strategies, including responsive release, external stimuli, and monofunctional optimization. We also highlight emerging synergistic systems that combine photothermal therapy, chemotherapy, metabolic interference, gene regulation, and mechanical support to produce coordinated therapeutic effects. Particular attention is given to metabolic–bone coupling and gene–mechanical synergy, which represent new strategies for simultaneously inhibiting tumor progression and promoting osteogenesis. Building on our original framework, we now map the osteosarcoma immune microenvironment and highlight precision immunoregulation enabled by materials, targeting T lymphocytes, natural killer cells, the axis of tumor associated macrophages and osteoclasts, and dendritic cells and B lymphocytes, to better couple tumor control with bone regeneration. Finally, we outline key translational challenges—such as mismatched degradation and therapeutic windows, tumor-promoting effects of osteogenic signaling, and biological heterogeneity—and propose future directions for developing precision-engineered, adaptive platforms for osteosarcoma management.
骨肉瘤是最常见的原发性骨恶性肿瘤。它提出了两个主要的临床挑战:侵袭性肿瘤进展和广泛的骨破坏。传统的治疗方法往往不能达到完全根除肿瘤和有效的骨骼重建。多功能复合生物材料的最新进展使得将肿瘤消融、免疫调节和骨再生整合到统一的治疗系统中成为可能。这篇综述根据材料维度(纳米尺度、微观尺度和宏观尺度)对这些平台进行了分类,并研究了有针对性的递送策略,包括响应性释放、外部刺激和单功能优化。我们还强调了结合光热疗法、化疗、代谢干扰、基因调控和机械支持的新兴协同系统,以产生协调的治疗效果。特别关注代谢-骨耦合和基因-机械协同,这代表了同时抑制肿瘤进展和促进成骨的新策略。在我们最初的框架的基础上,我们现在绘制骨肉瘤免疫微环境,并强调材料的精确免疫调节,靶向T淋巴细胞,自然杀伤细胞,肿瘤相关巨噬细胞和破骨细胞的轴,树突状细胞和B淋巴细胞,以更好地将肿瘤控制与骨再生结合起来。最后,我们概述了关键的转化挑战,如不匹配的降解和治疗窗口,成骨信号的肿瘤促进作用和生物异质性,并提出了开发精确工程的、适应性的骨肉瘤管理平台的未来方向。
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引用次数: 0
Bio-inspired functional motif nanoscale design for hard tissue regeneration: A review 仿生功能基序纳米级硬组织再生设计综述
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-08 DOI: 10.1016/j.nantod.2025.102958
Hui Yu , Yage Hou , Wutong Zhou , Lixin Sun , Liangyu Guo , Ning Wang , Panpan Pan , Jiacan Su , Jingdi Chen
Damage of hard tissue like bones and teeth has become an increasingly serious global problem in clinic. In-situ biomimetic mineralization strategy plays an indispensable role in hard tissue repair due to its advantages of imitating the mineralization process in vivo. Central to this process is the role of organic matrices in guiding the orderly arrangement of functional motifs at the nanoscale. Herein, this review focuses on the types of organic matrices and their regulatory effects on the in-situ assembly of hydroxyapatite-based functional motifs, emphasizing underlying mineralization mechanisms. Key mechanisms and pathways through which organic matrices control the oriented arrangement of functional motifs are discussed, along with strategies to enhance matrix-guided mineralization. Furthermore, various methods and applications of in-situ mineralization for hard tissue regeneration are comprehensively summarized. Finally, current challenges and future opportunities are presented, highlighting the potential of advanced technologies such as artificial intelligence and organoids in elucidating mechanisms and advancing applications of in-situ mineralization. It is hoped that this review will provide reference value for the design principles and development of hard tissue repair materials in the future.
骨、牙等硬组织的损伤已成为日益严重的全球性临床问题。原位仿生矿化策略具有模仿体内矿化过程的优点,在硬组织修复中发挥着不可替代的作用。这个过程的核心是有机基质在纳米尺度上引导功能基序有序排列的作用。本文综述了有机基质的类型及其对羟基磷灰石基功能基序原位组装的调节作用,并强调了潜在的矿化机制。讨论了有机基质控制功能基序定向排列的关键机制和途径,以及增强基质引导矿化的策略。综述了原位矿化技术在硬组织再生中的应用。最后,提出了当前的挑战和未来的机遇,强调了人工智能和类器官等先进技术在阐明原地矿化机制和推进应用方面的潜力。希望本文的综述对今后硬组织修复材料的设计原理和开发提供参考价值。
{"title":"Bio-inspired functional motif nanoscale design for hard tissue regeneration: A review","authors":"Hui Yu ,&nbsp;Yage Hou ,&nbsp;Wutong Zhou ,&nbsp;Lixin Sun ,&nbsp;Liangyu Guo ,&nbsp;Ning Wang ,&nbsp;Panpan Pan ,&nbsp;Jiacan Su ,&nbsp;Jingdi Chen","doi":"10.1016/j.nantod.2025.102958","DOIUrl":"10.1016/j.nantod.2025.102958","url":null,"abstract":"<div><div>Damage of hard tissue like bones and teeth has become an increasingly serious global problem in clinic. <em>In-situ</em> biomimetic mineralization strategy plays an indispensable role in hard tissue repair due to its advantages of imitating the mineralization process <em>in vivo</em>. Central to this process is the role of organic matrices in guiding the orderly arrangement of functional motifs at the nanoscale. Herein, this review focuses on the types of organic matrices and their regulatory effects on the <em>in-situ</em> assembly of hydroxyapatite-based functional motifs, emphasizing underlying mineralization mechanisms. Key mechanisms and pathways through which organic matrices control the oriented arrangement of functional motifs are discussed, along with strategies to enhance matrix-guided mineralization. Furthermore, various methods and applications of in-situ mineralization for hard tissue regeneration are comprehensively summarized. Finally, current challenges and future opportunities are presented, highlighting the potential of advanced technologies such as artificial intelligence and organoids in elucidating mechanisms and advancing applications of in-situ mineralization. It is hoped that this review will provide reference value for the design principles and development of hard tissue repair materials in the future.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102958"},"PeriodicalIF":10.9,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734046","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
Silver chalcogenide colloidal quantum dots for NIR-to-MWIR photodetection 用于近红外到mwir光探测的硫系银胶体量子点
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-06 DOI: 10.1016/j.nantod.2025.102956
Vishwa Bhatt , Abhishek Sharma , Min-Jae Choi
Infrared (IR) photodetectors are key components in modern optoelectronics, empowering applications across telecommunications, medical imaging, environmental monitoring, defense, and consumer electronics. Colloidal quantum dots (CQDs) have become promising semiconductors in response to growing demand for straightforward, affordable, high-performance, and environment-friendly infrared photo-sensing technologies. The growing attention in CQD-based IR photodetectors is because of their solution processability, spectral tunability, and compatibility with silicon-based platforms. Conventional-CQDs based on Pb, Hg, and Cd exhibit excellent performance, but pose usage/disposal challenges in everyday life as well as serious environmental and health risks. At this critical juncture, binary (Ag2X; X = S, Se, Te) and ternary (AgBiX2) silver chalcogenide CQDs have gained attention as RoHS-compliant substitutes. For near-to-mid IR detection, silver chalcogenide CQDs offer tunable bandgaps with strong absorption coefficients and favorable optoelectronic characteristics. Review highlights advance in Ag2X and AgMX2 CQDs IR photodetectors, examining their integration into photodetectors device-architecture based on their optoelectronic properties. Role of controlled stoichiometry, surface passivation, and interface-engineering in enhancing photodetector performance is emphasized. With global market for CQDs IR photodetectors projected to achieve milestones, this work presents thorough overview of CQD IR photodetectors, encompassing recent advancements, prevailing challenges, and prospective directions for future development.
红外(IR)光电探测器是现代光电子技术的关键部件,为电信、医疗成像、环境监测、国防和消费电子产品的应用提供了支持。胶体量子点(CQDs)已经成为有前途的半导体,以响应对简单,经济,高性能和环保的红外光传感技术日益增长的需求。基于cqd的红外探测器由于其溶液可加工性、光谱可调性以及与硅基平台的兼容性而受到越来越多的关注。基于铅、汞和镉的常规cqds具有优异的性能,但在日常生活中存在使用/处置挑战,并存在严重的环境和健康风险。在这个关键时刻,二元(Ag2X; X = S, Se, Te)和三元(AgBiX2)银硫系CQDs作为符合rohs的替代品受到了关注。对于近中红外探测,硫系银cqd提供了可调谐的带隙,具有强吸收系数和良好的光电特性。综述了Ag2X和AgMX2 CQDs红外光电探测器的进展,根据其光电特性研究了它们与光电探测器器件结构的集成。强调了控制化学计量学、表面钝化和界面工程在提高光电探测器性能方面的作用。随着CQD红外光电探测器的全球市场预计将达到里程碑,本工作对CQD红外光电探测器进行了全面的概述,包括最近的进展,当前的挑战和未来发展的前景方向。
{"title":"Silver chalcogenide colloidal quantum dots for NIR-to-MWIR photodetection","authors":"Vishwa Bhatt ,&nbsp;Abhishek Sharma ,&nbsp;Min-Jae Choi","doi":"10.1016/j.nantod.2025.102956","DOIUrl":"10.1016/j.nantod.2025.102956","url":null,"abstract":"<div><div>Infrared (IR) photodetectors are key components in modern optoelectronics, empowering applications across telecommunications, medical imaging, environmental monitoring, defense, and consumer electronics. Colloidal quantum dots (CQDs) have become promising semiconductors in response to growing demand for straightforward, affordable, high-performance, and environment-friendly infrared photo-sensing technologies. The growing attention in CQD-based IR photodetectors is because of their solution processability, spectral tunability, and compatibility with silicon-based platforms. Conventional-CQDs based on Pb, Hg, and Cd exhibit excellent performance, but pose usage/disposal challenges in everyday life as well as serious environmental and health risks. At this critical juncture, binary (Ag<sub>2</sub>X; X = S, Se, Te) and ternary (AgBiX<sub>2</sub>) silver chalcogenide CQDs have gained attention as RoHS-compliant substitutes. For near-to-mid IR detection, silver chalcogenide CQDs offer tunable bandgaps with strong absorption coefficients and favorable optoelectronic characteristics. Review highlights advance in Ag<sub>2</sub>X and AgMX<sub>2</sub> CQDs IR photodetectors, examining their integration into photodetectors device-architecture based on their optoelectronic properties. Role of controlled stoichiometry, surface passivation, and interface-engineering in enhancing photodetector performance is emphasized. With global market for CQDs IR photodetectors projected to achieve milestones, this work presents thorough overview of CQD IR photodetectors, encompassing recent advancements, prevailing challenges, and prospective directions for future development.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102956"},"PeriodicalIF":10.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734045","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
Two-step screening of lipid-polymer nanoparticles for efficient mRNA vaccine delivery and cancer immunotherapy 两步筛选用于有效mRNA疫苗递送和癌症免疫治疗的脂质聚合物纳米颗粒
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-06 DOI: 10.1016/j.nantod.2025.102943
Mengwen Huang , Chuhao Wang , Xiaojuan Wang , Dandan Chen , Jin Ling , Yue Yu , Miaomiao Zhang , Yucai Wang , Congfei Xu , Song Shen , Xianzhu Yang , Xiaojiao Du , Jun Wang
Messenger RNA (mRNA) vaccine is undoubtedly a medical breakthrough in drug development, however, its clinical application remains limited by inefficient delivery to target tissues and cells. In this study, we proposed a two-step screening strategy to optimize in vivo mRNA delivery system. First, we used the clinically approved cationic lipid, ionizable lipid and amphiphilic polymer to construct an initial library of lipid-polymer particles (LPP) with 60 various formulations for in vivo evaluation of their transfection efficiencies. Based on the results, we further constructed another library of 15 formulations to screen more effective LPPs. Then, the optimized LPP was selected and proved to be capable of effectively delivering mRNA to antigen-presenting cells (APCs), activating immune effector cells to trigger Th1/Th2 immune response, and promoting the formation of antigen-specific immune memory T cells. More importantly, LPP loaded with mRNA vaccine exhibited potent antitumor effects in both B16F10-OVA tumor model and human papillomavirus (HPV)-related TC-1 tumor model, exhibited comparable therapeutic activity to that of lipid nanoparticles (LNP) following intravenous injection. This study provides an innovative paradigm for the development of efficient mRNA delivery systems with high efficacy, safety, and clinical translation potential.
信使RNA (mRNA)疫苗无疑是药物开发的医学突破,但其临床应用仍然受到靶向组织和细胞递送效率低下的限制。在这项研究中,我们提出了一个两步筛选策略来优化mRNA在体内的传递系统。首先,我们使用临床批准的阳离子脂质、可电离脂质和两亲性聚合物构建了一个具有60种不同配方的脂质-聚合物颗粒(LPP)的初始文库,以在体内评估其转染效率。在此基础上,我们进一步构建了另一个包含15个配方的库,以筛选更有效的LPPs。然后,选择优化后的LPP并证明其能够有效地将mRNA传递给抗原提呈细胞(APCs),激活免疫效应细胞触发Th1/Th2免疫应答,促进抗原特异性免疫记忆T细胞的形成。更重要的是,负载mRNA疫苗的LPP在B16F10-OVA肿瘤模型和人乳头瘤病毒(HPV)相关TC-1肿瘤模型中均表现出强大的抗肿瘤作用,其治疗活性与静脉注射脂质纳米颗粒(LNP)相当。这项研究为开发高效、安全和具有临床翻译潜力的mRNA传递系统提供了一个创新的范例。
{"title":"Two-step screening of lipid-polymer nanoparticles for efficient mRNA vaccine delivery and cancer immunotherapy","authors":"Mengwen Huang ,&nbsp;Chuhao Wang ,&nbsp;Xiaojuan Wang ,&nbsp;Dandan Chen ,&nbsp;Jin Ling ,&nbsp;Yue Yu ,&nbsp;Miaomiao Zhang ,&nbsp;Yucai Wang ,&nbsp;Congfei Xu ,&nbsp;Song Shen ,&nbsp;Xianzhu Yang ,&nbsp;Xiaojiao Du ,&nbsp;Jun Wang","doi":"10.1016/j.nantod.2025.102943","DOIUrl":"10.1016/j.nantod.2025.102943","url":null,"abstract":"<div><div>Messenger RNA (mRNA) vaccine is undoubtedly a medical breakthrough in drug development, however, its clinical application remains limited by inefficient delivery to target tissues and cells. In this study, we proposed a two-step screening strategy to optimize in vivo mRNA delivery system. First, we used the clinically approved cationic lipid, ionizable lipid and amphiphilic polymer to construct an initial library of lipid-polymer particles (LPP) with 60 various formulations for in vivo evaluation of their transfection efficiencies. Based on the results, we further constructed another library of 15 formulations to screen more effective LPPs. Then, the optimized LPP was selected and proved to be capable of effectively delivering mRNA to antigen-presenting cells (APCs), activating immune effector cells to trigger Th1/Th2 immune response, and promoting the formation of antigen-specific immune memory T cells. More importantly, LPP loaded with mRNA vaccine exhibited potent antitumor effects in both B16F10-OVA tumor model and human papillomavirus (HPV)-related TC-1 tumor model, exhibited comparable therapeutic activity to that of lipid nanoparticles (LNP) following intravenous injection. This study provides an innovative paradigm for the development of efficient mRNA delivery systems with high efficacy, safety, and clinical translation potential.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102943"},"PeriodicalIF":10.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682142","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
Graphene-based origami with bidirectional bending and folding 基于石墨烯的双向弯曲和折叠折纸
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-12-05 DOI: 10.1016/j.nantod.2025.102955
Jiwoo Kim , Donghoon Moon , Yoona Kim , Jae Hwan Jeong , Jaehyung Yu , Jangyup Son , Arend M. van der Zande , Gwan-Hyoung Lee
The precise fabrication and deformation of three-dimensional (3D) microstructures, such as origami and kirigami with folded features typically ranging from a few to several tens of micrometers, have gained significant interest owing to their versatility in advanced microfabrication processes. However, conventional approaches relying on flexible polymers or thin metals face limitations, such as unidirectional bending and poor spatial resolution in localized deformation. Here, we present a strategy to construct graphene-based origami structures by harnessing the mechanical properties of graphene and exploiting electron beam (e-beam)–induced deformation of graphene-polymer double layer. Poly(methyl methacrylate) (PMMA)/graphene bilayer films exhibit a significant shift in the neutral axis due to the high in-plane stiffness of graphene, enabling controlled bidirectional bending under selective e-beam irradiation. By sequential e-beam exposure on PMMA-based structures with spatially patterned graphene, we achieve complex 3D geometries, including flower- and crown-like motifs, as well as folding mechanisms such as chair-like pop-up designs and box-shaped enclosures. Furthermore, we demonstrate rotational motion in wheel-shaped structures, translating out-of-plane bending into in-plane rotation by the shortening effect. Our approach expands the design freedom and functional capabilities of microfabricated systems, offering a powerful platform for programmable, reconfigurable 3D architectures in microelectromechanical systems (MEMS), robotics, and soft materials.
三维(3D)微结构的精确制造和变形,如折纸和kirigami,其折叠特征通常从几微米到几十微米不等,由于其在先进微制造工艺中的多功能性而获得了极大的兴趣。然而,依靠柔性聚合物或薄金属的传统方法面临着局限性,例如单向弯曲和局部变形的空间分辨率差。在这里,我们提出了一种利用石墨烯的力学特性和电子束诱导石墨烯-聚合物双层变形来构建基于石墨烯的折纸结构的策略。由于石墨烯的高平面内刚度,聚甲基丙烯酸甲酯(PMMA)/石墨烯双层膜在中性轴上表现出显著的位移,从而在选择性电子束照射下实现可控的双向弯曲。通过连续的电子束照射pmma结构和空间模式的石墨烯,我们实现了复杂的3D几何形状,包括花朵和皇冠状的图案,以及折叠机制,如椅子状的弹出式设计和盒状的外壳。此外,我们还演示了轮形结构中的旋转运动,通过缩短效应将面外弯曲转化为面内旋转。我们的方法扩展了微制造系统的设计自由度和功能,为微机电系统(MEMS),机器人和软材料中的可编程,可重构3D架构提供了强大的平台。
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引用次数: 0
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 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。
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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 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。
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