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Near-infrared-triggered synergistic therapy with a Ru-based nanocomposite hydrogel for eradicating multidrug-resistant wound infections 近红外触发的协同治疗与钌基纳米复合水凝胶根除多药耐药伤口感染。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-19 DOI: 10.1039/D6TB00808A
Zehui Xiao, Bingcong Ji, Jiangli Cao, Ting Du and Xinjun Du

The increasing prevalence of antimicrobial-resistant pathogens necessitates the development of innovative treatment strategies. To address this challenge, we designed a multifunctional hydrogel (RBP) by embedding berberine-loaded, polyethylenimine-modified mesoporous ruthenium nanoparticles (BBR@Ru NPs-PEI) into a carboxymethyl chitosan network. The resulting RBP hydrogel exhibited excellent mechanical properties, a porous structure facilitating oxygen and moisture exchange, and remarkable photothermal conversion efficiency (49.03%). Under 808 nm NIR irradiation, the hydrogel generated rapid localized hyperthermia. In vitro studies demonstrated potent, broad-spectrum antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, achieving over 99.9% bacterial eradication. The bactericidal mechanism involved synergistic effects of NIR-induced hyperthermia causing membrane damage, intracellular content leakage, and reactive oxygen species (ROS) burst. Furthermore, the RBP hydrogel-NIR(+) treatment effectively disrupted pre-formed biofilms and downregulated key virulence genes. In a full-thickness MRSA-infected mouse wound model, the RBP hydrogel combined with NIR irradiation significantly accelerated wound closure, reduced bacterial load by 99.9%, and promoted a regenerative microenvironment by downregulating pro-inflammatory cytokines (IL-6, CRP) and upregulating vascular endothelial growth factor (VEGF). Comprehensive biosafety evaluations confirmed excellent biocompatibility, and hemocompatibility (hemolysis rate <3%), and no systemic toxicity. This work presents a safe and effective photothermal hydrogel platform that synergistically eliminates MRSA and promotes tissue regeneration, offering a promising therapeutic strategy for managing complex wound infections.

抗微生物药物耐药性病原体的日益流行要求制定创新的治疗策略。为了解决这一挑战,我们设计了一种多功能水凝胶(RBP),通过将含有小檗碱的聚乙烯亚胺修饰的介孔钌纳米颗粒(BBR@Ru NPs-PEI)嵌入到羧甲基壳聚糖网络中。制备的RBP水凝胶具有优异的力学性能、有利于氧和水分交换的多孔结构和显著的光热转换效率(49.03%)。在808 nm近红外照射下,水凝胶产生快速的局部热疗。体外研究表明,对耐甲氧西林金黄色葡萄球菌(MRSA)和铜绿假单胞菌具有有效的广谱抗菌活性,达到99.9%以上的细菌根除。其杀菌机制涉及nir诱导的热疗引起的膜损伤、细胞内内容物渗漏和活性氧(ROS)爆发的协同作用。此外,RBP水凝胶- nir(+)处理有效地破坏了预形成的生物膜,下调了关键的毒力基因。在mrsa感染的全层小鼠伤口模型中,RBP水凝胶联合近红外照射可显著加速伤口愈合,减少99.9%的细菌负荷,并通过下调促炎细胞因子(IL-6、CRP)和上调血管内皮生长因子(VEGF)促进再生微环境。综合生物安全性评价证实其具有良好的生物相容性和血液相容性(溶血率)
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引用次数: 0
Combined improvement of the osteogenic and anti-inflammatory activities of Sr-doped bone cement modified with carboxymethyl cellulose 羧甲基纤维素改性掺锶骨水泥成骨和抗炎活性的联合提高。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-19 DOI: 10.1039/D6TB00609D
Xiao-Dan Li, Da-Wei Yan, Hao-Hao Ren, Hai-Tao Peng, Kun Zhao, Qi-Yi Zhang and Yong-Gang Yan

Incorporating strontium into bone cement is an effective strategy for bone repair. Macrophages play an essential role during implant osseointegration. However, whether carboxymethyl cellulose (CMC)-modified Sr-doped bone cement can jointly enhance M2 polarization and osteogenic differentiation remains unknown. To further explore this hypothesis, we introduced CMC into the hydration process of calcium sulfate hemihydrate, strontium oxide, and calcium phosphate monobasic monohydrate to form biodegradable composite bone cement (CMC/SPC). The handling and physicochemical properties of CMC/SPC can be adjusted by the formulation parameters, including CMC content and the corresponding L/P ratio required for paste formation. In vitro and in vivo experiments showed that 40%CMC/SPC induced anti-inflammatory M2 macrophage phenotypes and degraded by approximately 90% in vivo within 12 weeks. 40%CMC/SPC extracts upregulated the expression of osteogenesis-related genes. Micro-CT and histological analysis revealed that 40%CMC/SPC promoted superior bone regeneration without significant systemic toxicity in vivo. Overall, the present study indicates that CMC/SPC may provide a favorable microenvironment associated with anti-inflammatory macrophage polarization and enhanced bone formation, suggesting its potential as a candidate material for bone defect reconstruction.

骨水泥中掺入锶是一种有效的骨修复策略。巨噬细胞在种植体骨整合过程中发挥重要作用。然而,羧甲基纤维素(CMC)修饰的掺锶骨水泥是否能共同增强M2极化和成骨分化尚不清楚。为了进一步探索这一假设,我们将CMC引入到半水合硫酸钙、氧化锶和一水磷酸钙的水化过程中,形成可生物降解的复合骨水泥(CMC/SPC)。CMC/SPC的处理和理化性能可以通过配方参数来调整,包括CMC含量和相应的膏体形成所需的L/P比。体外和体内实验表明,40%CMC/SPC可诱导抗炎M2巨噬细胞表型,并在12周内降解约90%。40%CMC/SPC提取物上调成骨相关基因的表达。显微ct和组织学分析显示,40%CMC/SPC促进了良好的骨再生,在体内无明显的全身毒性。总之,本研究表明CMC/SPC可能提供了一个与抗炎巨噬细胞极化和增强骨形成相关的良好微环境,表明其作为骨缺损重建的候选材料的潜力。
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引用次数: 0
A cucurbit[7]uril-based upconversion nanoplatform for targeted photodynamic drug delivery 一种基于葫芦bbbbl的上转换纳米平台,用于靶向光动力药物递送。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-18 DOI: 10.1039/D6TB00884D
Dandan He, Zongze Duan, Guizhao Shen, Ting Liu, Simin Liu and Zhiyong Zhao

Photodynamic therapy (PDT) relies on light irradiation to induce the photochemical reaction of photosensitizers to convert oxygen (O2) into highly cytotoxic reactive oxygen species (ROS). However, its therapeutic efficacy is limited by the intracellular oxygen concentration in tumor cells and the limited tissue penetration of the excitation light. Herein, we report a cucurbit[7]uril (CB[7])-mediated upconversion nanoplatform co-loaded with AS1411-C15/Hemin (AH) and the photosensitizer triphenylporphyrin derivative (TPP). Through electrostatic adsorption between upconversion nanoparticles (UCNPs) and CB[7], the co-delivery of AH and TPP is achieved via the host–guest interaction between CB[7] and adamantane (Ad). Specifically, AH can target and recognize nucleolin overexpressed on cancer cells, while acting as a horseradish peroxidase-mimicking catalyst to convert endogenous hydrogen peroxide into O2, thereby overcoming the tumor's hypoxic microenvironment. In addition, the UCNPs convert the near-infrared laser, which offers deeper tissue penetration, into short-wavelength light. This further activates TPP to transform O2 into singlet oxygen (1O2), effectively promoting cancer cell apoptosis. Experimental results demonstrate that this multifunctional upconversion nanoplatform provides an effective strategy for targeted photodynamic drug delivery.

光动力疗法(PDT)依靠光照射诱导光敏剂的光化学反应,将氧(O2)转化为高细胞毒性的活性氧(ROS)。然而,其治疗效果受到肿瘤细胞内氧浓度和激发光穿透组织的限制。在此,我们报道了一个葫芦bb[7]介导的上转换纳米平台,共负载AS1411-C15/Hemin (AH)和光敏剂三苯基卟啉衍生物(TPP)。通过上转化纳米颗粒(UCNPs)和CB[7]之间的静电吸附,CB[7]和金刚烷(Ad)之间的主客体相互作用实现AH和TPP的共同递送。具体来说,AH可以靶向和识别癌细胞上过表达的核仁蛋白,同时作为一种模拟辣根过氧化物酶的催化剂,将内源性过氧化氢转化为O2,从而克服肿瘤的缺氧微环境。此外,UCNPs将近红外激光转换成短波光,这可以提供更深的组织穿透。这进一步激活TPP将O2转化为单线态氧(1O2),有效促进癌细胞凋亡。实验结果表明,这种多功能上转换纳米平台为靶向光动力给药提供了一种有效的策略。
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引用次数: 0
S. aromaticum aqueous extract-derived carbon dots: a biosafe antibacterial nanocatalyst for water remediation 水萃取碳点:一种生物安全的水修复抗菌纳米催化剂。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-16 DOI: 10.1039/D6TB00278A
Anurag Kumar Pandey, Sayan Mukherjee, Nantu Dogra, Tapan Kumar Nath, Sagar Pal and Santanu Dhara

The development of non-toxic antibacterial nanocatalysts for water purification and wastewater treatment on the same platform opens a greener approach for energy remediation applications. Carbon dots (CDs) derived from natural precursors have gained popularity recently because of their low toxicity and appealing physicochemical features that vary depending on carbon supply pathways. A facile, cost-effective, and environmentally friendly method was used to synthesize CDs utilizing an aqueous extract of S. aromaticum (clove buds (CE)). The physicochemical characterization of produced clove extract-derived CDs (CECDs) was performed using various spectroscopy and microscopy techniques. The effect of CECD concentration on cell toxicity and hemocompatibility was investigated. Moreover ex vivo CAM assays and in vivo toxicity assessments were performed to recognize their usefulness in biological environments. The antibacterial study reveals a log kill value of 3.5 and 4.2 and a zone of inhibition value of 5.09 mm and 6.84 mm for E. coli and S. aureus bacterial strains at 1 mg mL−1 concentration, respectively. Meanwhile, at the same concentration, a study on the breakdown of methylene blue (MB) dye shows 99.9% dye decolorization in 12 min. The obtained bio-safe CECDs have shown better potential to serve as antibacterial agents for disinfectant formulations and these nanocatalysts, can be integrated into the current wastewater treatment and purification system.

在同一平台上开发用于水净化和废水处理的无毒抗菌纳米催化剂,为能源修复应用开辟了更绿色的途径。来源于天然前体的碳点(cd)由于其低毒性和吸引人的物理化学特性而受到欢迎,这些特性随着碳供应途径的不同而变化。采用一种简单、经济、环保的方法,利用丁香芽(CE)水提物合成CDs。采用不同的光谱学和显微技术对丁香提取物衍生CDs进行了理化表征。观察CECD浓度对细胞毒性和血液相容性的影响。此外,还进行了离体CAM测定和体内毒性评估,以确认其在生物环境中的有效性。抑菌实验表明,在1 mg mL-1浓度下,对大肠杆菌和金黄色葡萄球菌的对数杀伤值分别为3.5和4.2,抑制区值分别为5.09 mm和6.84 mm。同时,在相同的浓度下,对亚甲基蓝(MB)染料的分解研究表明,在12 min内染料脱色率为99.9%。所获得的生物安全CECDs在消毒剂配方中显示出更好的抗菌潜力,这些纳米催化剂可以集成到当前的废水处理和净化系统中。
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引用次数: 0
Navigating early detection and image-guided therapy in pancreatic malignancies with multifunctional fluorescent probes 多功能荧光探针在胰腺恶性肿瘤早期检测和图像引导治疗中的应用。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-15 DOI: 10.1039/D6TB00503A
Jingyun Liu, Bin Guo, Lijun Jia, Zhenlong Wang and Fu Wang

The pancreas serves essential roles in both the digestive and endocrine systems, responsible for secreting digestive enzymes that facilitate nutrient breakdown in the small intestine and releasing hormones critical to glucose homeostasis. Structural or functional impairment of the pancreas can therefore lead to severe systemic consequences. Fluorescent probes have emerged as promising tools for early disease detection and targeted therapeutic interventions. However, pancreatic imaging poses unique challenges including deep retroperitoneal location, dense fibrotic stroma, and poor probe delivery efficiency. This review synthesizes recent advances in the development and application of fluorescent probes for pancreatic diseases, offering a systematic analysis of their structural design, sensing mechanisms, performance metrics, and comparative advantages. We also examine the translational potential of novel probe technologies—such as nanoprobes and multimodal imaging agents—in clinical practice, highlighting key directions for future research. It is anticipated that this review will serve as a valuable resource for researchers and clinicians engaged in the application of fluorescent probes for pancreatic disease diagnosis and treatment.

胰腺在消化和内分泌系统中都扮演着重要的角色,负责分泌消化酶,促进小肠营养物质的分解,并释放对葡萄糖稳态至关重要的激素。因此,胰腺的结构或功能损害可导致严重的全身后果。荧光探针已成为早期疾病检测和靶向治疗干预的有前途的工具。然而,胰腺成像面临着独特的挑战,包括腹膜后深度定位、致密的纤维化基质和较差的探针递送效率。本文综述了胰腺疾病荧光探针的发展和应用的最新进展,系统地分析了它们的结构设计、传感机制、性能指标和比较优势。我们还研究了新型探针技术(如纳米探针和多模态显像剂)在临床实践中的转化潜力,强调了未来研究的关键方向。本综述将为荧光探针在胰腺疾病诊断和治疗中的应用的研究人员和临床医生提供宝贵的资源。
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引用次数: 0
Construction of two drug-loaded gold nanoclusters@mesoporous polydopamine nanospheres and the synergistic treatment of abdominal aortic aneurysms 两种载药金nanoclusters@mesoporous聚多巴胺纳米球的构建及对腹主动脉瘤的协同治疗。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-15 DOI: 10.1039/D6TB00744A
Wenhao Li, Weina Zhang, Qin Huang, Mengjie Xu, Dehong Wu, Qi Hu, Dianwu Wu, Guangfu Yin and Zhongbing Huang

To address the therapy need of abdominal aortic aneurysm (AAA), a targeting modified multifunctional nano-delivery system (rCT-AuM) was developed, including the Au nanorod-cluster@mesoporous polydopamine core with the c(RGDfK) targeting peptide and the active herbal ingredients tetramethylpyrazine (TMP) and cryptotanshinone (CTS). rCT AuM exhibited uniform mesopores, better NIR-II photothermal conversion (efficiency 30.6%), and NIR-II responsive drug-release behavior. In cell experiments, rCT-AuM could specifically target M1 macrophages and synthetic VSMCs, and through a photothermal chemotherapeutic synergy, effectively inhibited inflammation, modulated the cell phenotype under NIR-II, and demonstrated the potential to promote endothelial repair. In an AAA mouse model, rCT-AuM exhibited significant lesion targeting and accumulation; under NIR-II irradiation, rCT-AuM simultaneously achieved localized photothermal therapy and controlled release of TMP and CTS drugs, thereby effectively inhibiting aortic dilation, improving vascular elasticity, and restoring hemodynamic parameters. These results demonstrate that rCT-AuM can serve as a synergistic platform integrating active targeting, photothermal therapy, and chemotherapy, offering a new strategy for the precise treatment of AAA and providing novel insights for the management of aortic aneurysms.

针对腹主动脉瘤(AAA)的治疗需求,开发了一种靶向修饰的多功能纳米递送系统(rCT-AuM),该系统包括Au nanorod-cluster@mesoporous聚多巴胺内核和c(RGDfK)靶向肽,以及有效草药成分川芎嗪(TMP)和隐丹参酮(CTS)。rCT AuM具有均匀的介孔,更好的NIR-II光热转化(效率30.6%)和NIR-II响应的药物释放行为。在细胞实验中,rCT-AuM可以特异性靶向M1巨噬细胞和合成VSMCs,通过光热化疗协同作用,有效抑制炎症,调节NIR-II作用下的细胞表型,显示出促进内皮修复的潜力。在AAA小鼠模型中,rCT-AuM表现出明显的病变靶向性和蓄积性;在NIR-II照射下,rCT-AuM同时实现了局部光热治疗以及TMP和CTS药物的控释,从而有效抑制主动脉扩张,改善血管弹性,恢复血流动力学参数。这些结果表明,rCT-AuM可以作为一个整合主动靶向、光热治疗和化疗的协同平台,为AAA的精确治疗提供了新的策略,并为动脉瘤的治疗提供了新的见解。
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引用次数: 0
Evaluation of Fe-MOF/graphene nanocomposites for non-enzymatic electrochemical sensing of acetaminophen Fe-MOF/石墨烯纳米复合材料对对乙酰氨基酚非酶电化学传感的评价。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-15 DOI: 10.1039/D5TB02893K
Jithin Rafi, Thangavelu Kokulnathan, Tzyy-Jiann Wang, Murugan Velmurugan and Bernaurdshaw Neppolian

Distribution and accumulation of pharmaceuticals in the environment are of growing concern due to their persistence and potential adverse effects on human health and aquatic ecosystems. In this study, we present a straightforward synthesis strategy to fabricate an electrocatalytic nanocomposite with the iron–metal–organic framework supported on graphene sheets (Fe-MOF/GR) for non-enzymatic electrochemical detection of acetaminophen (APAP). The material characteristics of the Fe-MOF/GR nanocomposite were comprehensively analyzed using various microscopic and spectroscopic techniques. The Fe-MOF/GR-modified electrode demonstrates a 3.97-fold increase in the peak oxidation current compared to the bare electrode for APAP detection. The excellent electrocatalytic activity of the Fe-MOF/GR-based electrochemical sensor toward APAP detection can be attributed to the synergistic effects of numerous exposed electro-active sites, high electrocatalytic activity, and exceptional conductivity. Under optimal synthesis conditions, the proposed electrochemical sensor exhibits a low detection limit of 10 nM, a high sensitivity of 6.7 µM−1 cm−2, and a broad linear range of 0.05 to 105.6 µM. Besides, it showcases high selectivity (<7%), satisfactory repeatability (1.6%), and robust reproducibility (2.02%). Its practical feasibility is demonstrated through its successful application in quantifying APAP in real biological and environmental water samples, yielding satisfactory recovery values. The findings of this study suggest that the proposed electrochemical sensor is a promising candidate for practical applications in APAP detection.

药物在环境中的分布和积累日益受到关注,因为它们对人类健康和水生生态系统具有持久性和潜在的不利影响。在这项研究中,我们提出了一种简单的合成策略,制备了一种电催化纳米复合材料,该材料具有石墨烯片上支撑的铁金属有机框架(Fe-MOF/GR),用于对乙酰氨基酚(APAP)的非酶电化学检测。利用各种显微和光谱技术对Fe-MOF/GR纳米复合材料的材料特性进行了综合分析。Fe-MOF/ gr修饰电极与裸电极相比,APAP检测的峰值氧化电流增加了3.97倍。基于Fe-MOF/ gr的电化学传感器对APAP检测的优异电催化活性可归因于大量暴露的电活性位点的协同效应、高电催化活性和优异的导电性。在最佳合成条件下,该电化学传感器具有10 nM的低检出限、6.7 μ M-1 cm-2的高灵敏度和0.05 ~ 105.6 μ M的宽线性范围。此外,它显示出高选择性(
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引用次数: 0
Ultrasonic nanoreactors: porous nanomaterials as multimodal platforms for precision ultrasound-responsive therapy and sonotherapy in nanomedicine 超声纳米反应器:多孔纳米材料作为纳米医学中精密超声反应治疗和超声治疗的多模态平台。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-15 DOI: 10.1039/D6TB00612D
Zepu Chang, Jinpu Yang, Shuaidong Huo, Yu Zhou and Pengkun Zhao

Stimuli-responsive drug delivery is a refined strategy in drug delivery systems, with ultrasound (US) being a notable external stimulus. US, defined as sound waves with frequencies above 20 kHz, offers multiple advantages in biomedicine, such as minimal tissue disruption, real-time imaging, high versatility, deep-tissue penetration, and beneficial mechanical effects. Porous nanomaterials (PNs), including metal–organic frameworks (MOFs), covalent organic frameworks (COFs), and others, possess high surface area to volume ratios, controllable pore sizes, and low densities. These properties make PNs highly promising for catalysis, gas storage, and especially drug delivery. In the interdisciplinary field of nanomedicine (NM), PNs sensitive to US have drawn increasing research attention, yet reviews on PNs-mediated therapy using US are scarce. This review systematically outlines the latest progress in US-triggered controlled release of cargoes from PNs. We first enumerate the synthesis methods of PNs, then summarize US-controlled therapies based on diverse mechanisms, namely sonodynamic, sonothermal, sonomechanical, or sono-combination therapies, and finally discuss the principal challenges and future prospects of PNs-mediated US-responsive therapy and sonotherapy.

刺激反应性给药是给药系统中的一种改进策略,超声(US)是一种显著的外部刺激。US被定义为频率高于20khz的声波,在生物医学中具有多种优势,例如最小的组织破坏,实时成像,高通用性,深层组织穿透和有益的机械效应。多孔纳米材料(PNs),包括金属有机骨架(mfs)、共价有机骨架(COFs)等,具有高表面积体积比、可控孔径和低密度等特点。这些特性使得PNs在催化、气体储存,特别是药物输送方面具有很大的应用前景。在纳米医学的跨学科领域,对US敏感的PNs引起了越来越多的研究关注,但关于US介导PNs治疗的综述却很少。本综述系统地概述了由美国触发的pn货物受控释放的最新进展。我们首先列举了PNs的合成方法,然后总结了基于不同机制的us控制疗法,即声动力、声温、声力学或声联合疗法,最后讨论了PNs介导的us反应疗法和超声疗法的主要挑战和未来前景。
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引用次数: 0
GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting galnac修饰的五组分脂质纳米颗粒用于肝脏靶向递送p65 siRNA,通过NF-κB靶向减轻肝损伤中的细胞因子风暴。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-15 DOI: 10.1039/D6TB00003G
Zhijie Liang, Shaorong Li, Huali Huang, Shuying Luo, Hongmian Jiang, Lifeng Luo, Jinzhuai Li and Kun Zhao

Acute liver injury (ALI) often triggers a systemic cytokine storm, in which the NF-κB subunit p65 plays a central role in driving inflammatory progression in hepatocytes. Delivering p65 siRNA to hepatocytes can effectively inhibit cellular inflammation and apoptosis. However, siRNA is inherently unstable and lacks tissue specificity. Lipid nanoparticles (LNPs) represent a mature delivery system with inherent liver tropism, yet their targeting efficiency remains suboptimal. To enhance hepatocyte-specific delivery, we developed a galactose-N-acetylgalactosamine (GalNAc)-modified five-component LNP (G-LNP) for liver-targeted delivery of p65 siRNA. GalNAc modification enables active targeting via asialoglycoprotein receptor (ASGPR)-mediated endocytosis, thereby improving hepatic accumulation and intracellular internalization. The optimized G-LNP formulation (1% DSPE–PEG2000–GalNAc) exhibited a particle size of 87 nm, a low PDI, and high encapsulation efficiency. In vitro, G-LNP–siP65 significantly enhanced transfection efficiency in AML-12 hepatocytes in an ASGPR-dependent manner, down-regulated p65 mRNA expression, alleviated CCl4-induced oxidative stress (increased SOD and decreased MDA), and reduced pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). In vivo bioluminescence imaging confirmed superior and sustained liver accumulation of G-LNP–Luc compared to unmodified LNP. Furthermore, in a CCl4-induced ALI mouse model, the G-LNP–siP65 treatment dramatically reduced serum ALT/AST levels, restored redox balance, and suppressed hepatic NF-κB expression, leading to marked amelioration of histopathological damage. Moreover, systemic safety evaluation demonstrated negligible hemolytic activity and a favorable hematological profile, as evidenced by reduced neutrophil percentage and decreased serum CRP levels. Collectively, GalNAc-modified five-component LNPs provide a potent and safe liver-targeted platform for p65 siRNA delivery, effectively mitigating cytokine storm and liver injury via NF-κB silencing. This strategy holds promise for nucleic acid-based therapies against acute and chronic liver diseases.

急性肝损伤(ALI)经常引发全身性细胞因子风暴,其中NF-κB亚基p65在驱动肝细胞炎症进展中起核心作用。向肝细胞递送p65 siRNA可有效抑制细胞炎症和凋亡。然而,siRNA本身是不稳定的,缺乏组织特异性。脂质纳米颗粒(LNPs)是一种成熟的输送系统,具有固有的肝脏亲和性,但其靶向效率仍不理想。为了增强肝细胞特异性递送,我们开发了一种半乳糖- n -乙酰半乳糖胺(GalNAc)修饰的五组分LNP (G-LNP),用于肝脏靶向递送p65 siRNA。GalNAc修饰可以通过asialal糖蛋白受体(ASGPR)介导的内吞作用实现主动靶向,从而改善肝脏积累和细胞内内化。优化后的G-LNP配方(1% DSPE-PEG2000-GalNAc)粒径为87 nm, PDI低,包封效率高。在体外,G-LNP-siP65以asgpr依赖的方式显著提高AML-12肝细胞的转染效率,下调p65 mRNA表达,减轻ccl4诱导的氧化应激(SOD升高、MDA降低),降低促炎因子(IL-6、TNF-α和IL-1β)。体内生物发光成像证实,与未修饰的LNP相比,G-LNP-Luc具有更优越且持续的肝脏积累。此外,在ccl4诱导的ALI小鼠模型中,G-LNP-siP65治疗可显著降低血清ALT/AST水平,恢复氧化还原平衡,抑制肝脏NF-κB表达,导致组织病理学损伤明显改善。此外,系统安全性评估显示可以忽略不计的溶血活性和良好的血液学特征,如中性粒细胞百分比降低和血清CRP水平降低。总之,galnac修饰的五组分LNPs为p65 siRNA递送提供了一个有效和安全的肝脏靶向平台,通过NF-κB沉默有效减轻细胞因子风暴和肝脏损伤。这一策略为基于核酸的治疗急性和慢性肝病带来了希望。
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引用次数: 0
Lactate-sensitive nanomachines for enzyme-controlled drug delivery in cancer therapy 用于癌症治疗中酶控药物递送的乳酸敏感纳米机器。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-05-14 DOI: 10.1039/D6TB00119J
Marta González-Jiménez, Teresa Moreno, Beatriz Mayol, Esther Garcia-Díez, Soraya Salido, Alfredo Sánchez-Sánchez, Paloma Martinez-Ruiz, Narcisa Martínez-Quiles, Diana Vilela and Reynaldo Villalonga

Here, we report the preparation of a novel enzyme-powered nanomachine for a drug delivery system based on mesoporous silica nanoparticles capped with a cyclodextrin-lactate oxidase (CD-LOx) complex, which enables controlled cargo release triggered by the presence of L-lactate in the tumor microenvironment. To this end, mesoporous silica nanoparticles were functionalized with diphenylethane-1,2-dione moieties and subsequently loaded with a cargo molecule. In parallel, a CD-LOx complex was prepared to act as a capping agent through supramolecular interactions, enabling controlled release of the encapsulated molecules in response to L-lactate. These nanodevices were first evaluated using [Ru(bpy)3]Cl2, as a model cargo, to confirm the efficiency and specificity of the gating mechanism. Subsequently, the nanomachines were loaded with the anticancer drug doxorubicin and tested in cell culture experiments at a concentration of 50 µg L−1. The results showed the best therapeutic response after 24 hours of incubation in the presence of 25 mM L-lactate, confirming that lactate-triggered H2O2 generation efficiently activates the molecular gates and promotes targeted drug release within the cellular environment. This work demonstrates the development of an autonomous lactate-responsive drug delivery system that enables selective and controlled drug release in tumor environments with high L-lactate levels.

在这里,我们报道了一种新型的酶驱动纳米机器的制备,该机器用于基于环糊精-乳酸氧化酶(CD-LOx)复合物覆盖的介孔二氧化硅纳米颗粒的药物递送系统,该系统可以通过l -乳酸在肿瘤微环境中的存在来控制货物释放。为此,介孔二氧化硅纳米颗粒被二苯乙烷-1,2-二酮基团功能化,并随后装载货物分子。同时,制备了CD-LOx配合物,通过超分子相互作用作为封盖剂,使被包裹的分子在l -乳酸盐的作用下可控释放。这些纳米器件首先使用[Ru(bpy)3]Cl2作为模型货物进行评估,以确认门控机制的效率和特异性。随后,在纳米机器上装载抗癌药物阿霉素,并在浓度为50 μ g L-1的细胞培养实验中进行测试。结果显示,25 mM l -乳酸孵育24小时后,治疗效果最佳,证实乳酸触发的H2O2生成有效激活分子门,促进细胞环境内靶向药物释放。这项工作证明了自主乳酸反应药物递送系统的发展,该系统能够在高l -乳酸水平的肿瘤环境中选择性和控制药物释放。
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Journal of Materials Chemistry B
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