Materials Today Bio最新文献_第3页

Natural polysaccharide-nucleic acid nanocomplex alleviates myocardial infarction by driving chronologically programmed macrophage polarization 天然多糖核酸纳米复合物通过驱动按时间顺序编程的巨噬细胞极化减轻心肌梗死

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102831

Xiang Guo , Shaodong Zhai , Hongnv Zhang , Zhenghao Wang , Nan Hu , Ruiping Zhang

In the temporal pathological progression of myocardial infarction (MI), acute ischemic injury triggers a macrophage-dominated inflammatory response, where the early M1 phenotype polarization aids in necrotic tissue clearance. However, persistent inflammation drives a pro-fibrotic shift, leading to cardiac remodeling and heart failure, rendering single-target therapies largely ineffective in addressing the full pathological course. To address this challenge, we developed a temporally modulated nanodelivery system. This platform integrates the natural immunomodulator zymosan A (ZymA) with siRNA-21 (SiR21) through intelligent assembly, enabling dual immunoregulatory and gene-silencing functions (ZymA@SiR21). Formulation optimization of ZymA enhanced particle uniformity and surface charge density, improving electrostatic binding with the cationic polymer PDMA for efficient SiR21 loading while boosting biosafety and immune tolerance. The system is associated with the binding of mannose groups on the ZymA surface to mannose receptors to achieve macrophage-specific targeting. This nanoplatform demonstrates time-dependent therapeutic precision: (1) During acute MI, ZymA induces macrophage polarization toward the M1 phenotype, enhancing phagocytic clearance of necrotic debris; (2) In the chronic-phase, released SiR21 sustains macrophage reprogramming to reparative M2 phenotypes and inhibits fibroblast hyperactivation. This “clearance-to-repair” strategy achieved superior outcomes in animal models and no systemic immune hyperactivation. By orchestrating macrophage dynamics, the system accelerates the restoration of inflammation-repair balance post-MI, offering a paradigm-shifting approach for stage-specific cardiac therapy.

在心肌梗死（MI）的时间病理进展中，急性缺血性损伤触发巨噬细胞主导的炎症反应，其中早期M1表型极化有助于坏死组织清除。然而，持续的炎症驱动促纤维化转变，导致心脏重塑和心力衰竭，使得单靶点治疗在解决整个病理过程中基本上无效。为了解决这一挑战，我们开发了一种暂时调制的纳米递送系统。该平台通过智能组装整合天然免疫调节剂ZymA （ZymA）和siRNA-21 (SiR21)，实现免疫调节和基因沉默双重功能（ZymA@SiR21）。优化了ZymA的配方，增强了颗粒均匀性和表面电荷密度，改善了与阳离子聚合物PDMA的静电结合，从而有效地装载SiR21，同时提高了生物安全性和免疫耐受性。该系统与ZymA表面的甘露糖基团与甘露糖受体的结合有关，以实现巨噬细胞特异性靶向。该纳米平台具有时间依赖性治疗精度：(1)急性心肌梗死期间，ZymA诱导巨噬细胞向M1表型极化，增强坏死碎片的吞噬清除；(2)在慢性期，释放的SiR21维持巨噬细胞重编程至修复性M2表型，并抑制成纤维细胞过度活化。这种“清除-修复”策略在动物模型中取得了优异的结果，没有出现全身免疫过度激活。通过协调巨噬细胞动力学，该系统加速心肌梗死后炎症修复平衡的恢复，为特定阶段的心脏治疗提供了一种范式转换方法。

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引用次数: 0

Ganoderma lucidum polysaccharide-decorated extracellular vesicle enables synergistical antitumor immunotherapy 灵芝多糖修饰胞外囊泡可协同抗肿瘤免疫治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102832

Zhaorong Ouyang , Siyu Li , Ao Zhang , Shu Ye , Wanqiu Ye , Guolei Wen , Tao Wei , Biao Cai , Houli Liu

Ganoderma lucidum polysaccharide (GLP) holds considerable promise for tumor therapy, but its clinical application is limited by its poor tumor-targeting capability. Herein, we report the development of an immunoregulatory nano-bioconjugate formed by conjugating GLPs with low-pH culture medium reprogrammed CT26 tumor cell-derived extracellular vesicle (LTEV). Specifically, 4-carboxybenzeneboronic acid (CPBA), used as an intermediate coupling agent, is conjugated with the amino group of LTEV via its carboxyl group to obtain CPBA-LTEV. GLP is then covalently linked via boric ester linkages between its hydroxyl groups and the boronic acid groups of CPBA. After systemic administration, GLP@LTEV accumulates in homologous tumor tissues derived from the LTEV parent cells, remodeling the immunosuppressive tumor microenvironment (TME) by repolarizing M2-like macrophages towards the M1 phenotype, promoting dendritic cell (DC) maturation, activating cytotoxic T lymphocytes (CTLs), and inhibiting immunosuppressive regulatory T cells (Tregs). The synergism of tumor-targeting delivery and potent immunomodulatory effects in this combined manner therefore significantly inhibits subcutaneous tumor growth and lung metastasis with minimal side effects, providing a novel combination of polysaccharide and nanovesicle for robust tumor immunotherapy.

灵芝多糖（Ganoderma lucidum多糖，GLP）在肿瘤治疗中具有广阔的应用前景，但其肿瘤靶向性较差，限制了其临床应用。在此，我们报告了一种免疫调节纳米生物偶联物的发展，该偶联物通过将GLPs与低ph培养基重编程的CT26肿瘤细胞源性细胞外囊泡（LTEV）偶联而形成。具体来说，4-羧基苯硼酸（CPBA）作为中间偶联剂，通过其羧基与LTEV的氨基偶联，得到CPBA-LTEV。然后，GLP通过其羟基和CPBA的硼酸基团之间的硼酸键共价连接。系统给药后，GLP@LTEV在来自LTEV亲本细胞的同源肿瘤组织中积累，通过使m2样巨噬细胞向M1表型再极化，促进树突状细胞（DC）成熟，激活细胞毒性T淋巴细胞（ctl）和抑制免疫抑制调节性T细胞（Tregs），重塑免疫抑制肿瘤微环境（TME）。因此，通过这种联合方式，肿瘤靶向递送和有效的免疫调节作用的协同作用显著抑制皮下肿瘤生长和肺转移，副作用最小，为强大的肿瘤免疫治疗提供了多糖和纳米囊泡的新组合。

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引用次数: 0

Ultrasound-activated piezoelectric Silk-PVDF hydrogel reprograms the osteoimmune microenvironment via NRF2 signaling for accelerated bone regeneration 超声激活压电丝- pvdf水凝胶通过NRF2信号重编程骨免疫微环境，加速骨再生

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102779

Guokang Mo , Lang Qing , Cheng Zhang , Lei Huang , Hongze Yan , Shunyi Lu , Yongxin Zhang , Weisin Chen , Xingdong Xiang , Ning Wang , Guanjie Han , Yulin Li , Libo Jiang , Jian Zhang

Bone defects pose significant clinical challenges due to the limited regenerative capacity of adult bone and the shortcomings of existing biomaterials, which lack dynamic electromechanical signaling crucial for repair. Here, we present an injectable, ultrasound-responsive piezoelectric hydrogel engineered to synergize silk fibroin's (SF) structural adaptability with polyvinylidene fluoride's (PVDF) bioelectrical activity. Methacrylated silk fibroin (SM) enables rapid UV-triggered crosslinking via a cost-effective photoinitiator system, while electrospun PVDF nanofibers, cryosectioned into microscale units, confer dynamic piezoelectric responsiveness. Under ultrasound stimulation, PVDF generates localized electrical cues that transiently elevate reactive oxygen species (ROS), activating the NRF2 antioxidant pathway to resolve oxidative stress, which polarizes macrophages toward pro-regenerative M2 phenotypes, enhances osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and promotes angiogenesis in vitro. Additionally, it was also confirmed that implantation of critical-sized femoral defects in rats could facilitate bone regeneration by micro-CT and histological analysis in vivo. This platform transcends beyond passive scaffolding by recapitulating bone's electromechanical-immune axis offers a paradigm shift toward smart biomaterials for complex skeletal defects. The integration of PVDF's ultrasound-triggered piezoelectricity with SM's bioactivity establishes a multifunctional system that dynamically regulates redox homeostasis, immune modulation, and tissue remodeling, addressing unmet needs in bone tissue engineering.

由于成人骨的再生能力有限以及现有生物材料缺乏修复所需的动态机电信号，骨缺损给临床带来了重大挑战。在这里，我们提出了一种可注射的、超声响应的压电水凝胶，其工程设计可以协同丝素蛋白（SF）的结构适应性和聚偏氟乙烯（PVDF）的生物电活性。甲基丙烯酸丝素（SM）通过具有成本效益的光引发剂系统实现了紫外线触发的快速交联，而电纺丝PVDF纳米纤维，冷冻切片成微尺度单元，赋予动态压电响应性。在超声刺激下，PVDF产生局部电信号，瞬时提升活性氧（ROS），激活NRF2抗氧化途径来解决氧化应激，使巨噬细胞向促再生M2表型极化，增强脂肪源性间充质干细胞（ADSCs）的成骨分化，促进体外血管生成。此外，显微ct和体内组织学分析也证实了植入大鼠临界尺寸股骨缺损可促进骨再生。该平台超越了被动支架，通过再现骨骼的机电免疫轴，为复杂骨骼缺陷的智能生物材料提供了范式转变。PVDF的超声触发压电性与SM的生物活性相结合，建立了一个多功能系统，可以动态调节氧化还原稳态、免疫调节和组织重塑，解决了骨组织工程中未满足的需求。

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引用次数: 0

Immediate tumor killing and long-term anti-tumor immunoreaction induced by Bufalin-loaded phototherapeutic Janus membrane in CRC postoperative therapy 负载蟾毒灵光疗Janus膜在结直肠癌术后治疗中诱导的即时肿瘤杀伤和长期抗肿瘤免疫反应

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102824

Xi Yu , Yujie He , Jiani Zhong , Yue Li , Yuan Zhu , Yingying Chen , Jingbo Yin , Zeting Yuan , Peihao Yin

Colorectal cancer (CRC) management is significantly hindered by the challenges of early detection and the high rates of recurrence and metastasis following surgery. Systemic postoperative therapies are frequently compromised by adverse effects and drug resistance. To address this, we engineered a localized and combinatorial platform by integrating Bufalin (BU), a potent anti-tumor agent from traditional Chinese medicine, into citric acid-based carbon dots modified with hyaluronic acid (BU-CDs_CA-HA), which were subsequently incorporated into a Janus-structured membrane. This design enabled robust adhesion to post-resection tumor sites, ensuring sustained local drug release and spatially confined photothermal/photodynamic therapy (PTT/PDT) while effectively sparing adjacent healthy tissues from thermal damage. Upon near-infrared (NIR) irradiation, the synergistic BU-PTT/PDT action induced potent immunogenic cell death (ICD), as evidenced by the release of damage-associated molecular patterns (DAMPs), thereby initiating a systemic anti-tumor immune response. Concurrently, BU down-regulated heat shock proteins (HSPs) and HIF-1α expression, leading to the suppression of tumor PD-L1 and effectively countering immune escape. In orthotopic and metastatic CRC mouse models, this multifunctional Janus membrane system demonstrated remarkable efficacy in preventing local recurrence and distant metastasis. This outcome was attributed to the concerted effect of immediate cytotoxic ablation and the elicited durable anti-tumor immunity. Our work presents a novel biomaterial-based strategy that enhanced the efficacy and safety of postoperative CRC treatment, offering a versatile platform for site-specific combination therapy.

结直肠癌（CRC）的治疗受到早期发现的挑战和手术后高复发和转移率的严重阻碍。全身术后治疗经常受到不良反应和耐药性的影响。为了解决这个问题，我们设计了一个局部组合平台，将蟾毒灵（BU），一种来自中药的强效抗肿瘤剂，整合到透明质酸修饰的柠檬酸基碳点（BU- cdsca - ha）中，随后将其纳入janus结构膜中。这种设计能够在切除后的肿瘤部位实现强大的粘附，确保持续的局部药物释放和空间受限的光热/光动力治疗（PTT/PDT），同时有效地保护邻近的健康组织免受热损伤。在近红外（NIR）照射下，协同的BU-PTT/PDT作用诱导了有效的免疫原性细胞死亡（ICD），正如损伤相关分子模式（DAMPs）的释放所证明的那样，从而启动了系统性的抗肿瘤免疫应答。同时，BU下调热休克蛋白（HSPs）和HIF-1α的表达，从而抑制肿瘤PD-L1，有效对抗免疫逃逸。在原位和转移性CRC小鼠模型中，这种多功能Janus膜系统在预防局部复发和远处转移方面表现出显著的疗效。这一结果归因于立即细胞毒性消融和引发持久抗肿瘤免疫的协同作用。我们的工作提出了一种新的基于生物材料的策略，提高了CRC术后治疗的有效性和安全性，为部位特异性联合治疗提供了一个多功能平台。

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引用次数: 0

Copper-enriched zinc peroxides induced cuproptosis through concurrent metabolic and oxidative dysregulation for boosting immunotherapy in colorectal cancer 富铜过氧化物锌通过同步代谢和氧化失调诱导铜沉降，促进结直肠癌的免疫治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102830

Shaopeng Zhang , Shaokang Yang , Mingqi Li , Hao Zhang , Yue Cao , Shiqi Bai , Wei Li , Bin Wang , Donghao Qu , Ziqian Wang , Wanying Li , Yanxu Sun , Daguang Wang , Yinghui Wang , Hongjie Zhang

Despite the immunotherapy has achieved the progress for advanced colorectal cancer, the unsatisfactory treatment effect remains a challenge due to the deficient immune response. In this work, we constructed a tumor microenvironments (TME)-responsive biodegradable cuproptosis inducer (ZnO₂-Cu@HA, ZCH) through cation-exchange method for amplifying the immune response. Compared to free copper ions, ZCH cloud achieve the controllable release of Cu²⁺ in tumor site, trggering efficient cuproptosis but reducing the side effect of normal tissues. Furthermore, the released Zn²⁺ could also inhibit intracellular glycolysis and ATP generation, then block the ATP7B to reduce the efflux of copper ions. Meanwhile, ZCH broke intracellular redox homeostasis via the release of exogenous H₂O₂, Cu⁺-mediated Fenton-like reaction and Zn²⁺-induced endogenous mitoROS, amplifying the cuproptosis to inducing immunogenic cell death (ICD) triggered for highly efficient immunotherapy of colorectal cancer. These findings demonstrated that it is a promising strategy of inducing efficient cuproptosis by the synergistic effect of accumulation of copper ions, inhibiting glycolysis and down-regulation GSH for efficient immunotherapy of colorectal cancer.

尽管免疫疗法治疗晚期结直肠癌取得了进展，但由于免疫应答不足，治疗效果不理想仍然是一个挑战。本研究通过阳离子交换法构建了肿瘤微环境（TME）反应的可生物降解铜化诱导剂（ZnO2-Cu@HA， ZCH），以增强免疫应答。与游离铜离子相比，ZCH云在肿瘤部位实现了Cu2+的可控释放，触发高效铜沉淀，同时减少了对正常组织的副作用。此外，释放的Zn2+还可以抑制细胞内糖酵解和ATP的生成，从而阻断ATP7B，减少铜离子的外排。同时，ZCH通过外源性H2O2的释放、Cu+介导的Fenton-like反应和Zn2+诱导的内源性mitoROS，打破细胞内氧化还原稳态，放大cuprotosis，诱导免疫原性细胞死亡（immunogenic cell death， ICD），从而引发结直肠癌的高效免疫治疗。这些发现表明，通过铜离子积累、抑制糖酵解和下调谷胱甘肽的协同作用，诱导有效的铜还原是一种有效的结肠直肠癌免疫治疗策略。

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引用次数: 0

Ultrasound-responsive CPS piezoelectric hydrogel synergistically repairs annulus fibrosus defects through immune reprogramming and cell recruitment 超声响应CPS压电水凝胶通过免疫重编程和细胞募集协同修复纤维环缺损

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-19 DOI: 10.1016/j.mtbio.2026.102825

Huajun Pan , Chengzhi Liang , Shuihua Ding , Peichuan Xu , Changxiong Cai , Chongzhi Pan , Wei Xiong , Haiyan Li , Xinxin Miao , Xigao Cheng

As a globally prevalent cause of disability, lumbar disc herniation has structural disruption of the annulus fibrosus (AF) as its pathological core. To address three critical bottlenecks in AF repair—microenvironmental imbalance (excessive inflammation/oxidative stress), inadequate cellular regeneration (low cell density), and mechanical instability—this study developed an ultrasound-responsive piezoelectric hydrogel scaffold (CPS gel) composed of cerium dioxide, poly-L-lactic acid fibers, and sodium alginate. The core mechanisms include: 1) Immune Reprogramming: Ceria nanoparticles exert dual superoxide dismutase/catalase-mimetic catalytic activity to scavenge reactive oxygen species, inhibit the NF-κB signaling pathway, downregulate IKKα/IκBα phosphorylation, and thereby drive macrophage polarization toward the M2 phenotype; 2) Directed Cellular Regeneration: Ultrasound-activated piezoelectric effects from PLLA fibers facilitate cell migration and proliferation via the ITGβ1/PI3K/AKT/ERK pathway, promoting collagen secretion; 3) Mechanical Reconstruction: The sodium alginate 'egg-box' network provides physiologically matched compressive modulus, and in vivo experiments confirm the restoration of intervertebral disc compressive stiffness. Employing a triple synergistic strategy—immunomodulation, cell recruitment, and mechanical restoration—this study proposes a promising solution for structural regeneration of the annulus fibrosus.

腰椎间盘突出症是一种全球普遍存在的致残原因，其病理核心是纤维环的结构性破坏。为了解决心房纤颤修复的三个关键瓶颈——微环境失衡（过度炎症/氧化应激）、细胞再生不足（细胞密度低）和机械不稳定，本研究开发了一种由二氧化铈、聚l -乳酸纤维和海藻酸钠组成的超声响应压电水凝胶支架（CPS凝胶）。其核心机制包括：1)免疫重编程：纳米二氧化锆发挥双超氧化物歧化酶/模拟过氧化氢酶的催化活性，清除活性氧，抑制NF-κB信号通路，下调IKKα/ i -κB α磷酸化，从而驱动巨噬细胞向M2表型极化；2)定向细胞再生：超声激活PLLA纤维的压电效应通过itg - β1/PI3K/AKT/ERK通路促进细胞迁移和增殖，促进胶原分泌；3)机械重建：海藻酸钠“蛋盒”网络提供生理匹配的压缩模量，体内实验证实了椎间盘压缩刚度的恢复。采用三重协同策略-免疫调节，细胞募集和机械修复-本研究提出了一种有希望的纤维环结构再生解决方案。

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引用次数: 0

ROS-responsive transmembrane peptide-antibody conjugate eyedrops for the non-invasive treatment of choroidoretinopathy ros反应性跨膜肽抗体偶联滴眼液无创治疗脉络膜视网膜病变

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-17 DOI: 10.1016/j.mtbio.2026.102819

Lihang Qu , Tu Lu , Jun Tan , Xinzhao Chen , Tian Tian , Shixiang Liu , Yajun Gong , Zhihao Jiang , Zhonggui He , Peng Sun , Jin Sun , Xiaoli Ma , Ruidong Gu

Choroidoretinopathy is a major public health concern that causes significant vision impairment. Although therapeutic antibodies have demonstrated potential in treating these conditions, intravitreal injections remain invasive, associated with adverse effects, and require repeated traumatic administrations. Non-invasive drug delivery methods, such as eye drops, represent an ideal alternative but are limited by ocular barriers, making it difficult for drugs to effectively reach specific lesions. In this study, we introduce a novel reactive oxygen species (ROS)-responsive transmembrane peptide–antibody conjugate (PAC) designed for non-invasive, precise antibody delivery to the deep fundus region. The responsive PAC, termed trans-activator of transcription–polyethylene glycol–maleimide (TAT-MPEG)-antibody, is synthesized by linking transmembrane peptides TAT to maleimide via ROS-sensitive diselenide bonds, enabling efficient antibody conjugation. Following eye drop administration, TAT enhances ocular penetration, allowing the conjugate to traverse ocular barriers and deliver antibodies directly to the posterior segment. Moreover, the diselenide bonds facilitate antibody release in oxidative environments, ensuring targeted drug localization at disease sites. In mouse models of choroidal neovascularization and choroidal melanoma, this conjugate demonstrated significant therapeutic efficacy, highlighting its broad clinical potential for the treatment of choroidoretinopathy.

脉络膜视网膜病变是引起严重视力损害的主要公共卫生问题。尽管治疗性抗体已被证明在治疗这些疾病方面具有潜力，但玻璃体内注射仍然是侵入性的，与不良反应有关，并且需要反复创伤性给药。非侵入性给药方法，如滴眼液，是一种理想的替代方法，但受到眼屏障的限制，使得药物难以有效地到达特定病变。在这项研究中，我们介绍了一种新的活性氧（ROS）反应跨膜肽抗体偶联物（PAC），设计用于非侵入性，精确的抗体递送到深眼底区域。反应性PAC被称为转录-聚乙二醇-马来酰亚胺反式激活剂（TAT- mpeg）抗体，是通过ros敏感的二烯键将跨膜肽TAT与马来酰亚胺连接而合成的，从而实现了有效的抗体偶联。滴眼液后，TAT增强眼穿透性，允许缀合物穿过眼屏障并将抗体直接递送到后段。此外，二硒烯键促进抗体在氧化环境中的释放，确保靶向药物定位在疾病部位。在脉络膜新生血管和脉络膜黑色素瘤的小鼠模型中，该结合物显示出显著的治疗效果，突出了其治疗脉络膜视网膜病变的广泛临床潜力。

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引用次数: 0

Iron single-atom nanozyme-mediated laser interstitial thermal therapy and anti-inflammatory effect for epilepsy 铁单原子纳米酶介导的激光间质热疗法及其抗炎作用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-17 DOI: 10.1016/j.mtbio.2026.102810

Xiao-Dan Zhang , Yu Tian , Jing Ma , Wei Lei , Wei-Jie Yu , Peng-Hui Liu , Wen Huang , Wei Huang , Ren-Fu Liu , Xiang-Tao Zhang , Feng Wang , Yang Zhu , Yuan-Xiang Lin

Developing a safe and effective treatment for epilepsy (EP) necessitates a minimally invasive system capable of precisely targeting and ablating the lesion area while effectively suppressing subsequent inflammation. In this study, we present an innovative therapeutic strategy for epilepsy, leveraging iron single-atom nanozymes (Fe/SAN) in conjunction with laser interstitial thermal therapy (LITT) and their remarkable anti-inflammatory properties. This technology offers a significant advantage by enabling precise ablation of deep brain lesions and epileptic foci without the need for invasive craniotomy procedures. Notably, Fe/SAN exhibits exceptional near-infrared photothermal efficiency, which drives LITT to selectively eliminate diseased tissue. Moreover, near-infrared thermal imaging enables real-time monitoring of temperature changes in the epileptic lesion area, ensuring precise control of the therapeutic process. Additionally, Fe/SAN exhibits outstanding multienzyme-mimicking activities, which not only facilitate the precise ablation of epileptic foci but also scavenge reactive oxygen species and suppress inflammation. In kainic acid-induced epileptic mouse model, this combination effectively reduced seizure frequency and severity, improved spatial memory, and alleviated anxiety-like behaviors. This study introduces a novel “physical ablation-microenvironment regulation” strategy that achieves precise ablation of epileptic foci while modulating the local inflammatory microenvironment, thereby offering a highly promising minimally invasive treatment option for patients with drug-resistant epilepsy.

开发一种安全有效的癫痫（EP）治疗方法需要一种能够精确靶向和消融病变区域的微创系统，同时有效抑制随后的炎症。在这项研究中，我们提出了一种创新的治疗癫痫的策略，利用铁单原子纳米酶（Fe/SAN）结合激光间质热疗法（LITT）及其显著的抗炎特性。这项技术提供了一个显著的优势，可以在不需要侵入性开颅手术的情况下精确消融脑深部病变和癫痫灶。值得注意的是，Fe/SAN表现出优异的近红外光热效率，这使得LITT能够选择性地消除病变组织。此外，近红外热成像能够实时监测癫痫病变区域的温度变化，确保对治疗过程的精确控制。此外，Fe/SAN表现出出色的多酶模拟活性，不仅有助于癫痫病灶的精确消融，还能清除活性氧并抑制炎症。在凯尼克酸诱导的癫痫小鼠模型中，该组合有效降低癫痫发作频率和严重程度，改善空间记忆，减轻焦虑样行为。本研究引入了一种新的“物理消融-微环境调节”策略，在调节局部炎症微环境的同时实现癫痫病灶的精确消融，从而为耐药癫痫患者提供了一种非常有前途的微创治疗选择。

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引用次数: 0

Minimal immune response after transplantation of a cryopreserved human amniotic membrane on the ocular surface 冷冻保存的人羊膜在眼表移植后的最小免疫反应

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-17 DOI: 10.1016/j.mtbio.2026.102821

Jean-Baptiste Baudey , Lauriana Solecki , Christophe Picard , Bastien Mathéaud , Pauline Jamain , Isabelle Jollet , Lucas Hubert , Alain Coaquette , Adeline Desanlis , Xavier Lafarge , Pascal Pedini , Florelle Gindraux

Introduction

Human amniotic membrane (hAM) is considered to have low immunogenicity since Akle et al. reported no anti-HLA antibodies (Abs) in four volunteers after subcutaneous grafting of fresh hAM in 1981. But the sensitivity of the detection methods has significantly improved since then. Furthermore, hAM graft is a massive local input of allogenic HLA-G whose potential immunogenicity has never been assessed. The objective of this study was to look for the presence of anti-HLA class I, II, and anti HLA-G Abs at 1 and 3 months after hAM transplantation on the ocular surface.

Material and methods

Twenty-three patients who required a hAM graft on the ocular surface (cornea and/or conjunctiva) for any indication were enrolled in this prospective clinical study. Sera were collected on the day of transplantation and at 1- and 3-months post-transplantation (M0, M1, M3). Anti-HLA class I, and II Abs were assessed using the Luminex® Single Antigen technique. Anti HLA-G Abs were assessed using an in-house ELISA-based detection assay, derived from the Monoclonal Antibody specific Immobilization of Platelet Antigen (MAIPA) assay.

Results

Only one patient showed de novo Ab apparition after transplantation. Six patients showed a significant increase of preformed Abs MFI (>50 %) during follow up although transient in one out of six. No anti-HLA-G Abs were identified before or after hAM transplantation.

Conclusion

This is the first study to investigate anti-HLA class I, II, and anti HLA-G Abs in a clinical setting after cryopreserved hAM transplantation. The main finding of this study is the minimal humoral immune response in our patients, supporting the immunological safety of the procedure and the excellent clinical tolerance reported across various indications over decades of use.

自1981年Akle等人报道4名志愿者在新鲜羊膜皮下移植后未发现抗hla抗体（Abs）以来，人羊膜被认为具有低免疫原性。但自那时以来，检测方法的灵敏度有了显著提高。此外，hAM移植物是大量同种异体HLA-G的局部输入，其潜在的免疫原性从未被评估过。本研究的目的是寻找hAM移植后1个月和3个月眼表抗hla I类、II类和抗HLA-G抗体的存在。材料和方法本前瞻性临床研究纳入了23例因任何适应症需要在眼表（角膜和/或结膜）进行hAM移植的患者。于移植当日及移植后1、3个月（M0、M1、M3）采集血清。使用Luminex®单抗原技术检测抗hla I类和II类抗体。抗HLA-G抗体使用基于内部elisa的检测方法进行评估，该检测方法源自单克隆抗体特异性固定血小板抗原（MAIPA）检测。结果1例患者移植后出现新生Ab现象。6例患者在随访期间显示预成型抗体MFI显著增加（50%），尽管6例中有1例是短暂的。在火腿移植前后未发现抗hla - g抗体。结论：这是首次在临床环境中研究冷冻火腿移植后抗hla I类、II类和抗HLA-G抗体的研究。这项研究的主要发现是患者的体液免疫反应最小，支持该手术的免疫安全性和数十年来各种适应症的良好临床耐受性。

{"title":"Minimal immune response after transplantation of a cryopreserved human amniotic membrane on the ocular surface","authors":"Jean-Baptiste Baudey , Lauriana Solecki , Christophe Picard , Bastien Mathéaud , Pauline Jamain , Isabelle Jollet , Lucas Hubert , Alain Coaquette , Adeline Desanlis , Xavier Lafarge , Pascal Pedini , Florelle Gindraux","doi":"10.1016/j.mtbio.2026.102821","DOIUrl":"10.1016/j.mtbio.2026.102821","url":null,"abstract":"<div><h3>Introduction</h3><div>Human amniotic membrane (hAM) is considered to have low immunogenicity since Akle et al. reported no anti-HLA antibodies (Abs) in four volunteers after subcutaneous grafting of fresh hAM in 1981. But the sensitivity of the detection methods has significantly improved since then. Furthermore, hAM graft is a massive local input of allogenic HLA-G whose potential immunogenicity has never been assessed. The objective of this study was to look for the presence of anti-HLA class I, II, and anti HLA-G Abs at 1 and 3 months after hAM transplantation on the ocular surface.</div></div><div><h3>Material and methods</h3><div>Twenty-three patients who required a hAM graft on the ocular surface (cornea and/or conjunctiva) for any indication were enrolled in this prospective clinical study. Sera were collected on the day of transplantation and at 1- and 3-months post-transplantation (M0, M1, M3). Anti-HLA class I, and II Abs were assessed using the Luminex® Single Antigen technique. Anti HLA-G Abs were assessed using an in-house ELISA-based detection assay, derived from the Monoclonal Antibody specific Immobilization of Platelet Antigen (MAIPA) assay.</div></div><div><h3>Results</h3><div>Only one patient showed <em>de novo</em> Ab apparition after transplantation. Six patients showed a significant increase of preformed Abs MFI (>50 %) during follow up although transient in one out of six. No anti-HLA-G Abs were identified before or after hAM transplantation.</div></div><div><h3>Conclusion</h3><div>This is the first study to investigate anti-HLA class I, II, and anti HLA-G Abs in a clinical setting after cryopreserved hAM transplantation. The main finding of this study is the minimal humoral immune response in our patients, supporting the immunological safety of the procedure and the excellent clinical tolerance reported across various indications over decades of use.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102821"},"PeriodicalIF":10.2,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HOCl and viscosity dual-responsive fluorescent probe for accurate discrimination between early hepatocellular carcinoma and acute liver injury HOCl和黏度双响应荧光探针对早期肝癌和急性肝损伤的准确鉴别

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-16 DOI: 10.1016/j.mtbio.2026.102816

Jiakang Sun , Lidong Cao , Mengmeng Dong , Yumeng Liu , Yun Wang , Yong Zhan

The accurate differentiation between early-stage hepatocellular carcinoma (HCC) and acute liver injury (ALI) remains a critical yet unresolved challenge in clinical practice, as these conditions share overlapping symptoms and biomarkers, often leading to misdiagnosis with conventional techniques. Although fluorescent probes offer potential for high-sensitivity imaging, existing designs typically detect only a single parameter and lack subcellular targeting precision. Consequently, a methodology that simultaneously visualizes multiple pathology-specific biomarkers within a key organelle for precise discrimination is urgently needed. Here, we present a lipid droplet-targeted, dual-channel fluorescent probe, TPA-DCN-TPE, which independently monitors microenvironmental viscosity and hypochlorous acid (HOCl). This probe exhibits a remarkable 1532-fold fluorescence enhancement in response to viscosity (red channel) and a 363-fold turn-on response to HOCl (green channel). Crucially, we discovered a distinct red-to-green signal ratio that clearly discriminates HCC (high ratio) from ALI (low ratio) in vivo, ex vivo, and in tissue sections. Our work establishes a quantifiable optical criterion for differentiating these liver pathologies, thereby addressing a major diagnostic gap. We anticipate this dual-parameter imaging strategy will advance the precision diagnosis of liver diseases and provide a versatile platform for studying organelle-specific microenvironments in other metabolic and inflammatory disorders.

早期肝细胞癌（HCC）和急性肝损伤（ALI）的准确区分在临床实践中仍然是一个关键但尚未解决的挑战，因为这些疾病具有重叠的症状和生物标志物，经常导致传统技术的误诊。虽然荧光探针提供了高灵敏度成像的潜力，但现有的设计通常只检测单个参数，缺乏亚细胞靶向精度。因此，迫切需要一种在关键细胞器内同时可视化多个病理特异性生物标志物以进行精确区分的方法。在这里，我们提出了一种针对脂滴的双通道荧光探针，TPA-DCN-TPE，它可以独立监测微环境粘度和次氯酸（HOCl）。该探针对粘度（红色通道）的荧光响应增强了1532倍，对HOCl（绿色通道）的荧光响应增强了363倍。至关重要的是，我们发现了一个明显的红绿信号比，可以在体内、离体和组织切片中清楚地区分HCC（高比率）和ALI（低比率）。我们的工作建立了一个可量化的光学标准来区分这些肝脏病理，从而解决了一个主要的诊断差距。我们预计这种双参数成像策略将促进肝脏疾病的精确诊断，并为研究其他代谢和炎症疾病的细胞器特异性微环境提供一个通用平台。

{"title":"HOCl and viscosity dual-responsive fluorescent probe for accurate discrimination between early hepatocellular carcinoma and acute liver injury","authors":"Jiakang Sun , Lidong Cao , Mengmeng Dong , Yumeng Liu , Yun Wang , Yong Zhan","doi":"10.1016/j.mtbio.2026.102816","DOIUrl":"10.1016/j.mtbio.2026.102816","url":null,"abstract":"<div><div>The accurate differentiation between early-stage hepatocellular carcinoma (HCC) and acute liver injury (ALI) remains a critical yet unresolved challenge in clinical practice, as these conditions share overlapping symptoms and biomarkers, often leading to misdiagnosis with conventional techniques. Although fluorescent probes offer potential for high-sensitivity imaging, existing designs typically detect only a single parameter and lack subcellular targeting precision. Consequently, a methodology that simultaneously visualizes multiple pathology-specific biomarkers within a key organelle for precise discrimination is urgently needed. Here, we present a lipid droplet-targeted, dual-channel fluorescent probe, <strong>TPA-DCN-TPE</strong>, which independently monitors microenvironmental viscosity and hypochlorous acid (HOCl). This probe exhibits a remarkable 1532-fold fluorescence enhancement in response to viscosity (red channel) and a 363-fold turn-on response to HOCl (green channel). Crucially, we discovered a distinct red-to-green signal ratio that clearly discriminates HCC (high ratio) from ALI (low ratio) <em>in vivo</em>, <em>ex vivo</em>, and in tissue sections. Our work establishes a quantifiable optical criterion for differentiating these liver pathologies, thereby addressing a major diagnostic gap. We anticipate this dual-parameter imaging strategy will advance the precision diagnosis of liver diseases and provide a versatile platform for studying organelle-specific microenvironments in other metabolic and inflammatory disorders.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102816"},"PeriodicalIF":10.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0