Biomaterials最新文献_第7页

Design and characterization of in situ cell-penetrating multi-modal gadolinium-gold nanoparticles for MR and CT imaging 用于磁共振和CT成像的原位细胞穿透多模态钆-金纳米颗粒的设计和表征

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123947

Alena Kisel , Minrui Luo , Matthew D. Bailey , Kathryn Ghobrial , Luydmila Lukashova , Yiqing Lei , T. Kevin Hitchens , Thomas J. Meade , Michel Modo

Contrast agents capable of labeling cells in situ are essential for tracking individual cells as they migrate through tissues during dynamic biological processes. Gold nanoparticles (AuNPs) conjugated with gadolinium (Gd) and fluorochromes offer multimodal detection via magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence microscopy. In this study, a systematic strategy was employed to incrementally increase the complexity of Gd-labeled AuNPs (GdAuNPs) and evaluate four distinct surface chemistries for in situ cell labeling. Comprehensive characterization of GdAuNP synthesis and stability—using inductively coupled plasma mass spectrometry, UV/visible spectroscopy, transmission electron microscopy, and MR relaxometry—demonstrated high reproducibility and a long shelf-life. Following intracerebroventricular or intrastriatal injection, histological analyses revealed that GdAuNPs labeled over 80 % of neurons in the striatum and approximately 20 % of neural stem cells (NSCs) in the subventricular zone. Only GdAuNPs functionalized with single-stranded DNA (ssDNA) were efficiently internalized by cells; GdAuNPs lacking ssDNA remained extracellular and were removed during immunohistochemical processing. ssDNA-labeled GdAuNPs localized peri-nuclearly following endocytosis. In microglia, GdAuNP also accumulated near the nucleus, whereas in macrophages, all GdAuNP formulations—including those with ssDNA—were mostly sequestered within phagosomes, indicating uptake via phagocytosis. The most effective design, termed type D GdAuNP, featured Gd chelates conjugated both to ssDNA and directly to the AuNP surface. These nanoparticles exhibited the highest MR sensitivity and contrast-to-noise ratio in MRI after in situ labeling and were also robustly detected by μCT. This stepwise approach to nanoparticle optimization demonstrates the potential to enhance multimodal imaging sensitivity, supporting the feasibility of a noninvasive visualization of in situ labeled neurons and NSCs.

造影剂能够标记细胞在原位是必要的跟踪单个细胞，因为他们在动态的生物过程中通过组织迁移。金纳米颗粒（AuNPs）与钆（Gd）和荧光染料结合，通过磁共振成像（MRI）、计算机断层扫描（CT）和荧光显微镜提供多模态检测。在这项研究中，采用了一种系统的策略来逐步增加gd标记的AuNPs （GdAuNPs）的复杂性，并评估四种不同的表面化学物质用于原位细胞标记。综合表征GdAuNP合成和稳定性-使用电感耦合等离子体质谱，紫外/可见光谱，透射电子显微镜和磁共振弛豫测量-证明了高重复性和长保质期。在脑室内或纹状体内注射后，组织学分析显示GdAuNPs标记了纹状体中80%以上的神经元和约20%的脑室下区神经干细胞（NSCs）。只有被单链DNA功能化的GdAuNPs才能被细胞有效地内化；缺乏ssDNA的GdAuNPs留在细胞外，并在免疫组织化学处理过程中被去除。ssdna标记的GdAuNPs在胞吞作用后定位于核周围。在小胶质细胞中，GdAuNP也在细胞核附近积累，而在巨噬细胞中，所有GdAuNP配方（包括那些含有ssdna的配方）大多被隔离在吞噬体内，表明通过吞噬作用被摄取。最有效的设计称为D型GdAuNP，其特点是Gd螯合物既与ssDNA结合，又直接与AuNP表面结合。在原位标记后，这些纳米颗粒在MRI上表现出最高的MR灵敏度和对比噪声比，并且在μCT上也具有很强的检测能力。这种逐步优化纳米颗粒的方法证明了提高多模态成像灵敏度的潜力，支持了原位标记神经元和NSCs的无创可视化的可行性。

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引用次数: 0

Bioinspired enzyme-catalytic nanoreactor enhances immunotherapy for spinal metastases by activating pyroptosis and the cGAS-STING pathway 生物激发酶催化纳米反应器通过激活焦亡和cGAS-STING途径增强脊髓转移的免疫治疗。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-05 DOI: 10.1016/j.biomaterials.2026.123990

Qiwei Yang , Minghao Li , Haoxiang Chen , Ying Li , Xinyuan Zhang , Yuan Gao , Chengyu Zhang , Jiuping Wu , Shuijun Zhang , Xinzhi Sun

Bone is one of the most common sites for tumor metastasis. The "seed-and-soil" relationship renders bone tissue a favorable microenvironment for the growth of circulating tumor cells. While immunotherapies, particularly immune checkpoint blockade (ICB), have achieved breakthroughs in primary solid tumors, bone metastases often respond poorly to ICB treatment. Herein, we developed an enzyme-loaded, self-cascading nanoreactor (mCL) that integrates a CaO₂ core and l-Arginine (L-Arg) with iNOS-rich macrophage membranes. This design ensures efficient tumor targeting and, upon acid-triggered decomposition, initiates a self-reinforcing cycle of Ca²⁺ overload and nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Upon targeted accumulation and penetration in tumors, CaO₂ undergoes reactive decomposition in the acidic tumor microenvironment (TME), releasing Ca²⁺, H₂O₂, and L-Arg. Subsequently, membrane derived iNOS cooperates with H₂O₂ to catalyze the conversion of L-Arg into NO, successfully overcoming the limitation of insufficient NO production within tumor cells. NO further enhances intracellular Ca²⁺ accumulation and reacts with ROS to generate highly cytotoxic RNS. These self-amplifying cascading reactions activate caspase-3/gasdermin E (GSDME)-dependent pyroptosis and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, promoting dendritic cell maturation and T cell activation, thereby remodeling the immunosuppressive TME. When used in combination with ICB, mCL significantly inhibits the growth and recurrence of hepatocellular carcinoma spinal metastasis (HCC-SM) while establishing long-lasting immune memory, providing a promising new strategy for the immunotherapy of HCC-SM.

骨是肿瘤最常见的转移部位之一。这种“种子与土壤”的关系使骨组织成为循环肿瘤细胞生长的有利微环境。虽然免疫疗法，特别是免疫检查点阻断（ICB），在原发性实体瘤中取得了突破，但骨转移瘤对ICB治疗的反应往往很差。在此，我们开发了一种酶负载的自级联纳米反应器（mCL），该反应器将CaO2核心和l-精氨酸（L-Arg）与富含inos的巨噬细胞膜结合在一起。这种设计确保了有效的肿瘤靶向，并在酸触发分解后，启动Ca2+过载和一氧化氮（NO）、活性氧（ROS）和活性氮（RNS）生成的自我强化循环。CaO2在肿瘤中靶向积累和渗透后，在酸性肿瘤微环境（TME）中进行反应性分解，释放Ca2+、H2O2和L-Arg。随后，膜源性iNOS与H2O2协同催化L-Arg转化为NO，成功克服了肿瘤细胞内NO生成不足的限制。NO进一步增强细胞内Ca2+积累，并与ROS反应产生高细胞毒性RNS。这些自扩增级联反应激活caspase-3/gasdermin E （GSDME）依赖性焦亡和环GMP-AMP合成酶刺激干扰素基因（cGAS-STING）通路，促进树突状细胞成熟和T细胞活化，从而重塑免疫抑制的TME。mCL与ICB联合使用时，可显著抑制肝癌脊柱转移（HCC-SM）的生长和复发，同时建立持久的免疫记忆，为HCC-SM的免疫治疗提供了一种有希望的新策略。

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引用次数: 0

Renal-clearable organic NIR-II dye cluster for non-invasive ureteral imaging 肾脏可清除的有机NIR-II染料簇用于无创输尿管成像

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-30 DOI: 10.1016/j.biomaterials.2025.123951

Shengjie Ma , Zimu Yuan , Chenlong Yu , Bin Sun , Ruibo Tang , Ding Zhou , Shoujun Zhu , Quan Wang

Intraoperative ureter visualization is essential in colorectal cancer (CRC) surgery, but current modalities are limited by invasiveness, poor photostability, and insufficient spatial resolution. Second near-infrared (NIR-II) fluorescence imaging provides a non-invasive approach with improved tissue penetration and spatial resolution. By modulating the aggregation behavior of NIR-II dyes, intravenous administration followed by renal metabolism enables real-time, high-resolution ureteral visualization. In this study, we prepared a series of donor–acceptor–donor-based NIR-II probes through a one-pot process where dye synthesis/PEGylation and free PEG assembly occur concurrently. The IR-FEP₁₀₀₀ cluster absorbs/emits maximally at 784/1025 nm in PBS and exhibits high photobleaching resistance due to its unique structural rigidity. Importantly, the IR-FEP₁₀₀₀ cluster exhibited renal excretion and enabled superior ureteral imaging performance with excellent biocompatibility, high resolution, and a prolonged imaging window. Furthermore, the IR-FEP₁₀₀₀ cluster enabled non-invasive, effective imaging diagnosis in scenarios of accidental ureteral transection, ligation, and clamping. Moreover, the IR-FEP₁₀₀₀ cluster combined with CO-1080 and Er-NPs enables multiplexed NIR-II imaging-guided surgery. High-contrast three-channel intraoperative imaging of the CRC peritoneal metastases, the ureters, and the intestines was provided. Multiplex NIR-II imaging enables precise tumor resection while protecting vital organs from intraoperative injury. These findings highlight that the IR-FEP₁₀₀₀ cluster exhibits advantages in non-invasive, long-duration, and high-resolution ureteral imaging with broad prospects in complex surgical scenarios.

术中输尿管可视化在结直肠癌（CRC）手术中是必不可少的，但目前的方式受到侵入性、光稳定性差和空间分辨率不足的限制。第二种近红外（NIR-II）荧光成像提供了非侵入性方法，提高了组织穿透性和空间分辨率。通过调节NIR-II染料的聚集行为，静脉给药后的肾脏代谢可以实现实时、高分辨率的输尿管可视化。在这项研究中，我们通过一锅工艺制备了一系列基于供体-受体-供体的NIR-II探针，其中染料合成/聚乙二醇化和游离聚乙二醇组装同时进行。IR-FEP1000簇在PBS中在784/1025 nm处吸收/发射最大，由于其独特的结构刚性，具有较高的抗光漂白性能。重要的是，IR-FEP1000簇显示肾脏排泄，具有优异的生物相容性，高分辨率和延长的成像窗口，具有优越的输尿管成像性能。此外，IR-FEP1000集群能够在意外输尿管横断、结扎和夹紧的情况下进行无创、有效的成像诊断。此外，IR-FEP1000簇与CO-1080和Er-NPs结合可以实现多路NIR-II成像引导手术。术中提供了结直肠癌腹膜转移灶、输尿管和肠道的高对比度三通道成像。多重NIR-II成像可以精确切除肿瘤，同时保护重要器官免受术中损伤。这些发现表明IR-FEP1000簇在无创、长时间、高分辨率输尿管成像方面具有优势，在复杂手术场景中具有广阔的应用前景。

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引用次数: 0

DAT-delivered astaxanthin reprograms adipogenesis through RhoGDI1 dephosphorylation at Ser174 and RhoA/FAK/ERK1/2 cascade suppression data传递的虾青素通过RhoGDI1的Ser174去磷酸化和RhoA/FAK/ERK1/2级联抑制重编程脂肪形成

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-04 DOI: 10.1016/j.biomaterials.2026.123979

Yapeng Hou , Yanhui Zhang , Ziyu Ma , Xin Chen , Yuanmao Xiao, Yuxuan Zhong, Fanglin Wang, Hao Tong, Xiaohong Wang, Jun Fan

Adipose tissue serves as a primary approach for soft tissue defect repair, but clinical regeneration remains limited by inadequate adipogenic capacity. While astaxanthin (AST) can ameliorate adipose dysfunction, the underlying mechanisms governing its pro-adipogenic activity remain elusive. Here, we developed an AST-loaded decellularized adipose tissue (DAT) hydrogel with the aim of boosting adipogenic potential. Subcutaneous implantation of DAT-AST hydrogel into rabbit inguinal fat pad defects significantly enhanced adipogenesis and tissue restoration. In human adipose-derived stem cells (ADSCs), astaxanthin significantly promoted the adipogenic differentiation by suppressing phosphorylation of RhoGDI1 at Ser174 - a newly identified AST-binding target. RhoGDI1 knockdown abolished AST-induced lipid accumulation and disrupted RhoGDI1 related signaling axis (RhoA/FAK/ERK1/2), demonstrating that RhoGDI1 dephosphorylation is essential for AST's pro-adipogenic action. Collectively, this work reveals a targetable pathway for adipose regeneration and establishes DAT as a promising delivery platform for AST therapeutics.

脂肪组织是软组织缺损修复的主要方法，但临床再生仍然受到脂肪生成能力不足的限制。虽然虾青素（AST）可以改善脂肪功能障碍，但其促脂肪生成活性的潜在机制尚不清楚。在这里，我们开发了一种负载ast的脱细胞脂肪组织（DAT）水凝胶，目的是提高脂肪生成潜力。DAT-AST水凝胶皮下植入兔腹股沟脂肪垫缺损可显著促进脂肪生成和组织修复。在人脂肪源性干细胞（ADSCs）中，虾青素通过抑制RhoGDI1的Ser174位点磷酸化（一个新发现的ast结合靶点）显著促进成脂分化。RhoGDI1敲低可消除AST诱导的脂质积累，并破坏RhoGDI1相关信号轴（RhoA/FAK/ERK1/2），表明RhoGDI1去磷酸化对AST的促脂肪作用至关重要。总的来说，这项工作揭示了脂肪再生的可靶向途径，并建立了DAT作为AST治疗的有希望的传递平台。

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引用次数: 0

Bridging acute-chronic myocardial infarction treatment: Dual-regulating of ROS/fibrosis via microenvironment-responsive release of NO and curcumin 桥接急慢性心肌梗死治疗：通过微环境响应性释放NO和姜黄素对ROS/纤维化的双重调节

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123954

Fang Zhang , Bingbing Zhao , Keqiang Lu , Xueping Zeng , Zikun Wang , Wei Chen , Yunyun Zhou , Juanjuan Peng , Lingzhi Zhao

Oxidative stress and fibrosis are core drivers of post-myocardial infarction dysfunction. Conventional therapies predominantly address either acute oxidative damage or chronic fibrosis, lacking strategies that concurrently target the two interconnected processes. Here, a microenvironment-responsive nanomedicine delivering nitric oxide (NO) and curcumin specifically to the infarcted heart is presented (named C@Si-NM). Constructed from glutathione-sensitive cyclic nitrate-trimethylene carbonate-polyethylene glycol block copolymer micelles crosslinked with silica, the system releases both NO and the encapsulated curcumin upon encountering elevated glutathione levels at the infarction site. In cardiomyocytes, NO suppresses the opening of mitochondrial permeability transition pore, inhibiting the release of reactive oxygen species, while curcumin directly acts as an antioxidant. In fibroblasts, NO inhibits the TGF-β/Smad pathway and curcumin downregulates the production of TGF-β, jointly suppressing fibrosis. The combined nanomedicine C@Si-NM significantly improved cardiac function in a rat model of MI after four weeks of treatment, resulting in an ejection fraction of 74 %. This value approached the normal range of 81 % and was superior to the outcomes observed with NO monotherapy at 62 % or curcumin monotherapy at 63 %. This strategy effectively mitigates both oxidative damage and fibrosis, bridging the gap between acute and chronic therapeutic interventions of myocardial infarction.

氧化应激和纤维化是心肌梗死后功能障碍的核心驱动因素。传统疗法主要针对急性氧化损伤或慢性纤维化，缺乏同时针对这两个相互关联的过程的策略。本文提出了一种微环境响应纳米药物，可将一氧化氮（NO）和姜黄素特异性地递送到梗死心脏（命名为C@Si-NM）。该系统由谷胱甘肽敏感的环硝酸盐-碳酸三亚甲基-聚乙二醇嵌段共聚物胶束与二氧化硅交联而成，当在梗死部位遇到谷胱甘肽水平升高时，该系统会释放NO和被封装的姜黄素。在心肌细胞中，NO抑制线粒体通透性过渡孔的打开，抑制活性氧的释放，而姜黄素则直接起到抗氧化剂的作用。在成纤维细胞中，NO抑制TGF-β/Smad通路，姜黄素下调TGF-β的产生，共同抑制纤维化。联合纳米药物C@Si-NM在治疗四周后显著改善心肌梗死大鼠模型的心功能，导致射血分数达到74%。该值接近81%的正常范围，优于NO单药治疗的62%或姜黄素单药治疗的63%。这一策略有效地减轻了氧化损伤和纤维化，弥合了心肌梗死急性和慢性治疗干预之间的差距。

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引用次数: 0

Biomimetic and microenvironment-adaptive nanoplatform potentiates photodynamic therapy of rheumatoid arthritis via H2S-Modulated oxygen metabolism 仿生和微环境适应性纳米平台通过h2s调节氧代谢增强类风湿关节炎的光动力治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-15 DOI: 10.1016/j.biomaterials.2025.123926

Xican Zhang , Shiyu Meng , Yi Xiao , Yonghang Liu , Zhuang Tang , Ao Li , Kefan Wu , Chong Cheng , Zhengwei Mao , Hui Guo , Yi Zhun Zhu , Xiaolin Wang

Photodynamic therapy (PDT) enables the selective eradication of inflamed synovium to reverse joint destruction in rheumatoid arthritis (RA). Nonetheless, the synovial hypoxia and poor photosensitizer biodistribution in the arthritic joints profoundly restrain the clinical application of PDT. Herein, we constructed a multipronged nanosystem (MM@SC-HN) through hierarchical integration of macrophage membrane (MM) coating and hydrogen sulfide (H₂S) donor (S-propargyl-cysteine, SPRC)/photosensitizer (Chlorine 6, Ce6) co-conjugated hyaluronic acid nanogels (SC–HN) for potentiated PDT of RA. Interestingly, MM@SC-HN demonstrated preferential accumulation in the inflamed joints rather than in the major organs due to the intrinsic inflammation chemotactic capacity of the MM cloak. Moreover, SPRC undergoes pH-triggered liberation in synovial fluid to generate therapeutic H₂S, simultaneously alleviating hypoxia and amplifying Ce6-mediated PDT efficacy through mitochondrial respiration modulation. Consequently, MM@SC-HN profoundly reshaped the intricate joint microenvironment featured by inflammation, hypoxia, pannus formation, hyperplasia, and oxidative stress, which ultimately led to ameliorated paw swelling, diminished inflammation score, and enhanced joint repair in adjuvant-induced arthritis rats. In addition, MM@SC-HN exhibited desirable hemo/cyto/histological compatibility that favored clinical translation. Collectively, our study provides a smart nanoplatform for clinical RA treatment and represents a novel approach for reinforced PDT that is readily adaptable to various diseases.

光动力疗法（PDT）能够选择性根除发炎的滑膜，以逆转类风湿关节炎（RA）的关节破坏。然而，关节炎关节滑膜缺氧和光敏剂生物分布不良严重限制了PDT的临床应用。在此，我们通过巨噬细胞膜（MM）涂层和硫化氢（H2S）供体（s -丙炔半胱氨酸，SPRC）/光敏剂（氯6，Ce6）共共轭透明质酸纳米凝胶（SC-HN）的分层整合构建了一个多管齐下的纳米系统（MM@SC-HN），用于增强RA的PDT。有趣的是，MM@SC-HN表现出在发炎关节而不是主要器官的优先积累，这是由于MM斗篷固有的炎症趋化能力。此外，SPRC在滑液中通过ph触发释放产生治疗性H2S，同时缓解缺氧并通过线粒体呼吸调节放大ce6介导的PDT疗效。因此，MM@SC-HN深刻地重塑了以炎症、缺氧、赘肉形成、增生和氧化应激为特征的复杂关节微环境，最终改善了佐剂诱导的关节炎大鼠的足跖肿胀，降低了炎症评分，并增强了关节修复。此外，MM@SC-HN表现出理想的血液/细胞/组织学相容性，有利于临床翻译。总的来说，我们的研究为临床RA治疗提供了一个智能纳米平台，代表了一种易于适应各种疾病的强化PDT的新方法。

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引用次数: 0

Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I 从免疫复合体中剥离无细胞DNA对于使用DNA酶I控制炎症至关重要。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-06 DOI: 10.1016/j.biomaterials.2026.123992

Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen

Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (e.g., LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase via formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation in vitro. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.

游离DNA （cfDNA）的过度积累已被确定为自身免疫性疾病的主要致病因素。维持cfDNA稳态的循环脱氧核糖核酸酶（循环脱氧核糖核酸酶）被抑制，因此外源性dna酶被用于降解cfDNA以控制炎症。然而，在病理状态下，cfDNA与阳离子内源性肽（如LL37）形成免疫复合物（ic），不仅削弱DNase的功效，而且促进免疫细胞内化，诱导炎症反应。以LL37- dna为模型IC，我们发现LL37的占用不仅在空间上阻碍cfDNA进入催化位点，而且通过形成三元配合物（LL37- dna -DNase I）诱导dna酶失活。这种转变严重损害了富含ll37的炎症微环境中DNase I的活性。因此，我们假设肝素，一种临床批准的阴离子糖胺聚糖，可以破坏ic并释放cfdna，恢复其降解易感性。事实上，我们发现肝素和DNA酶I的结合促进了DNA降解，并抑制了ics介导的TLR9的体外激活。然而，在类风湿关节炎（RA）模型中观察到的治疗结果仍然不理想，这是由于dna酶的血浆半衰期较短。为了验证这一点，我们设计了一种能够持续释放酶的dna酶纳米颗粒（DNase@TANP）。因此，依次给药肝素和DNase@TANP（间隔30分钟）对RA模型显示协同cfDNA降解效率，有效抑制toll样受体（TLR）介导的炎症途径并改善关节炎症。该策略利用临床批准的cfDNA清除药物，为cfDNA相关自身免疫性疾病建立了一个有希望的治疗范例。

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引用次数: 0

Corrigendum to ‘Enzyme-induced in vivo assembly of gold nanoparticles for imaging-guided synergistic chemo-photothermal therapy of tumor’ [Biomaterials 223 (2019) 119460] “酶诱导的金纳米颗粒在体内组装用于成像引导的肿瘤协同化学光热治疗”的更正[生物材料223(2019)119460]。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2026-01-17 DOI: 10.1016/j.biomaterials.2025.123971

Kuikun Yang , Yijing Liu , Yin Wang , Qilong Ren , Hongyu Guo , John B. Matson , Xiaoyuan Chen , Zhihong Nie

引用次数: 0

Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis 通过转运蛋白驱动的内吞作用口服递送的基于电荷的超分子肽纳米复合物

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123903

So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park

The development of charge-based self-assembled supramolecules can provide a groundbreaking advancement in the oral delivery of nanoparticles. In this study, we developed a series of positively charged peptide-engineered bile acids (PCBs) for the first time to interact with the negatively charged semaglutide (SG), a widely used Glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity and diabetes. Among the synthesized PCBs, PCB₄ self-assembled with semaglutide via electrostatic interactions to form stable supramolecular nanoparticles, termed positively charged bile acid-saturated semaglutide (PBSG) nanocomplexes, with an average size of approximately 279 nm under aqueous conditions. These PBSG nanocomplexes demonstrated enhanced permeability and absorption through bile acid transporter-driven endocytosis in intestinal cells and tissues, inducing natural breakdown of cell membranes. Notably, PBSG nanocomplex increased the gastrointestinal (GI) permeation and oral absorption of semaglutide, improved therapeutic efficacy in a high-fat diet (HFD)-induced animal model, and inhibited bile acid transporter activity. Moreover, Oral PBSG nanocomplex treatment elevated GLP-1 expression in vivo by facilitating semaglutide delivery and modulating bile acid metabolism at the same time. The development of these novel, charge-based, self-assembling oral peptide nanocomplexes, leveraging positively charged bile acids and transporter-driven uptake, represents a significant advancement in oral nanoparticle delivery and the design of therapeutic nanomaterials.

基于电荷的自组装超分子的发展可以为口服递送纳米颗粒提供突破性的进展。在这项研究中，我们首次开发了一系列带正电荷的肽工程胆汁酸（PCBs）与带负电荷的semaglutide （SG）相互作用，semaglutide （SG）是一种广泛使用的胰高血糖素样肽-1 （GLP-1）受体激动剂，用于治疗肥胖和糖尿病。在合成的多氯联苯中，PCB4通过静电相互作用与半马鲁肽自组装形成稳定的超分子纳米颗粒，称为带正电胆汁酸饱和半马鲁肽（PBSG）纳米复合物，在水条件下平均尺寸约为279 nm。这些PBSG纳米复合物通过胆汁酸转运蛋白驱动的肠细胞和组织内吞作用，诱导细胞膜的自然分解，显示出增强的渗透性和吸收。值得注意的是，PBSG纳米复合物增加了semaglutide的胃肠道（GI）渗透和口服吸收，提高了高脂肪饮食（HFD）诱导的动物模型的治疗效果，并抑制了胆汁酸转运蛋白的活性。此外，口服PBSG纳米复合物治疗通过促进semaglutide递送和调节胆汁酸代谢同时提高GLP-1在体内的表达。这些新型的、基于电荷的、自组装的口服肽纳米复合物的开发，利用带正电荷的胆汁酸和转运蛋白驱动的摄取，代表了口服纳米颗粒递送和治疗性纳米材料设计的重大进步。

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引用次数: 0

Dual-targeting nuclear and mitochondrial DNA damage drives immunogenic activation via PANoptosis for synergistic magneto-thermodynamic-chemotherapy 双靶向核和线粒体DNA损伤通过PANoptosis驱动免疫原性激活，用于协同磁热化疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-06-01 Epub Date: 2025-12-15 DOI: 10.1016/j.biomaterials.2025.123924

Lingcheng Wu , Jiaxin Su , Youde Cao , Hui Yuan , Zuying Li , Jingwen Ren , Mingzhao Xiao , Kexiao Yu , Bing Liang

Solid tumors often evade immunotherapy due to poor drug penetration, insufficient radical accumulation, and low immunogenicity. To address this, we engineer an injectable liquid-solid phase-transition implant (Fe₃O₄/AIPH/DDP@PLGA) that mimics an “AIM2 agonist” to trigger nuclear/mitochondrial DNA dual-damage and PANoptosis for enhanced magneto-thermal dynamic immunotherapy. The gel exhibits exceptional injectability, shape adaptability, and localized retention, enabling precise intratumoral delivery while minimizing systemic toxicity. Under alternating magnetic fields (AMF), the Fe₃O₄ component generates magnetothermal effects, triggering azo bond cleavage in AIPH for controlled •C radical release and Fe²⁺-mediated Fenton reactions with tumor-overexpressed H₂O₂. In cancer therapy, cisplatin not only amplifies ROS-induced DNA damage but also, as a widely utilized chemotherapeutic agent, induces nuclear DNA (nDNA) lesions via interstrand/intrastrand crosslinking with DNA and disruption of repair mechanisms. Cytosolic dsDNA accumulation activates AIM2-PANoptosome assembly, initiating PANoptosis, engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis), that eradicates primary tumors and primes systemic immunity through dendritic cell activation and CD8⁺ T-cell recruitment. This dual-damage strategy overcomes penetration barriers and immunogenic “cold” tumor limitations, achieving robust anti-tumor efficacy in prostate cancer models. Our work not only deciphers the mechanistic interplay of Fe₃O₄/AIPH/DDP@PLGA as a biomimetic AIM2 activator but also pioneers a transformative paradigm for solid tumor immunotherapy through controlled radical amplification and PANoptosis induction.

实体瘤由于药物侵彻性差、自由基积累不足、免疫原性低，常常逃避免疫治疗。为了解决这个问题，我们设计了一种可注射的液固相变植入物（Fe3O4/AIPH/DDP@PLGA），它模仿“AIM2激动剂”触发核/线粒体DNA双重损伤和PANoptosis，以增强磁热动态免疫治疗。该凝胶具有优异的可注射性、形状适应性和局部保留能力，能够在将全身毒性降至最低的同时实现精确的肿瘤内递送。在交变磁场（AMF）下，Fe3O4组分产生磁热效应，在AIPH中触发偶氮键裂解，以控制•C自由基的释放，并与肿瘤过表达的H2O2发生Fe2+介导的Fenton反应。在癌症治疗中，顺铂不仅放大ros诱导的DNA损伤，而且作为一种广泛使用的化疗药物，通过与DNA的链间/链内交联和破坏修复机制诱导细胞核DNA （nDNA）损伤。胞质dsDNA积累激活AIM2-PANoptosome组装，启动panoptosome，参与多种细胞死亡途径（凋亡、焦亡和坏死），通过树突状细胞激活和CD8+ t细胞募集来根除原发性肿瘤并启动全身免疫。这种双重损伤策略克服了穿透障碍和免疫原性“冷”肿瘤的限制，在前列腺癌模型中获得了强大的抗肿瘤效果。我们的工作不仅解释了Fe3O4/AIPH/DDP@PLGA作为仿生AIM2激活剂的机制相互作用，而且还通过控制自由基扩增和PANoptosis诱导开创了实体肿瘤免疫治疗的变革范例。

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