Biomaterials最新文献_第9页

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 : 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。

{"title":"Renal-clearable organic NIR-II dye cluster for non-invasive ureteral imaging","authors":"Shengjie Ma , Zimu Yuan , Chenlong Yu , Bin Sun , Ruibo Tang , Ding Zhou , Shoujun Zhu , Quan Wang","doi":"10.1016/j.biomaterials.2025.123951","DOIUrl":"10.1016/j.biomaterials.2025.123951","url":null,"abstract":"<div><div>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-FEP<sub>1000</sub> cluster absorbs/emits maximally at 784/1025 nm in PBS and exhibits high photobleaching resistance due to its unique structural rigidity. Importantly, the IR-FEP<sub>1000</sub> cluster exhibited renal excretion and enabled superior ureteral imaging performance with excellent biocompatibility, high resolution, and a prolonged imaging window. Furthermore, the IR-FEP<sub>1000</sub> cluster enabled non-invasive, effective imaging diagnosis in scenarios of accidental ureteral transection, ligation, and clamping. Moreover, the IR-FEP<sub>1000</sub> 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-FEP<sub>1000</sub> cluster exhibits advantages in non-invasive, long-duration, and high-resolution ureteral imaging with broad prospects in complex surgical scenarios.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123951"},"PeriodicalIF":12.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922314","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

Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy 葛根碳点调节肠道菌群和代谢物，协同治疗糖尿病中泛器官靶向巨噬细胞极化。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123967

Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao

Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root–derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota–metabolite–macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.

2型糖尿病是一种以代谢功能障碍和慢性炎症为特征的全身性疾病，但针对这两方面的策略仍然有限。在这里，我们提出了葛根衍生的碳点（KRCDs）作为一种天然纳米材料，可以重新编程肠道微生物群-代谢物-免疫轴，以恢复系统稳态。KRCDs具有纳米级结晶度、丰富的O/N官能团和较强的抗氧化活性。在高脂肪饮食/链脲佐菌素诱导的糖尿病小鼠中，KRCDs显著降低了空腹血糖，改善了葡萄糖耐量和胰岛素敏感性，纠正了脂质谱，减少了肝脏脂肪变性，而没有可检测到的毒性。多组学分析显示，微生物多样性增加，厌氧菌等有益菌丰富，粪便代谢物重塑，吲哚-3-甲醛（I3A）显著增加。流式细胞术和免疫荧光证实，这种代谢物与脂肪组织、肠道、肾脏、肝脏和胰腺中m2样巨噬细胞极化增强相关。来自krcd治疗供体的粪便微生物群移植重现了代谢改善和全器官M2极化，证实了微生物群依赖的机制。通过建立肠道微生物-代谢物-巨噬细胞极化通路，KRCDs作为安全的植物纳米平台，同时纠正代谢和免疫失衡，为糖尿病的多靶点干预提供了一种有希望的策略。

{"title":"Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy","authors":"Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao","doi":"10.1016/j.biomaterials.2025.123967","DOIUrl":"10.1016/j.biomaterials.2025.123967","url":null,"abstract":"<div><div>Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root–derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as <em>Anaerostipes</em>, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota–metabolite–macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123967"},"PeriodicalIF":12.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909424","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

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 : 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。

{"title":"Bridging acute-chronic myocardial infarction treatment: Dual-regulating of ROS/fibrosis via microenvironment-responsive release of NO and curcumin","authors":"Fang Zhang , Bingbing Zhao , Keqiang Lu , Xueping Zeng , Zikun Wang , Wei Chen , Yunyun Zhou , Juanjuan Peng , Lingzhi Zhao","doi":"10.1016/j.biomaterials.2025.123954","DOIUrl":"10.1016/j.biomaterials.2025.123954","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123954"},"PeriodicalIF":12.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881626","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

Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers 工程生物活性纤维结构：具有短胶原微纤维的生物打印满载干细胞的胶原衍生水凝胶。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123965

Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni

Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by in situ stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.

天然水凝胶（如胶原蛋白水凝胶）在理解细胞-基质相互作用方面具有良好的潜力，并在组织工程中得到应用。然而，具有良好的可打印性、形状保持性和稳定性的生物打印细胞负载天然水凝胶仍然是一个挑战。本研究将非水溶性短型胶原I型微纤维（COL-I μFiber）与水溶性甲基丙烯酸化胶原肽（COPMA）和黄原胶（XG）共混，形成互渗透网络，并生物打印成稳定的天然来源的COPMA-μFiber-XG结构，随后进行原位干细胞增殖和分化。首先，为了提高COPMA的打印性能和力学性能，研制了一种具有快速紫外固化和自愈性能的COPMA-μFiber-XG生物墨水。包被的人间充质干细胞（hMSCs）在生物打印构建体中沿col - 1 μ纤维扩散，28天内代谢活性增加，细胞外基质和生物活性蛋白（col - 1和sclcleraxis）的产生增加。col - 1 μFibers和纤维状COPMA基质提供的内部生物物理生化信号与外源生化信号（如转化生长因子- β 3）协同作用，进一步促进干细胞分化。总体而言，生物打印纤维COPMA-μFiber-XG构建物具有生物相容性和生物活性，可支持hMSCs的增殖和分化。

{"title":"Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers","authors":"Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni","doi":"10.1016/j.biomaterials.2025.123965","DOIUrl":"10.1016/j.biomaterials.2025.123965","url":null,"abstract":"<div><div>Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by <em>in situ</em> stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123965"},"PeriodicalIF":12.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964872","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

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models 双纳米外泌体包封水凝胶促进伤口愈合跨越异种和同种异体模型

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-27 DOI: 10.1016/j.biomaterials.2025.123953

Bibi S. Subhan , Sydney E. Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani

Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel’s modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.

慢性伤口，特别是糖尿病患者，由于微血管受损和愈合延迟，构成了一个重大的临床挑战。这项研究提出了Exo-Q，一种新型的热响应性水凝胶，由工程Q蛋白纳米纤维与外泌体（一类囊泡细胞间通讯介质）共凝胶形成。Exo-Q在生理温度下从凝胶转变为粘弹性溶液，使外泌体能够在初始爆发释放后持续释放的情况下局部局部递送。在糖尿病小鼠伤口模型中，Exo-Q有效地将人骨髓多能基质细胞衍生的外泌体直接递送到伤口床，在那里它们积聚在肉芽组织的内皮细胞中，没有可检测到的全身分布。在严格和可复制的细胞培养条件下产生的外泌体始终携带富含mirna的生物大分子货物，这些mirna在血管生成相关基因中具有有效的靶标，表明它们具有治疗潜力。外用Exo-Q导致广泛的新生血管化肉芽组织，显著加速伤口愈合，达到与非糖尿病伤口相当的水平。重要的是，水凝胶的模块化设计保持了Q蛋白纳米纤维和外泌体的功能完整性，证明了与全层人体伤口的兼容性。该平台允许量身定制，以解决糖尿病伤口愈合的关键阶段，同时确保低剂量的疗效，潜在地实现患者给药治疗。通过利用先进的生物材料，Exo-Q提高了基于外泌体的糖尿病伤口干预的治疗效果，为慢性、不愈合的伤口提供了局部、非侵入性的解决方案。这种创新的水凝胶平台代表了一种模块化治疗策略，在再生医学的临床应用中具有重要的潜力。

{"title":"Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models","authors":"Bibi S. Subhan , Sydney E. Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani","doi":"10.1016/j.biomaterials.2025.123953","DOIUrl":"10.1016/j.biomaterials.2025.123953","url":null,"abstract":"<div><div>Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel’s modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123953"},"PeriodicalIF":12.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922313","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

Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment 经皮肝细胞癌的时空可控崩解注射磁性水凝胶治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123952

Bing Chen , Hanye Xing , Xingyu Liu , Jinlong Hu , Liang Dong , Xu Yan , Yonghong Song , Yang Lu

Disintegrating hydrogels offer the advantages of synergistically enhancing therapeutic efficacy in locoregional percutaneous treatment for early hepatocellular carcinoma, enabling on-demand drug delivery with reduced side effects. However, current disintegration processes suffer from limited precise control and weak tissue penetration. Herein, we constructed an injectable ferrimagnetic hydrogen bonding cross-linked hydrogel (named as FPH) as a locoregional percutaneous agent by integrating ferrimagnetic nanoparticles into a polyvinyl alcohol (PVA) crosslinked network. This hydrogel enables remote magnetothermally triggered disintegration under an alternating magnetic field (AMF), with its disintegration temperature precisely tunable by adjusting the hydrogel's solid content. Under magnetic heating effect, FPH achieved remote “gel to disintegration” behavior at a desired temperature range of around 47 °C, effectively suppressing tumor cells and minimizing harm to normal tissues. By contrast, other commonly used hydrogen-bonded network of gelatin hydrogel disintegrated below body temperature or agarose hydrogel disintegrated over 70 °C. Benefiting from magnetothermal-controlled disintegration, drug-loaded FPH exhibited an increased release efficiency from ∼8 % (without AMF) to ∼45 % (with AMF) within 1 h. Following ultrasound-guided percutaneous delivery, FPH_DOX exhibited synergistic efficacy with magnetic hyperthermia and disintegration-mediated chemotherapy in rabbit liver tumors. Additionally, FPH is fabricated using clinically approved pharmaceutical excipients, ensuring excellent biocompatibility. This strategy inspires the design of spatiotemporally controllable disintegrating hydrogels with limitless tissue penetration depth, and expands their potential in percutaneous hepatocellular carcinoma treatment.

崩解水凝胶在早期肝细胞癌局部经皮治疗中具有协同增强疗效的优势，能够按需给药，减少副作用。然而，目前的崩解过程受到有限的精确控制和弱组织渗透的影响。本文中，我们通过将铁磁纳米颗粒整合到聚乙烯醇（PVA）交联网络中，构建了一种可注射的铁磁氢键交联水凝胶（FPH）作为局部区域透皮剂。这种水凝胶可以在交变磁场（AMF）下实现远程磁热触发分解，通过调节水凝胶的固体含量，可以精确调节其分解温度。在磁加热作用下，FPH在47℃左右的理想温度范围内实现了远程“凝胶到崩解”行为，有效抑制肿瘤细胞，最大限度地减少对正常组织的伤害。相比之下，其他常用的明胶水凝胶的氢键网络在体温以下崩解，琼脂糖水凝胶在70℃以上崩解。受益于磁热控制的崩解，载药FPH在1小时内的释放效率从8%（无AMF）增加到45%（有AMF）。超声引导下经皮给药后，FPHDOX在兔肝肿瘤中表现出与磁热疗和崩解介导的化疗协同作用。此外，FPH是使用临床批准的药物辅料制造的，确保了良好的生物相容性。这一策略启发了具有无限组织穿透深度的时空可控分解水凝胶的设计，并扩大了其在经皮肝细胞癌治疗中的潜力。

{"title":"Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment","authors":"Bing Chen , Hanye Xing , Xingyu Liu , Jinlong Hu , Liang Dong , Xu Yan , Yonghong Song , Yang Lu","doi":"10.1016/j.biomaterials.2025.123952","DOIUrl":"10.1016/j.biomaterials.2025.123952","url":null,"abstract":"<div><div>Disintegrating hydrogels offer the advantages of synergistically enhancing therapeutic efficacy in locoregional percutaneous treatment for early hepatocellular carcinoma, enabling on-demand drug delivery with reduced side effects. However, current disintegration processes suffer from limited precise control and weak tissue penetration. Herein, we constructed an injectable ferrimagnetic hydrogen bonding cross-linked hydrogel (named as FPH) as a locoregional percutaneous agent by integrating ferrimagnetic nanoparticles into a polyvinyl alcohol (PVA) crosslinked network. This hydrogel enables remote magnetothermally triggered disintegration under an alternating magnetic field (AMF), with its disintegration temperature precisely tunable by adjusting the hydrogel's solid content. Under magnetic heating effect, FPH achieved remote “gel to disintegration” behavior at a desired temperature range of around 47 °C, effectively suppressing tumor cells and minimizing harm to normal tissues. By contrast, other commonly used hydrogen-bonded network of gelatin hydrogel disintegrated below body temperature or agarose hydrogel disintegrated over 70 °C. Benefiting from magnetothermal-controlled disintegration, drug-loaded FPH exhibited an increased release efficiency from ∼8 % (without AMF) to ∼45 % (with AMF) within 1 h. Following ultrasound-guided percutaneous delivery, FPH<sub>DOX</sub> exhibited synergistic efficacy with magnetic hyperthermia and disintegration-mediated chemotherapy in rabbit liver tumors. Additionally, FPH is fabricated using clinically approved pharmaceutical excipients, ensuring excellent biocompatibility. This strategy inspires the design of spatiotemporally controllable disintegrating hydrogels with limitless tissue penetration depth, and expands their potential in percutaneous hepatocellular carcinoma treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123952"},"PeriodicalIF":12.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922318","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

Ultrabirght organic nanocrystals by amphiphile-templated crystallization for high-contrast NIR-II bioimaging 通过两亲模板结晶制备高对比度NIR-II生物成像的超透光有机纳米晶体。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123949

Peng Zhao , Minghui Cao , Hao Wang , Bohan Li , Yicheng Liu , Yan Lu , Linjie Xu , Qingyu Fu , Yanxin Chen , Pengxin Liu , Xingjun Zhu , Yijun Zheng

Fluorescence imaging in the second near-infrared window (NIR-II) has emerged as a powerful, radiation-free diagnostic tool with high temporal and spatial resolution. However, the low brightness of organic fluorophores remains a major challenge for precise clinical diagnosis. To tackle this, here, we present ultrabright NIR-II nanocrystals via an amphiphile-templated crystallization strategy. Amphiphilic dispersants bearing fluorophore-mimetic hydrophobic domains provides a template for the ordered assembly of NIR-II AIEgens through specific molecular recognition, yielding well-defined crystalline architectures. This approach promotes dense molecular packing of AIEgens, effectively constraining intramolecular rotations while forming robust water-resistant interfaces that prevent dark-state formation. As a result, the nanocrystals exhibit a sevenfold improvement over amorphous systems. The ultrabright organic nanocrystals enabled high-resolution imaging for abdominal vasculature (110 μm vs. >200 μm for amorphous counterparts), and supported the first NIR-II luciferase reporter gene assay for in vivo visualization of endogenous gene expression and cellular viability. This work provides an advanced platform for designing ultrabright NIR-II nanomaterials by crystallization, with significant implications for enhanced diagnostic precision and therapeutic efficacy in image-guided biomedical applications.

荧光成像在第二近红外窗口（NIR-II）已成为一个强大的，无辐射的诊断工具，具有高的时间和空间分辨率。然而，有机荧光团的低亮度仍然是精确临床诊断的主要挑战。为了解决这个问题，在这里，我们通过两亲模板化的结晶策略提出了超亮NIR-II纳米晶体。具有模拟荧光团疏水结构域的两亲性分散剂通过特定的分子识别为NIR-II AIEgens的有序组装提供了模板，产生了明确的晶体结构。这种方法促进了AIEgens的密集分子包装，有效地限制了分子内的旋转，同时形成了坚固的防水界面，防止了暗态的形成。结果，纳米晶体表现出比非晶系统七倍的改进。这种超亮的有机纳米晶体能够对腹部血管系统进行高分辨率成像（110 μm vs. >200 μm），并支持第一个NIR-II荧光素酶报告基因检测，用于体内内源基因表达和细胞活力的可视化。本研究为超亮NIR-II纳米材料的结晶设计提供了先进的平台，对提高图像引导生物医学应用的诊断精度和治疗效果具有重要意义。

{"title":"Ultrabirght organic nanocrystals by amphiphile-templated crystallization for high-contrast NIR-II bioimaging","authors":"Peng Zhao , Minghui Cao , Hao Wang , Bohan Li , Yicheng Liu , Yan Lu , Linjie Xu , Qingyu Fu , Yanxin Chen , Pengxin Liu , Xingjun Zhu , Yijun Zheng","doi":"10.1016/j.biomaterials.2025.123949","DOIUrl":"10.1016/j.biomaterials.2025.123949","url":null,"abstract":"<div><div>Fluorescence imaging in the second near-infrared window (NIR-II) has emerged as a powerful, radiation-free diagnostic tool with high temporal and spatial resolution. However, the low brightness of organic fluorophores remains a major challenge for precise clinical diagnosis. To tackle this, here, we present ultrabright NIR-II nanocrystals via an amphiphile-templated crystallization strategy. Amphiphilic dispersants bearing fluorophore-mimetic hydrophobic domains provides a template for the ordered assembly of NIR-II AIEgens through specific molecular recognition, yielding well-defined crystalline architectures. This approach promotes dense molecular packing of AIEgens, effectively constraining intramolecular rotations while forming robust water-resistant interfaces that prevent dark-state formation. As a result, the nanocrystals exhibit a sevenfold improvement over amorphous systems. The ultrabright organic nanocrystals enabled high-resolution imaging for abdominal vasculature (110 μm <em>vs.</em> >200 μm for amorphous counterparts), and supported the first NIR-II luciferase reporter gene assay for <em>in vivo</em> visualization of endogenous gene expression and cellular viability. This work provides an advanced platform for designing ultrabright NIR-II nanomaterials by crystallization, with significant implications for enhanced diagnostic precision and therapeutic efficacy in image-guided biomedical applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123949"},"PeriodicalIF":12.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909387","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

Engineered Needlepatch for the treatment of acute kidney injury 工程针贴治疗急性肾损伤

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123936

Xingli Zhao , Xiaochen Li , Lang He , Xin Gong , Yanhong Wang , Lin Chen , Hao Tian , Yeqin Wang , Xinrong Xu , Tai Sheng , Min Liu , Junxuan Li , Di Liu , Lang Li , Wenyan Zhao , Wen Zeng

In acute kidney injury (AKI), the loss of peritubular capillaries further aggravates the disease. Cell transplantation represents an innovative precision therapeutic strategy. However, the low survival rate of transplanted cells and the low therapeutic efficiency remain challenges for clinical application. Here, we constructed a Needlepatch loaded with the nanozymes GTFG@Fe₃O₄, and attached to a 3D printed patterned cell tubular networks hydrogel patch for in situ kidney transplantation. In the early stage of AKI, the nanozymes can effectively target ATG4B protein-enriched microenvironment, preventing the infiltration of the NLRP3 inflammasome and cellular damage, relieving inflammation. During the later stage, human induced pluripotent stem cells (hiPSCs) derived podocyte-attached patterned tubular networks of endothelial cells facilitated the rebuilding of renal microvascular network, promoting regeneration. In this process, the integration of the Needlepatch with host kidney is established. This engineered kidney composite patch alleviates the damage caused by AKI in a programmed manner and demonstrates considerable therapeutic potential in promoting renal microvascular reconstruction.

在急性肾损伤（AKI）中，小管周围毛细血管的丧失进一步加重了疾病。细胞移植是一种创新的精准治疗策略。然而，移植细胞的存活率低，治疗效果低，仍然是临床应用的挑战。在这里，我们构建了一个加载纳米酶GTFG@Fe3O4的Needlepatch，并连接到3D打印的细胞管状网络水凝胶贴片上，用于原位肾移植。在AKI早期，纳米酶能有效靶向ATG4B蛋白富集的微环境，阻止NLRP3炎性体的浸润和细胞损伤，缓解炎症反应。在后期，人诱导多能干细胞（hipsc）衍生的足细胞附着的内皮细胞管状网络促进了肾微血管网络的重建，促进了再生。在此过程中，针贴与宿主肾脏的整合得以建立。这种工程肾脏复合贴片以程序化的方式减轻了AKI引起的损伤，在促进肾脏微血管重建方面显示出相当大的治疗潜力。

{"title":"Engineered Needlepatch for the treatment of acute kidney injury","authors":"Xingli Zhao , Xiaochen Li , Lang He , Xin Gong , Yanhong Wang , Lin Chen , Hao Tian , Yeqin Wang , Xinrong Xu , Tai Sheng , Min Liu , Junxuan Li , Di Liu , Lang Li , Wenyan Zhao , Wen Zeng","doi":"10.1016/j.biomaterials.2025.123936","DOIUrl":"10.1016/j.biomaterials.2025.123936","url":null,"abstract":"<div><div>In acute kidney injury (AKI), the loss of peritubular capillaries further aggravates the disease. Cell transplantation represents an innovative precision therapeutic strategy. However, the low survival rate of transplanted cells and the low therapeutic efficiency remain challenges for clinical application. Here, we constructed a Needlepatch loaded with the nanozymes GTFG@Fe<sub>3</sub>O<sub>4</sub>, and attached to a 3D printed patterned cell tubular networks hydrogel patch for <em>in situ</em> kidney transplantation. In the early stage of AKI, the nanozymes can effectively target ATG4B protein-enriched microenvironment, preventing the infiltration of the NLRP3 inflammasome and cellular damage, relieving inflammation. During the later stage, human induced pluripotent stem cells (hiPSCs) derived podocyte-attached patterned tubular networks of endothelial cells facilitated the rebuilding of renal microvascular network, promoting regeneration. In this process, the integration of the Needlepatch with host kidney is established. This engineered kidney composite patch alleviates the damage caused by AKI in a programmed manner and demonstrates considerable therapeutic potential in promoting renal microvascular reconstruction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123936"},"PeriodicalIF":12.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881569","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

Plasmon-boosted titanium nitride-based nanoplatform for synergistic photothermal-chemodynamic cancer therapy with smart degradability 等离子体增强氮化钛纳米平台的协同光热化学动力癌症治疗与智能降解。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-25 DOI: 10.1016/j.biomaterials.2025.123950

Ruiqi Yang , Zhu You , Bojun Xie , Mingyang Liu , Eva Yazmin Santiago , Lucas V. Besteiro , Yong Wang , Baojin Ma , Hong Liu , Dongling Ma

The development of multifunctional nanoplatforms offers promising strategies for advancing cancer treatment, given the generally limited efficacy of single function nanomaterial-based therapeutics. Herein, a plasmon-enhanced “sandwich-like” nanoplatform, titanium nitride@mesoporous silica-iron oxide/polyethylenimine (TiN@mSiO₂-Fe₃O₄/PEI), is designed for synergistic photothermal and chemodynamic therapy (PTT/CDT). The core comprises multiple TiN nanoparticles exhibiting strong plasmon coupling, while the mSiO₂ shell is decorated with ultrasmall, surface-exposed Fe₃O₄ nanozymes (∼3.2 nm) to facilitate catalytic reactions with tumor-associated substrates. Under near-infrared irradiation, the nanoplatform demonstrates a favorable photothermal conversion efficiency (∼39.3 %), making it well-suited for mild-temperature PTT. Meanwhile, the localized heat generated by TiN effectively enhances the catalytic activity of adjacent Fe₃O₄ nanozymes, thereby promoting hydroxyl radical production and intracellular glutathione depletion. The synergistic photothermal-catalytic interactions within TiN@mSiO₂-Fe₃O₄/PEI result in augmented therapeutic effect by combining efficient PTT with intensified CDT by in situ thermally accelerated Fenton reactions. This is evidenced by >90 % cancer cell killing efficiency in vitro and ∼96 % tumor inhibition rate in MOC1 xenograft models. Moreover, the mSiO₂ shell, with its large mesopores, exhibits pH-responsive degradability that enables controlled Fe₃O₄ release in the acidic tumor microenvironment, which in turn improves therapeutic specificity and reduces systemic toxicity. Collectively, these results demonstrate the potential of TiN@mSiO₂-Fe₃O₄/PEI as a highly effective and versatile nanoplatform for advanced cancer nanotherapy.

考虑到基于单一功能纳米材料的治疗方法通常疗效有限，多功能纳米平台的发展为推进癌症治疗提供了有希望的策略。在这里，一个等离子体增强的“三明治状”纳米平台，钛nitride@mesoporous二氧化硅氧化铁/聚乙烯亚胺（TiN@mSiO2-Fe3O4/PEI），被设计用于协同光热和化学动力治疗（PTT/CDT）。核心由多个具有强等离子体耦合的TiN纳米颗粒组成，而二氧化硅外壳则装饰有超小的表面暴露的Fe3O4纳米酶（~ 3.2 nm），以促进与肿瘤相关底物的催化反应。在近红外照射下，纳米平台显示出良好的光热转换效率（~ 39.3%），使其非常适合于温和的PTT。同时，TiN产生的局部热有效地增强了邻近Fe3O4纳米酶的催化活性，从而促进羟基自由基的产生和细胞内谷胱甘肽的消耗。TiN@mSiO2-Fe3O4/PEI内的协同光热催化相互作用通过原位热加速芬顿反应将有效的PTT与强化的CDT相结合，从而增强了治疗效果。这一点得到了证明，体外癌细胞杀伤效率为bb90 %， MOC1异种移植模型的肿瘤抑制率为~ 96 %。此外，二氧化硅外壳具有较大的介孔，具有ph响应降解性，可以在酸性肿瘤微环境中控制Fe3O4的释放，从而提高治疗特异性并降低全身毒性。总的来说，这些结果证明了TiN@mSiO2-Fe3O4/PEI作为一种高效、通用的纳米平台用于晚期癌症纳米治疗的潜力。

{"title":"Plasmon-boosted titanium nitride-based nanoplatform for synergistic photothermal-chemodynamic cancer therapy with smart degradability","authors":"Ruiqi Yang , Zhu You , Bojun Xie , Mingyang Liu , Eva Yazmin Santiago , Lucas V. Besteiro , Yong Wang , Baojin Ma , Hong Liu , Dongling Ma","doi":"10.1016/j.biomaterials.2025.123950","DOIUrl":"10.1016/j.biomaterials.2025.123950","url":null,"abstract":"<div><div>The development of multifunctional nanoplatforms offers promising strategies for advancing cancer treatment, given the generally limited efficacy of single function nanomaterial-based therapeutics. Herein, a plasmon-enhanced “sandwich-like” nanoplatform, titanium nitride@mesoporous silica-iron oxide/polyethylenimine (TiN@mSiO<sub>2</sub>-Fe<sub>3</sub>O<sub>4</sub>/PEI), is designed for synergistic photothermal and chemodynamic therapy (PTT/CDT). The core comprises multiple TiN nanoparticles exhibiting strong plasmon coupling, while the mSiO<sub>2</sub> shell is decorated with ultrasmall, surface-exposed Fe<sub>3</sub>O<sub>4</sub> nanozymes (∼3.2 nm) to facilitate catalytic reactions with tumor-associated substrates. Under near-infrared irradiation, the nanoplatform demonstrates a favorable photothermal conversion efficiency (∼39.3 %), making it well-suited for mild-temperature PTT. Meanwhile, the localized heat generated by TiN effectively enhances the catalytic activity of adjacent Fe<sub>3</sub>O<sub>4</sub> nanozymes, thereby promoting hydroxyl radical production and intracellular glutathione depletion. The synergistic photothermal-catalytic interactions within TiN@mSiO<sub>2</sub>-Fe<sub>3</sub>O<sub>4</sub>/PEI result in augmented therapeutic effect by combining efficient PTT with intensified CDT by <em>in situ</em> thermally accelerated Fenton reactions. This is evidenced by >90 % cancer cell killing efficiency <em>in vitro</em> and ∼96 % tumor inhibition rate in MOC1 xenograft models. Moreover, the mSiO<sub>2</sub> shell, with its large mesopores, exhibits pH-responsive degradability that enables controlled Fe<sub>3</sub>O<sub>4</sub> release in the acidic tumor microenvironment, which in turn improves therapeutic specificity and reduces systemic toxicity. Collectively, these results demonstrate the potential of TiN@mSiO<sub>2</sub>-Fe<sub>3</sub>O<sub>4</sub>/PEI as a highly effective and versatile nanoplatform for advanced cancer nanotherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123950"},"PeriodicalIF":12.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848582","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

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 : 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。

{"title":"Design and characterization of in situ cell-penetrating multi-modal gadolinium-gold nanoparticles for MR and CT imaging","authors":"Alena Kisel , Minrui Luo , Matthew D. Bailey , Kathryn Ghobrial , Luydmila Lukashova , Yiqing Lei , T. Kevin Hitchens , Thomas J. Meade , Michel Modo","doi":"10.1016/j.biomaterials.2025.123947","DOIUrl":"10.1016/j.biomaterials.2025.123947","url":null,"abstract":"<div><div>Contrast agents capable of labeling cells <em>in situ</em> 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 <em>in situ</em> 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 <em>in situ</em> 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 <em>in situ</em> labeled neurons and NSCs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123947"},"PeriodicalIF":12.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881563","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