Biomaterials最新文献_第8页

Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability 设计益生菌生物氢微型工厂，启动还原应激，提高肿瘤易感性。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-15 DOI: 10.1016/j.biomaterials.2024.122892

Jie Jiang , Yuhao Lu , Xinyi Zheng , Maomao Xie , Aleksandra Jauković , Meng Gao , Huizhen Zheng

Disruption of redox homeostasis profoundly affects cellular metabolism and activities. While oxidative stress is extensively studied in cancer therapies, research on reductive stress remains in its infancy. Molecular hydrogen (H₂), a well-known antioxidant, holds significant potential to induce reductive stress due to its strong antioxidative properties, making it a promising candidate for cancer therapy. However, it remains a major challenge to develop a sustainable H₂ delivery system in vivo. Herein, we designed a micro-factory by engineering a gel-based microcapsule that encapsulates Enterobacter aerogenes, a.k.a. probiotic biohydrogen microcapsules (PBMCs), enabling the sustained H₂ generation within tumor microenvironment. Notably, PBMCs effectively suppressed the proliferation of eight tumor cell lines as well as drug-resistant cancer cells. The prolonged H₂ release from PBMCs induced reductive stress, as evidenced by a significant increase in the GSH/GSSG ratio in 4T1 cells. Moreover, PBMCs displayed significant antitumor effects in breast, melanoma and liver cancer models. The inhibition of PI3K-AKT pathway and the activation of MAPK pathway were identified as key mechanisms responsible for inducing tumor cell cycle arrest and apoptosis. The PBMCs also exhibited synergistic effects in combination with chemotherapeutics, resulting in robust inhibitions of preinvasive carcinoma growth and commonly associated pulmonary metastasis. Overall, our study introduces an innovative strategy to manipulate reductive stress in the tumor microenvironment through in situ H₂ generation, thereby enhancing tumor vulnerability.

氧化还原平衡的破坏会严重影响细胞的新陈代谢和活动。虽然氧化应激在癌症治疗中被广泛研究，但还原应激的研究仍处于起步阶段。分子氢（H2）是一种众所周知的抗氧化剂，由于其强大的抗氧化特性，它在诱导还原应激方面具有很大的潜力，因此是一种很有希望的癌症治疗候选物质。然而，开发一种可持续的体内氢气输送系统仍是一项重大挑战。在这里，我们设计了一种基于凝胶的微胶囊，它能封装产气肠杆菌（又称益生菌生物氢微胶囊（PBMCs）），从而在肿瘤微环境中持续产生H2。值得注意的是，PBMCs 能有效抑制八种肿瘤细胞系以及耐药癌细胞的增殖。4T1 细胞中的 GSH/GSSG 比值显著增加，证明了 PBMCs 长期释放 H2 引发了还原应激。此外，PBMCs 还在乳腺癌、黑色素瘤和肝癌模型中显示出显著的抗肿瘤作用。抑制 PI3K-AKT 通路和激活 MAPK 通路是诱导肿瘤细胞周期停止和凋亡的关键机制。PBMCs 与化疗药物联合使用还能产生协同效应，从而有力地抑制浸润前癌细胞的生长和常见的肺转移。总之，我们的研究提出了一种创新策略，通过原位生成 H2 来操纵肿瘤微环境中的还原应激，从而增强肿瘤的脆弱性。

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引用次数: 0

Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p 缺氧尿源干细胞的外泌体通过 miR-486-5p 靶向 SERPINE1 促进糖尿病伤口愈合

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-15 DOI: 10.1016/j.biomaterials.2024.122893

Ming-Hui Fan , Xiu-Zhen Zhang , Yan-Lin Jiang , Jin-Kui Pi , Ji-Ye Zhang , Yue-Qi Zhang , Fei Xing , Hui-Qi Xie

Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant in vivo vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486–5p in H-exo inhibit SERPINE1 activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.

血管病变和损伤是糖尿病患者伤口愈合延迟的重要因素。以往的研究表明，缺氧环境可通过调节细胞间的交流和细胞行为诱导新血管的形成。在这项研究中，我们通过对尿源性干细胞（USCs）进行缺氧预处理，增强了外泌体的血管生成潜能。为了延长外泌体在伤口部位的滞留时间，我们还设计了一种新型 dECM 水凝胶，称为 SISMA，它是由猪小肠粘膜下层（SIS）改性而成的。SISMA 水凝胶具有快速可控的凝胶化动力学、良好的生物相容性和外泌体释放能力，已被证明是一种可靠的外泌体输送载体。缺氧诱导的外泌体负载水凝胶促进了内皮细胞的增殖、迁移和管道形成。更重要的是，在损伤后的早期阶段，体内血管再生显著，证明它促进了组织修复。这可能是因为 H-exo 中的 miR-486-5p 抑制了内皮细胞中 SERPINE1 的活性。此外，miRNA 测序分析表明，血管生成增强的潜在机制可能与经典 HIF-1α 信号通路的激活有关。总之，我们的研究提出了一种新的非侵入性、无细胞治疗方法，可用于加速糖尿病伤口愈合，并开发了一种实用、高效的外泌体递送平台。

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引用次数: 0

Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates 中性粒细胞在不同的粘附基质上表现出灵活的迁移策略和痕迹形成机制。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-13 DOI: 10.1016/j.biomaterials.2024.122881

Wenbo Gao , Xiaoning Zhang , Wenhui Hu , Jie Han , Xiaoheng Liu , Yan Zhang , Mian Long

Substrate anchorage is essential for cell migration, and actin polymerization at cell front and myosin contractility at cell rear are known to govern cell forward movement. Yet their differential driving strategies for neutrophil migration on distinct adhesiveness substrates and their contributions to the migration-induced trail formation remain unclear. Here we explore the morphological changes, migration dynamics, and trail formation of neutrophils on ICAM-1 and PLL substrates, with a focus on the relationships among adhesive forces, traction forces, and out-of-plane forces. Results indicate that, on ICAM-1, neutrophil migration and trail formation rely on the coordinated interactions of Arp2/3 and myosin, along with biochemical regulation (via Syk and calpain) of adhesion and de-adhesion. This pattern leads to traction forces being concentrated at relatively fewer adhesive sites, facilitating cell forward migration. On PLL, however, neutrophils primarily depend on Arp2/3-mediated actin polymerization, resulting in a broader distribution of traction forces and weaker adhesions, which allows for higher leading-edge migrating velocities. Elevated membrane tension and out-of-plane forces generated by bleb protrusions on PLL reduce the reliance on myosin-driven contraction at the trailing edge, enabling easier tail detachment through elastic recoil. This work highlights the differential impact of substrate adhesiveness on neutrophil migration and trail formation and dynamics, providing new insights into cell migration mechanisms and potential therapeutic targets for inflammatory and immune-related disorders.

基底锚定对细胞迁移至关重要，而细胞前部的肌动蛋白聚合和细胞后部的肌球蛋白收缩是细胞向前运动的主导因素。然而，它们对中性粒细胞在不同粘附性基底上迁移的不同驱动策略以及它们对迁移诱导的痕迹形成的贡献仍不清楚。在此，我们探讨了中性粒细胞在 ICAM-1 和 PLL 基质上的形态变化、迁移动力学和痕迹形成，重点研究了粘附力、牵引力和平面外力之间的关系。结果表明，在 ICAM-1 上，中性粒细胞的迁移和痕迹形成依赖于 Arp2/3 和肌球蛋白的协调相互作用，以及粘附和去粘附的生化调控（通过 Syk 和 calpain）。这种模式导致牵引力集中在相对较少的粘附点，有利于细胞向前迁移。然而，在 PLL 上，中性粒细胞主要依赖 Arp2/3 介导的肌动蛋白聚合，导致牵引力分布更广，粘附力更弱，从而使前缘迁移速度更高。膜张力的升高和蚕泡突起对 PLL 产生的平面外力减少了后缘对肌球蛋白驱动的收缩的依赖，使尾部更容易通过弹性反冲脱离。这项研究强调了基质粘附性对中性粒细胞迁移和尾迹形成及动力学的不同影响，为细胞迁移机制以及炎症和免疫相关疾病的潜在治疗靶点提供了新的见解。

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引用次数: 0

Engineered endothelium model enables recapitulation of vascular function and early atherosclerosis development 工程内皮模型可重现血管功能和早期动脉粥样硬化的发展过程

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-12 DOI: 10.1016/j.biomaterials.2024.122889

Avelino Dos Santos Da Costa , Kopych Vadym , Kwideok Park

Human health relies heavily on the vascular endothelium. Here, we propose a novel engineered endothelium model (EEM), which recapitulated both normal vascular function and pathology. An artificial basement membrane (aBM), where porous polyvinyl alcohol hydrogel was securely integrated with human fibroblast-derived, decellularized extracellular matrix on both sides was fabricated first and followed by endothelial cells (ECs) and pericytes (PCs) adhesion, respectively. Our EEM formed robust adherens junction (VE-cad) and built an impermeable barrier with time, along with the nitric oxide (NO) secretion. In our EEM, ECs and PCs interacted each other via aBM and led to hemoglobin alpha 1 (Hb-α1) development, which was involved in NO control and was strongly interconnected with VE-cad as well. A resilient property of EEM under inflammatory milieu was also confirmed by VE-cad and barrier recovery with time. In particular interest, foam cells formation, a hallmark of atherosclerotic initiation was successfully recapitulated in our EEM, where a series of sequential events were confirmed: human monocytes adhesion, transendothelial migration, and oxidized low-density lipoprotein uptake by macrophages. Collectively, our EEM is excellent in recapitulating not only normal endothelium but early pathologic one, thereby enabling EEM to be a physiologically relevant model for vascular study and disease modeling.

人类健康在很大程度上依赖于血管内皮。在这里，我们提出了一种新型的工程血管内皮模型（EEM），它能再现正常的血管功能和病理变化。我们首先制作了人工基底膜（aBM），将多孔聚乙烯醇水凝胶与来源于成纤维细胞的脱细胞细胞外基质牢固地结合在一起，然后分别粘附内皮细胞（EC）和周细胞（PC）。随着时间的推移，随着一氧化氮（NO）的分泌，我们的 EEM 形成了坚固的粘连接头（VE-cad），并建立了一个不透水的屏障。在我们的EEM中，EC和PC通过aBM相互作用，并导致血红蛋白α1（Hb-α1）的发育，Hb-α1参与NO的控制，并与VE-cad紧密相连。VE-cad 和屏障随时间的恢复也证实了 EEM 在炎症环境下的弹性。尤其令人感兴趣的是，我们的 EEM 成功重现了动脉粥样硬化起始阶段的标志--泡沫细胞的形成，证实了一系列连续事件：人类单核细胞粘附、跨内皮迁移和巨噬细胞摄取氧化低密度脂蛋白。总之，我们的 EEM 不仅能很好地再现正常内皮，还能再现早期病理内皮，从而使 EEM 成为血管研究和疾病建模的生理学相关模型。

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引用次数: 0

In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation 原位光交联水凝胶通过消除 ROS 和调节炎症治疗辐射引起的皮肤损伤

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-12 DOI: 10.1016/j.biomaterials.2024.122891

Jintao Shen , Wencheng Jiao , Junzhe Yang , Bo Zhuang , Shumin Du , Yanping Wu , Guiyu Huang , Yizhi Zhang , Yaxin Wang , Caixia Xu , Lina Du , Yiguang Jin

The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.

辐射诱发皮肤损伤（RSI）的临床治疗是一项重大挑战，这主要是由于过量的活性氧（ROS）和持续的炎症微环境造成的急性损伤。在这里，我们设计了一种双网络水凝胶，由 5% (w/v) Pluronic F127 二丙烯酸酯和 2% (w/v) 甲基丙烯酰透明质酸组成，称为 FH 水凝胶。为了赋予水凝胶抗氧化和抗炎特性，我们加入了 PVP 改性普鲁士蓝纳米粒子（PPBs）和白藜芦醇（Res），形成 PHF@Res 水凝胶。PHF@Res 水凝胶不仅具有多种自由基清除活性（DPPH、ABTS），还具有多种类酶活性（POD、过氧化氢酶）。同时，PHF@Res-2 水凝胶还能显著抑制细胞内的 ROS，促进成纤维细胞在高氧化应激环境下的迁移。此外，在 RSI 小鼠模型中，PHF@Res-2 水凝胶能调节炎症因子和胶原沉积，明显减少上皮增生，促进肢体再生和血管新生，加速伤口愈合，其效果优于商业抗辐射制剂康复新。PHF@Res-2 水凝胶敷料在加速 RSI 伤口愈合方面显示出巨大潜力，为临床伤口管理和再生带来了巨大希望。

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引用次数: 0

Cell calcification reverses the chemoresistance of cancer cells via the conversion of glycolipid metabolism 细胞钙化可通过糖脂代谢转换逆转癌细胞的化疗抗性。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122886

Lihong Zhang , Yandi Sun , Yindan Lin , Hanhui Li , Yuqiao Huang , Ning Tang , Xueyun Zhang , Yin Lu , Vassili A. Kovalev , Eduard V. Snezhko , Yan Luo , Ben Wang

Drug resistance is an inherent challenge during cancer chemotherapy. Cancer cells favor fatty acid metabolism through metabolic reprogramming to achieve therapeutic resistance. However, an effective approach to overcoming the switch from glycolysis-dependent to fatty acid beta-oxidation-dependent anabolic and energy metabolism remains elusive. Here, we developed a macromolecular drug (folate-polySia, FpSA) to induce the extracellular microcalcification of cervical cancer cells with cisplatin resistance. Microcalcification attenuated the uptake of fatty acids and the beta-oxidation of fatty acids by mitochondrial dysfunction but boosted the glycolysis pathway. Consequently, cotreatment with Pt and FpSA inhibited cisplatin-resistant tumor growth and improved tumor-bearing mice's survival rates, indicating that FpSA switched fatty acid metabolism to glycolysis to sensitize cisplatin-resistant cells further. Taken together, cancer cell calcification induced by FpSA provides a reprogramming metabolic strategy for the treatment of chemotherapy-resistant tumors.

抗药性是癌症化疗过程中固有的挑战。癌细胞通过新陈代谢重编程来促进脂肪酸代谢，从而实现抗药性。然而，克服从依赖糖酵解到依赖脂肪酸β-氧化的合成代谢和能量代谢转换的有效方法仍未出现。在此，我们开发了一种大分子药物（叶酸-聚矽氧烷，FpSA）来诱导顺铂耐药的宫颈癌细胞细胞外微钙化。微钙化削弱了线粒体功能障碍对脂肪酸的吸收和脂肪酸的β-氧化，但促进了糖酵解途径。因此，铂和FpSA的协同处理抑制了顺铂耐药肿瘤的生长，提高了肿瘤小鼠的存活率，这表明FpSA将脂肪酸代谢转换为糖酵解，使顺铂耐药细胞进一步敏化。综上所述，FpSA诱导的癌细胞钙化为治疗化疗耐药肿瘤提供了一种重编程代谢策略。

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引用次数: 0

Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis 具有免疫调节和血管/骨生成活性的多功能丝胶基生物矿化纳米平台可加速牙周炎患者的骨再生

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122885

Piaoye Ming , Bojiang Li , Qiumei Li , Lingling Yuan , Xueyu Jiang , Yunfei Liu , Rui Cai , Peirong Zhou , Xiaorong Lan , Gang Tao , Jingang Xiao

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

牙周炎是一种由牙菌斑引起的慢性炎症。其特点是牙周区域积累了过多的活性氧（ROS）和炎症介质。这会影响宿主细胞的功能，激活破骨细胞，破坏牙周组织。为改善过度活跃的炎症微环境和修复牙周组织而采取的局部清创或抗生素治疗等方法具有挑战性。本文报道了基于丝胶蛋白的多功能纳米平台（Se-CuSrHA@EGCG），该平台具有清除 ROS、免疫调节、血管生成和成骨功能。从蚕茧中提取的天然蛋白质丝胶在水/油乳化和交联过程中被用于制造丝胶纳米粒子（Se NPs）。Se NPs 表面有许多结合位点。离子掺杂的羟基磷灰石纳米粒子（Se-CuSrHA NPs）可利用正负电荷之间的作用力构建。矿化后，利用聚乙烯亚胺（PEI）/表没食子儿茶素没食子酸酯（EGCG）在其表面形成抗氧化涂层。体外和体内研究表明，Se-CuSrHA@EGCG NPs 能有效清除 ROS，调节巨噬细胞极化，增加抗炎细胞因子的分泌，平衡免疫微环境。此外，Se-CuSrHA@EGCG 还能刺激血管生成，抑制破骨细胞，加速牙周组织修复。因此，这是加速牙周炎患者骨再生的一种可取策略。

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引用次数: 0

An innovative strategy harnessing self-activating CAR-NK cells to mitigate TGF-β1-driven immune suppression 利用自激活 CAR-NK 细胞减轻 TGF-β1 驱动的免疫抑制的创新战略

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122888

Seung hun Shin , Young Eun Lee , Han-Na Yoon , Chae Min Yuk , Jun Yop An , Minkoo Seo , Sangwon Yoon , Min-Suk Oh , Sang Chul Shin , Ji Hyung Kim , Yong Jun Kim , Jin-Chul Kim , Song Cheol Kim , Mihue Jang

The dysfunction of natural killer (NK) cells, mediated by transforming growth factor β1 (TGFβ1) within the tumor microenvironment, impedes antitumor therapy and contributes to poor clinical outcomes. Our study introduces self-activating chimeric antigen receptor (CAR)-NK cells that block TGFβ1 signaling by releasing a specifically designed peptide, P6, which targets mesothelin in pancreatic tumors. P6 originates from the interaction sites between TGFβ1 and TGFβ receptor 1 and effectively disrupts TGFβ1's inhibitory signaling in NK cells. Our analysis demonstrates that P6 treatment interrupts the SMAD2/3 pathway in NK cells, mitigating TGFβ1-mediated suppression of NK cell activity, thereby enhancing their metabolic function and cytotoxic response against pancreatic tumors. These CAR-NK cells exhibit potent antitumor capabilities, as evidenced in spheroid cultures with cancer-associated fibroblasts and in vivo mouse models. Our approach marks a substantial advancement in overcoming TGFβ1-mediated immune evasion, offering a promising avenue for revolutionizing cancer immunotherapy.

肿瘤微环境中的转化生长因子β1（TGFβ1）介导的自然杀伤（NK）细胞功能障碍阻碍了抗肿瘤治疗，导致临床疗效不佳。我们的研究引入了自激活嵌合抗原受体（CAR）-NK细胞，这种细胞通过释放专门设计的多肽P6阻断TGFβ1信号传导，P6靶向胰腺肿瘤中的间皮素。P6源自TGFβ1和TGFβ受体1之间的相互作用位点，能有效破坏TGFβ1在NK细胞中的抑制信号传导。我们的分析表明，P6 处理能中断 NK 细胞中的 SMAD2/3 通路，减轻 TGFβ1 介导的对 NK 细胞活性的抑制，从而增强它们的代谢功能和对胰腺肿瘤的细胞毒反应。这些 CAR-NK 细胞表现出了强大的抗肿瘤能力，这一点在球状培养物与癌症相关成纤维细胞以及体内小鼠模型中都得到了证实。我们的方法标志着在克服 TGFβ1 介导的免疫逃避方面取得了重大进展，为彻底改变癌症免疫疗法提供了一条前景广阔的途径。

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引用次数: 0

Mesenchymal stromal cells surface engineering for efficient hematopoietic reconstitution 用于高效造血重建的间充质基质细胞表面工程

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122882

Huiyang Li , Lifei Ma , Ni Zhu , Xiaoyu Liang , Xinxin Tian , Kaijing Liu , Xue Fu , Xiaoli Wang , Hailing Zhang , Houzao Chen , Qiang Liu , Jing Yang

Mesenchymal stromal cells (MSCs) are believed to migrate to injury sites, release chemical attractants, and either recruit local stem cells or modulate the immune system positively. Although MSCs are highly desired for their potential to reduce inflammation and promote tissue regeneration, their limited lifespan restricts their applications. This study presents a simple approach for protecting MSCs with epigallocatechin-3-gallate (EGCG) and magnesium (Mg) based metal-organic framework coatings (E-Mg@MSC). The layer strengthens MSCs resistant to harmful stresses and creates a favorable microenvironment for repair by providing Mg to facilitate MSCs' osteogenic differentiation and using EGCG to neutralize excessive reactive oxygen species (ROS). E-Mg@MSC serves as a treatment for hematopoietic injury induced by ionizing radiation (IR). Coated MSCs exhibit sustained secretion of hematopoietic growth factors and precise homing to radiation-sensitive tissues. In vivo studies show substantial enhancement in hematopoietic system recovery and multi-organ protection. Mechanistic investigations suggest that E-Mg@MSC mitigates IR-induced ROS, cell apoptosis, and ferroptosis, contributing to reduced radiation damage. The system represents a versatile and compelling strategy for cell-surface engineering with functional materials to advance MSCs therapy.

间充质基质细胞（MSCs）被认为可迁移到损伤部位，释放化学吸引物，招募当地干细胞或积极调节免疫系统。虽然间充质干细胞因其减少炎症和促进组织再生的潜力而备受青睐，但其有限的寿命限制了其应用。本研究提出了一种利用表没食子儿茶素-3-棓酸盐（EGCG）和镁（Mg）金属有机框架涂层（E-Mg@MSC）保护间充质干细胞的简单方法。通过提供镁来促进间充质干细胞的成骨分化，并利用表没食子儿茶素-3-棓酸盐中和过量的活性氧（ROS），该涂层能增强间充质干细胞对有害应力的抵抗力，并为修复创造有利的微环境。E-Mg@MSC 可用于治疗电离辐射（IR）引起的造血损伤。有涂层的间充质干细胞能持续分泌造血生长因子，并精确地向辐射敏感组织归巢。体内研究显示，造血系统的恢复和多器官保护能力大大增强。机理研究表明，E-Mg@MSC 可减轻红外诱导的 ROS、细胞凋亡和铁变态反应，从而减少辐射损伤。该系统代表了利用功能材料进行细胞表面工程以促进间充质干细胞治疗的一种多功能且引人注目的策略。

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引用次数: 0

Engineering cell membrane-camouflaged COF-based nanosatellite for enhanced tumor-targeted photothermal chemoimmunotherapy 基于细胞膜伪装的 COF 纳米卫星工程，用于增强肿瘤靶向光热化疗免疫疗法。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122869

Dan Lin , Wenxin Lv , Min Qian , Guangwei Jiang , Xiaojun Lin , Darambazar Gantulga , Yi Wang

Dendritic cells (DCs) activation is crucial for regulating the antitumor immune response. However, the tumor's immunosuppressive environment significantly impedes antigen presentation and DCs maturation, thereby limiting the effectiveness of cancer immunotherapy. To address this challenge, we developed tumor cell membrane-coated covalent organic framework (COF) nanoparticles, loaded with mannose-modified gold nanoparticles and doxorubicin (Dox). This created a cell membrane-camouflaged COF-based nanosatellite designed to enhance tumor-targeted chemoimmunotherapy. The nanosatellite exhibits distinct photothermal properties and releases Dox in a pH-sensitive manner, targeting tumor cells to induce immunogenic cell death (ICD) and expose a wealth of antigens. Crucially, the COF structure is selectively degraded to release mannose-modified gold nanoparticles in the acidic environment. These nanoparticles capture antigens from the ICD and efficiently transport them to lymph nodes rich in DCs, facilitated by mannose receptor mediation. As a result, antigens are effectively presented to DCs, activating the immune response, significantly hindering tumor growth and lung metastasis in mice, and extending survival. This study pioneered innovative nano-preparations aimed at enhancing tumor immunotherapy.

树突状细胞（DCs）的激活对于调节抗肿瘤免疫反应至关重要。然而，肿瘤的免疫抑制环境极大地阻碍了抗原呈递和树突状细胞的成熟，从而限制了癌症免疫疗法的效果。为了应对这一挑战，我们开发了肿瘤细胞膜包被共价有机框架（COF）纳米粒子，其中装载了甘露糖修饰的金纳米粒子和多柔比星（Dox）。这样就产生了一种细胞膜掩蔽的基于 COF 的纳米卫星，旨在增强肿瘤靶向化疗免疫疗法。这种纳米卫星具有独特的光热特性，能以对 pH 值敏感的方式释放 Dox，靶向肿瘤细胞诱导免疫原性细胞死亡（ICD），并暴露大量抗原。最重要的是，COF 结构在酸性环境中会被选择性降解，释放出甘露糖修饰的金纳米粒子。这些纳米粒子能捕获 ICD 中的抗原，并在甘露糖受体介导下将其有效地输送到富含 DC 的淋巴结。因此，抗原能有效地呈现给直流电，激活免疫反应，显著阻碍小鼠的肿瘤生长和肺转移，延长生存期。这项研究开创了旨在增强肿瘤免疫疗法的创新纳米制剂。

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