Materials Today Bio最新文献_第9页

Angiogenesis-facilitating and inflammation-modulating SIS-based patches coupled with functional peptides for abdominal wall repair 促进血管生成和炎症调节的基于sis的贴片与功能肽联合用于腹壁修复

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-13 DOI: 10.1016/j.mtbio.2026.102795

Zhenyu Zou , Yuchen Liu , Xueying Zhang , Jinxin Cao , Pengfei Wei , Yiqian Huang , Wei Jing , Bo Zhao , Minggang Wang

Abdominal wall defects caused by trauma, tumors, infections, abdominal surgery, and congenital factors can lead to functional impairments. The use of patches remains the most effective treatment approach. However, current repair materials still have limitations in regulating inflammation and promoting vascularization. Here, a small intestinal submucosa (SIS) extracellular patch was developed via conjugation with functional peptides PR1P and LL37 (i.e., SIS-PR1P-LL37), to achieve angiogenesis and inflammation modulation for abdominal wall repair. In vitro experiments confirmed its superior pro-angiogenic potential when human umbilical vein endothelial cells (HUVECs) were treated with the patch, both tube formation (total tube length: 4.51 ± 0.53 mm, junction count: 28.00 ± 4.97) and scratch wound repair (repair area 3.26-fold that of the SIS group) outperformed the native SIS group (average tube length: ∼1.3 mm). After 7 days of culture, the VEGF expression was higher than that in the SIS group, and the expression levels of key angiogenic genes (VEGF, VEGFR-2, etc.) were 5.45–7.82-fold higher than those in the control group. Additionally, this peptide-conjugated SIS patch could enhance cell proliferation and angiogenic differentiation, effectively reduce the levels of inflammatory cytokines, and enrich the TLR and VEGF signaling pathways. The rat abdominal wall defect model further confirmed its superior capacity for tissue regeneration and angiogenesis, indicating it provides important theoretical and experimental support for the development of novel bioactive patches and holding promise for optimizing clinical strategies for abdominal wall repair.

创伤、肿瘤、感染、腹部手术和先天性因素引起的腹壁缺损可导致功能障碍。使用贴片仍然是最有效的治疗方法。然而，目前的修复材料在调节炎症和促进血管化方面仍有局限性。在这里，通过与功能肽PR1P和LL37（即SIS-PR1P-LL37）结合，开发了小肠粘膜下层（SIS）细胞外贴片，以实现血管生成和炎症调节，以修复腹壁。体外实验证实了该贴片对人脐静脉内皮细胞（HUVECs）具有优越的促血管生成潜力，管的形成（总管长：4.51±0.53 mm，结数：28.00±4.97）和划伤修复（修复面积是SIS组的3.26倍）均优于天然SIS组（平均管长：~ 1.3 mm）。培养7 d后，VEGF表达高于SIS组，关键血管生成基因（VEGF、VEGFR-2等）表达水平较对照组高5.45 - 7.82倍。此外，该肽偶联的SIS贴片可促进细胞增殖和血管生成分化，有效降低炎症细胞因子水平，丰富TLR和VEGF信号通路。大鼠腹壁缺损模型进一步证实了其优越的组织再生和血管生成能力，为开发新型生物活性贴片提供了重要的理论和实验支持，并有望优化腹壁修复的临床策略。

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引用次数: 0

pH-responsive ZIF-8@quercetin nanoparticles induce pyroptosis for targeted gastric cancer therapy ph响应ZIF-8@quercetin纳米颗粒诱导胃癌靶向治疗焦亡

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-13 DOI: 10.1016/j.mtbio.2026.102806

Qian Xu , Xin Jin , Siyi Song , Hongyu Zhang , Huanxin Ding , Chuxuan Liu , Luyu Li , Shi Peng , Yugang Cheng , Mingwei Zhong , Linchuan Li , Jiankang Zhu , Shuohui Dong , Guangyong Zhang

Gastric cancer (GC) remains a major global health burden, with limited effective therapies and poor prognosis. Quercetin (Que), a natural flavonoid, exhibits anticancer activity but suffers from poor water solubility, limited oral bioavailability, and rapid metabolic clearance, which severely restrict its clinical translation. These pharmacokinetic limitations necessitate an efficient delivery system capable of stabilizing Que in circulation and enabling tumor-specific release. To address these limitations, a zeolitic imidazolate framework-8 (ZIF-8) was developed based on nanoparticles that encapsulate Que (ZIF-8@Que), enabling high loading efficiency and pH-responsive release. ZIF-8@Que was efficiently internalized by GC cells and localized within lysosomes, where the acidic environment accelerated drug release. This process coincided with marked reactive oxygen species (ROS) generation, leading to mitochondrial membrane depolarization, ATP depletion, and ultrastructural damage. Cellular analyses further revealed features consistent with pyroptotic cell death, including lactate dehydrogenase (LDH) release, increased staining for cleaved caspase-1 and cleaved gasdermin-D (GSDMD), and enhanced TUNEL-positive signals. Compared with free Que or empty ZIF-8, ZIF-8@Que demonstrated stronger inhibition of proliferation, migration, and invasion in vitro, while in vivo studies confirmed preferential tumor accumulation, robust tumor suppression, and minimal systemic toxicity. Collectively, these findings highlight ZIF-8@Que as a safe and effective nanoparticle that integrates drug delivery with ROS-mediated pyroptosis, offering a promising strategy to overcome the limitations of Que monotherapy and advance GC therapy.

胃癌（GC）仍然是全球主要的健康负担，有效治疗方法有限，预后不良。槲皮素（Quercetin, Que）是一种天然类黄酮，具有抗癌活性，但水溶性差，口服生物利用度有限，代谢清除快，严重限制了其临床转化。这些药代动力学限制需要一种有效的递送系统，能够稳定Que在循环中并使肿瘤特异性释放。为了解决这些限制，基于封装Que （ZIF-8@Que）的纳米颗粒开发了沸石咪唑盐框架-8 (ZIF-8)，实现了高负载效率和ph响应释放。ZIF-8@Que被GC细胞有效地内化并定位于溶酶体中，酸性环境加速了药物释放。这一过程与显著的活性氧（ROS）产生同时发生，导致线粒体膜去极化、ATP耗竭和超微结构损伤。细胞分析进一步揭示了与热腐细胞死亡相一致的特征，包括乳酸脱氢酶（LDH）释放，裂解caspase-1和裂解gasdermind （GSDMD）染色增加，tunel阳性信号增强。与游离的Que或空的ZIF-8相比，ZIF-8@Que在体外表现出更强的增殖、迁移和侵袭抑制作用，而体内研究证实了肿瘤的优先积累、强大的肿瘤抑制作用和最小的全身毒性。总的来说，这些发现强调ZIF-8@Que是一种安全有效的纳米颗粒，可以将药物传递与ros介导的焦死结合起来，为克服Que单药治疗的局限性和推进GC治疗提供了一种有希望的策略。

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引用次数: 0

Emerging roles of microfluidics in oral cancer research and clinical translation 微流体在口腔癌研究和临床转化中的新作用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-13 DOI: 10.1016/j.mtbio.2026.102801

Zi-Zhan Li , Li-Ya Wei , Lei-Ming Cao , Guang-Rui Wang , Han-Yue Luo , Kan Zhou , Xing-Zhong Zhao , Bing Liu , Ming-Xue Zheng , Chun Xu , Bo Cai , Lin-Lin Bu

Oral cancer remains a global health burden, with limited improvements in long-term survival despite advances in multimodal therapy. Advances in early diagnosis and treatment strategies for oral cancer patients will significantly improve survival outcomes. Microfluidic technology, with its capacity for precise fluid manipulation, high-throughput analysis, and experimental miniaturization, has emerged as a powerful tool to accelerate innovations in cancer research and has become a pivotal pathway in oral cancer investigation and clinical translation. This review systematically examines the expanding roles of microfluidics in oral cancer research, with a particular focus on microfluidics-based liquid biopsy for early detection and prognosis, and microfluidics-enabled therapeutic strategies for treatment development and optimization. By bridging basic research with clinical application, microfluidics holds the potential to revolutionize early diagnosis, precision therapeutics, and functional outcome-oriented management in oral cancer, ultimately improving patient survival and quality of life.

口腔癌仍然是全球健康负担，尽管多模式治疗取得进展，但长期生存率的改善有限。口腔癌患者早期诊断和治疗策略的进步将显著改善生存结果。微流体技术以其精确的流体操作、高通量分析和实验小型化的能力，已经成为加速癌症研究创新的有力工具，并已成为口腔癌研究和临床转化的关键途径。这篇综述系统地探讨了微流体技术在口腔癌研究中的扩展作用，特别关注了基于微流体技术的早期检测和预后的液体活检，以及微流体技术在治疗开发和优化方面的治疗策略。通过将基础研究与临床应用相结合，微流体技术有望彻底改变口腔癌的早期诊断、精确治疗和以功能结果为导向的管理，最终提高患者的生存率和生活质量。

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引用次数: 0

NIR-II biomimetic nanoplatform optogenetic CD274 editing of HNSCC immunogenicity for enhanced photoimmunotherapy NIR-II仿生纳米平台光遗传CD274编辑HNSCC免疫原性增强光免疫治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-13 DOI: 10.1016/j.mtbio.2026.102803

Yang Chen , Longcai Liu , Xiaojuan Hu , Yilin Huang , Shijie Yao , Lichen Ji , Hai Zou , Xiaozhou Mou , Yu Cai

Although immunotherapy has achieved impressive breakthroughs in head and neck squamous cell carcinoma (HNSCC), it still encounters significant challenges such as the intrinsic low immunogenicity microenvironment and limited T cell infiltration. In this work, we aimed to edit the CD274 gene of HNSCC cells by optogenetics with second near-infrared (NIR-II) light, thereby reducing the CD274 expression and improving the efficacy of photo-immunogenic therapy. Specifically, a biomimetic nanoplatform (ARPC) was established by using an α-LDLR (low density lipoprotein receptor antibody) engineered red blood cell membrane (RBCm) to deliver NIR-II photothermal polymers and CRISPR/Cas9 plasmids. After intravenous injection into HNSCC-bearing mice, ARPC can induce heat stress upon NIR-II laser irradiation at tumor sites, causing the upregulation of Hsp70 to trigger CRISPR/Cas9 for CD274 editing. Moreover, the mild photothermal therapeutic effect of ARPC simultaneously induced immunogenic cell death in tumor cells for enhancing CD8⁺ T cell infiltration and proliferation, and thereby leading to photoimmunotherapy. This study provides an NIR-II optogenetic CRISPR/Cas9 CD274 for editing reprogrammed photo-immunogenic therapy strategy, showing great clinical potential for overcoming the low immunogenicity of HNSCC.

尽管免疫疗法在头颈部鳞状细胞癌（HNSCC）治疗中取得了令人瞩目的突破，但仍面临着固有的低免疫原性微环境和有限的T细胞浸润等重大挑战。本研究旨在利用二次近红外（NIR-II）光遗传学技术对HNSCC细胞的CD274基因进行编辑，从而降低CD274的表达，提高光免疫原治疗的效果。具体而言，利用α-低密度脂蛋白受体抗体（低密度脂蛋白受体抗体）工程红血膜（RBCm）构建了一个仿生纳米平台（ARPC），以传递NIR-II光热聚合物和CRISPR/Cas9质粒。经静脉注射至携带hnscc的小鼠后，ARPC可在NIR-II激光照射肿瘤部位诱导热应激，导致Hsp70上调，触发CRISPR/Cas9对CD274进行编辑。此外，ARPC的轻度光热治疗作用同时诱导肿瘤细胞的免疫原性细胞死亡，增强CD8+ T细胞的浸润和增殖，从而导致光免疫治疗。本研究提供了一种NIR-II光遗传CRISPR/Cas9 CD274编辑重编程光免疫原性治疗策略，在克服HNSCC低免疫原性方面显示出巨大的临床潜力。

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引用次数: 0

Stiff matrix promotes lung cancer cell migration through down-regulating the Piezo1 channel expression to facilitate Ca2+-dependent filopodia formation 硬基质通过下调Piezo1通道表达促进Ca2+依赖性丝状足形成，从而促进肺癌细胞迁移

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102786

Xiaoling Jia , Lin Zhao , Juncheng Bai , Lu Wen , Qianyu Meng , Haikun Wang , Junqi Men , Hui Shao , Yingying Guo , Xinlan Chen , Xing Chen , Lin-Hua Jiang , Yubo Fan , Huawei Liu

Matrix stiffening profoundly influences cancer cell functions and cancer progression, and the mechanosensitive Piezo1 channel is implicated in these processes. Different from what is observed in most solid tumors, the Piezo1 channel in lung cancer is down-regulated and negatively regulates cancer cell migration, but the underlying mechanism is still unclear. Herein, we investigated the role of Piezo1 channel in matrix stiffness regulation of lung cancer cell migration and the mechanisms in A549 cells growing on polyacrylamide (PA) hydrogels with different stiffness. Compared with soft substrate, stiff substrate promoted cell migration, down-regulated Piezo1 expression, favored filopodia formation, as well as restraining the rise in intracellular calcium concentration ([Ca²⁺]_i). Additionally, blockade or knockdown of Piezo1 channel promoted, whereas its activation suppressed, cell migration and filopodia formation. Furthermore, reducing the [Ca²⁺]_i promoted cell migration and filopodia formation. Finally, stiff substrate induced cofilin phosphorylation, which was enhanced by inhibiting the Piezo1 channel or reducing the [Ca²⁺]_i and, conversely, suppressed by activating the Piezo1 channel. Collectively, our study has revealed that stiff matrix down-regulates the Piezo1 channel expression and thereby restrains the rise in the [Ca²⁺]_i to facilitate cofilin phosphorylation and filopodia formation, leading to an increase in lung cancer cell migration. These findings broaden our understanding of the molecular mechanism by which the Piezo1 channel functions in lung cancer differently from in other cancers.

基质硬化深刻影响癌细胞功能和癌症进展，而机械敏感的Piezo1通道参与了这些过程。与在大多数实体肿瘤中观察到的不同，肺癌中的Piezo1通道下调并负向调节癌细胞迁移，但其潜在机制尚不清楚。本文研究了Piezo1通道在基质刚度调节肺癌细胞迁移中的作用，以及在不同刚度的聚丙烯酰胺（PA）水凝胶上生长的A549细胞的机制。与软底物相比，硬底物促进细胞迁移，下调Piezo1表达，有利于丝状足的形成，抑制细胞内钙浓度（[Ca2+]i）的升高。此外，阻断或敲低Piezo1通道促进细胞迁移和丝状足形成，而其激活抑制细胞迁移和丝状足形成。此外，降低[Ca2+]i可促进细胞迁移和丝状足的形成。最后，刚性底物诱导cofilin磷酸化，通过抑制Piezo1通道或减少[Ca2+]i来增强，相反，通过激活Piezo1通道来抑制。总的来说，我们的研究表明，硬基质下调了Piezo1通道的表达，从而抑制了[Ca2+]i的升高，从而促进了cofilin的磷酸化和丝状足的形成，导致肺癌细胞迁移的增加。这些发现扩大了我们对Piezo1通道在肺癌中不同于其他癌症中的功能的分子机制的理解。

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引用次数: 0

Alendronic acid modified PLGA drug delivery system loaded with 17β-Estradiol and vitamin D3 has anti-osteoporotic effect 阿仑膦酸修饰PLGA载17β-雌二醇和维生素D3给药系统具有抗骨质疏松作用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102789

Yonghui Wang , Sidi Zhang , Xinrun Ma , Donghao Hu , Junran Liu , Lu Wei , Xue Lei , Yan Hu , Fuyou Li , Yanhong Gao

Postmenopausal osteoporosis caused by estrogen deficiency often requires hormone replacement therapy (HRT), but its systemic side effects limit clinical application. Here, we developed a bone-targeted Poly (lactic-co-glycolic acid) (PLGA) nanocarrier modified with Alendronic acid (ADA) to co-deliver 17β-Estradiol (E2) and Vitamin D3 (VitD3), aiming to enhance efficacy and safety. The ADA-functionalized nanoparticles (E2+VD@PLGA_IR780ADA) showed high drug loading (7.2 wt% for E2 and 2.3 wt% for VitD3), sustained release (>90 % over 48 h). In ovariectomized (OVX) mice, targeted delivery significantly improved bone mineral density, restored trabecular structure, and reduced serum bone resorption markers, while markedly alleviating E2-induced endometrial thickening. In vivo imaging confirmed selective bone accumulation. Mechanistically, co-administration of VitD3 and E2 elicits enhanced pro-osteogenic effects by virtue of VitD3-mediated Vitamin D Receptor (VDR) upregulation and amplified E2-induced estrogen receptor (ER) expression, which collectively drive robust activation of the PI3K/AKT/mTOR signaling cascade.This bone-specific nanoplatform offers a promising and safer strategy for osteoporosis therapy beyond conventional HRT.

雌激素缺乏引起的绝经后骨质疏松症通常需要激素替代治疗（HRT），但其全身副作用限制了临床应用。本研究以阿仑膦酸（ADA）修饰的聚乳酸-羟基乙酸（PLGA）为骨靶向纳米载体，共同递送17β-雌二醇（E2）和维生素D3 (VitD3)，旨在提高其疗效和安全性。ada功能化纳米颗粒（E2+VD@PLGAIR780ADA）显示出高载药量（E2为7.2 wt%， VitD3为2.3 wt%），缓释（48小时内缓释90%）。在卵巢切除（OVX）小鼠中，靶向递送显著改善骨密度，恢复小梁结构，降低血清骨吸收标志物，同时显著减轻e2诱导的子宫内膜增厚。体内成像证实选择性骨积聚。从机制上讲，通过VitD3介导的维生素D受体（VDR）上调和E2诱导的雌激素受体（ER）表达扩增，VitD3和E2联合使用可增强促成骨作用，从而共同驱动PI3K/AKT/mTOR信号级联的强大激活。这种骨特异性纳米平台为骨质疏松症治疗提供了一种比传统激素替代疗法更有前途和更安全的策略。

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引用次数: 0

TZM Mo alloy behaves superb as biodegradable metal for bone-fracture healing intramedullary nail implant TZM钼合金作为生物可降解金属，在骨折愈合髓内钉植入物中表现优异

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102794

Junyu Qian , Yukun Zhou , Zhenhai Xie , Jinjing Liu , Ping Li , Wenjie Tao , Yuanhao Wang , Fei Gao , Hui Zeng , Deli Wang , Haotian Qin , Yingqi Chen , Guojiang Wan

Bone fracture repair, particularly assisted by load-bearing implants, faces tough clinical challenges, necessitating novel biomaterials that are mechanically strong, biocompatible and biodegradable to achieve effective healing. Metallic molybdenum (Mo) has shown promise in this regard, whereas little has been done with considering its alloys that are more advantageous on many aspects over its pure counterpart. Herein, we demonstrate that the TZM Mo alloy (namely Titanium-Zirconium-Molybdenum, also Mo-Ti-Zr) performed superb efficacy in the repair of rat femoral fractures with its intramedullary nails (IMNs) prototype product even as compared with pure Mo. The TZM alloy had superior mechanical strength and more uniform degradation than Mo, meeting the requirements for next-generation biodegradable IMNs. Moreover, the in vitro assays verified the TZM promoted adhesion, migration and proliferation of endothelial cells and bone marrow mesenchymal stem cells and elicited no toxicity. Molecular expression results revealed the TZM may enhance angiogenesis by activating Wnt/β-catenin signaling and facilitated bone formation by up-regulating osteogenic genes via PI3K–Akt, MAPK–ERK, and cAMP–PKA pathways. More important, TZM-based IMNs achieved nearly complete fracture healing at 12 weeks in a rat femoral fracture model. Thus, the TZM Mo alloy holds super potential for clinical translation.

骨折修复，特别是在承重植入物的辅助下，面临着严峻的临床挑战，需要机械强度高、生物相容性好、可生物降解的新型生物材料来实现有效的愈合。金属钼（Mo）在这方面显示出了希望，而很少有人考虑它的合金在许多方面比纯钼更有优势。本研究证明，与纯Mo相比，TZM Mo合金（即钛锆钼，Mo- ti - zr）的髓内钉（IMNs）原型产品在大鼠股骨骨折的修复中表现出极好的效果。TZM合金具有比Mo更好的机械强度和更均匀的降解，满足下一代可生物降解IMNs的要求。此外，体外实验证实了TZM对内皮细胞和骨髓间充质干细胞的粘附、迁移和增殖有促进作用，且无毒性。分子表达结果显示，TZM可能通过激活Wnt/β-catenin信号通路促进血管生成，并通过PI3K-Akt、MAPK-ERK和cAMP-PKA通路上调成骨基因促进骨形成。更重要的是，在大鼠股骨骨折模型中，基于tzm的IMNs在12周时实现了几乎完全的骨折愈合。因此，TZM钼合金具有超强的临床转化潜力。

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引用次数: 0

Expanding the toolbox of bioorthogonal activation of photosensitizers for precise photodynamic therapy through transition metal-mediated deallylation 扩展光敏剂的生物正交激活工具箱，通过过渡金属介导的去氧化进行精确的光动力治疗

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102797

Feijie Xu, Qianqian Wu, Lin He, Lin Yang, Pui-Chi Lo

The development of bioorthogonal activation of photosensitizers represents a promising avenue for precise photodynamic therapy (PDT) against cancer. It requires effective decaging strategies that can be applied in vivo, but such highly efficient and biocompatible methodologies remain scarce. We report herein the first use of ruthenium-mediated bioorthogonal deallylation for on-demand activation of boron dipyrromethene (BDP)-based photosensitizers. In this study, we first prepared a series of BDP-based photosensitizers connected to an allyl group with or without a self-immolative spacer via an ester caging unit [Pro-BDP-n (n = 1–4)] and studied their activation upon treatment with several ruthenium complexes [RuLn (n = 1–3)]. Pro-BDP-3, having a methoxy substituent at the self-immolative linker, was found to exhibit the highest release efficiency and fastest decaging kinetics. Using RuL3 as activator, which was modified with a biotin moiety, Pro-BDP-3 could be selectively activated in the endoplasmic reticulum (ER) of biotin receptor-overexpressed cancer cells. The induced ER stress disturbed the intracellular calcium homeostasis and ER-mitochondria crosstalk, resulting in mitochondria dysfunction and eventually cell death via apoptosis. The high treatment efficacy of this approach was also demonstrated in vivo. This work expands the toolbox of bioorthogonal activation of photosensitizers using transition metal-promoted deallylation as an efficient decaging strategy.

光敏剂生物正交活化的发展为精确光动力治疗癌症提供了一条有前景的途径。它需要有效的降解策略，可以在体内应用，但这种高效和生物相容性的方法仍然稀缺。我们在此报告了首次使用钌介导的生物正交脱烷基来按需激活硼二吡咯甲烷（BDP）基光敏剂。在本研究中，我们首先通过酯笼单元[Pro-BDP-n (n = 1-4)]制备了一系列基于bdp的光敏剂，这些光敏剂与烯丙基连接，有或没有自溶间隔物[Pro-BDP-n] (n = 1-4)，并研究了几种钌配合物[RuLn (n = 1-3)]对它们的活化作用。亲- bdp -3具有最高的释放效率和最快的衰减动力学，在自燃烧连接体上具有甲氧基取代基。使用生物素修饰的RuL3作为激活剂，Pro-BDP-3可以在生物素受体过表达的癌细胞内质网（ER）中选择性激活。内质网应激干扰细胞内钙稳态和内质网线粒体串扰，导致线粒体功能障碍，最终细胞凋亡死亡。体内实验也证明了该方法的高治疗效果。这项工作扩展了光敏剂的生物正交活化工具箱，使用过渡金属促进脱烷基作为有效的衰减策略。

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引用次数: 0

Shooting two hawks with one arrow: manganese-doped mesoporous carriers coordinate STING activation and enhanced mRNA translation for in situ cytokine delivery 一箭双雕：锰掺杂介孔载体协调STING激活和增强mRNA翻译，以实现细胞因子的原位传递

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102802

Yakai Yan , Liuyi Chen , Yue Wu , Xinrong Qu , Xiang Ma , Xing Sun , Guangya Xiang , Yao Lu

Cytokine mRNAs, such as IL-12, hold significant promise for anti-tumor therapy. However, their effective localized delivery and the prevention of off-target translation remain challenging. To address these challenges, we synthesized manganese-doped organic mesoporous carriers for mRNA delivery (PMSMns). The Mn doping in PMSMns not only boosted mRNA expression but also enhanced the immune response. Mechanistically, we verified that PMSMns enhance the translation process by relieving glyceraldehyde 3-phosphate dehydrogenase-mediated translational repression and upregulating the level of phosphorylated ribosomal protein S6. Meanwhile, the immune response was enhanced by activating the stimulator of interferon genes (STING) pathway. Furthermore, effective local delivery of mRNA only in tumors without off-target expression in other organs was also achieved. The PMSMns-IL-12/15-mRNA group exhibited the highest levels of IFN-γ, the greatest infiltration of CD8⁺ T cells, and the most robust recruitment of NK cells, achieving a potent synergistic antitumor effect. Overall, PMSMns provide a dual benefit: boosting mRNA translation and activating the STING pathway, making them ideally suited for cytokine mRNA-based tumor therapy.

细胞因子mrna，如IL-12，在抗肿瘤治疗中具有重要的前景。然而，它们的有效本地化传递和防止脱靶翻译仍然是一个挑战。为了解决这些挑战，我们合成了锰掺杂的有机介孔mRNA递送载体（PMSMns）。在PMSMns中掺杂Mn不仅可以提高mRNA的表达，还可以增强免疫应答。在机制上，我们证实PMSMns通过缓解甘油醛3-磷酸脱氢酶介导的翻译抑制和上调磷酸化核糖体蛋白S6的水平来增强翻译过程。同时，激活干扰素基因刺激因子（STING）通路可增强免疫应答。此外，还实现了mRNA仅在肿瘤中有效的局部递送，而在其他器官中没有脱靶表达。PMSMns-IL-12/15-mRNA组表现出最高水平的IFN-γ，最大的CD8+ T细胞浸润和最强大的NK细胞募集，实现了有效的协同抗肿瘤作用。总的来说，PMSMns提供了双重好处：促进mRNA翻译和激活STING途径，使它们非常适合细胞因子mRNA为基础的肿瘤治疗。

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引用次数: 0

Ultrasound-responsive hydrogel with ROS scavenging and NO controllable release capabilities for accelerated healing of diabetic wounds 具有ROS清除和NO可控释放能力的超声响应水凝胶加速糖尿病伤口愈合

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-01-12 DOI: 10.1016/j.mtbio.2026.102796

Jialei Luo , Xinyi Yan , Kang Fu , Yuxuan Qiu , Yana Xu , Zhaojie Wang , Xuexiao Li , Ting Lin , Ying Wang , Yunting Zhang , Yawei Yu , Shibo Wang , Jianqing Gao , Gaoyi Yang

Diabetic wounds represent a common and challenging complication of diabetes mellitus, characterized by a complex pathological microenvironment that includes excessive reactive oxygen species (ROS), chronic inflammation, hypoxia, and impaired nitric oxide (NO) synthesis. These factors collectively contribute to delayed wound healing, increased infection risk, and potential progression to chronic non-healing ulcers. Herein, we constructed a multifunctional injectable hydrogel (Prussian blue nanozyme and S-nitrosothiol-loaded hydrogel, PBE&SNO@HG) co-loaded with multi-enzyme-mimicking Prussian blue nanozymes (PBE) and an ultrasound-responsive nitric oxide (NO) donor (SNO). This composite hydrogel exhibited favorable injectability and tissue adhesiveness. The incorporated PBE nanozymes simultaneously mimicked superoxide dismutase (SOD) and catalase (CAT), enabling the scavenging of superoxide anions (⋅O₂⁻) and hydrogen peroxide (H₂O₂), thereby reducing oxidative stress levels at the wound site. Additionally, the ultrasound (US)-responsive release of NO promoted angiogenesis and alleviates inflammatory responses in the wound area. Animal experiments demonstrated that this hydrogel system significantly enhances collagen deposition, accelerates re-epithelialization, promotes hair follicle regeneration, and accelerates wound healing. This study demonstrated the synergistic effect of combining antioxidant strategies with gas therapy in diabetic wound treatment, while also indicating that US-responsive hydrogel materials can achieve on-demand release of therapeutic molecules via external field stimulation, thereby providing a novel strategy for chronic wound management.

糖尿病伤口是糖尿病常见且具有挑战性的并发症，其特征是复杂的病理微环境，包括活性氧（ROS）过量、慢性炎症、缺氧和一氧化氮（NO）合成受损。这些因素共同导致伤口愈合延迟，感染风险增加，并可能发展为慢性不愈合溃疡。在此，我们构建了一种多功能可注射水凝胶（普鲁士蓝纳米酶和负载s -亚硝基硫醇的水凝胶，PBE&SNO@HG），共负载多种酶模拟普鲁士蓝纳米酶（PBE）和超声响应的一氧化氮（NO）供体（SNO）。该复合水凝胶具有良好的注射性和组织粘附性。加入的PBE纳米酶同时模拟超氧化物歧化酶（SOD）和过氧化氢酶（CAT），能够清除超氧化物阴离子（⋅O2−）和过氧化氢（H2O2），从而降低伤口部位的氧化应激水平。此外，超声（US）反应性释放NO促进血管生成，减轻创面炎症反应。动物实验证明，该水凝胶体系能显著促进胶原沉积，加速再上皮化，促进毛囊再生，加速伤口愈合。本研究证明了将抗氧化策略与气体治疗相结合在糖尿病创面治疗中的协同作用，同时也表明us反应水凝胶材料可以通过外场刺激实现治疗分子的按需释放，从而为慢性创面治疗提供了一种新的策略。

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引用次数: 0