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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 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 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 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
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 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
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 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。
{"title":"Shooting two hawks with one arrow: manganese-doped mesoporous carriers coordinate STING activation and enhanced mRNA translation for in situ cytokine delivery","authors":"Yakai Yan ,&nbsp;Liuyi Chen ,&nbsp;Yue Wu ,&nbsp;Xinrong Qu ,&nbsp;Xiang Ma ,&nbsp;Xing Sun ,&nbsp;Guangya Xiang ,&nbsp;Yao Lu","doi":"10.1016/j.mtbio.2026.102802","DOIUrl":"10.1016/j.mtbio.2026.102802","url":null,"abstract":"<div><div>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<sup>+</sup> 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.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102802"},"PeriodicalIF":10.2,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980882","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
Infection protection, immune regulation and epithelial regeneration trifunctional hydrogel for treatment of burn wounds 三功能水凝胶治疗烧伤创面的感染保护、免疫调节和上皮再生
IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-10 DOI: 10.1016/j.mtbio.2026.102788
Xingyue Chen , Jiachen Lu , Zhaojun Wu , Haopeng Zhang , Wei Zheng , Huanghe Zeng , Dongbiao Chang , Jie Weng , Jinsheng Li , Tailin Guo
Severe burn wounds are characterized by epithelial disruption and persistent inflammation, which impede re-epithelialization and heighten susceptibility to bacterial colonization and invasion, thereby posing serious clinical risks. To address these challenges, we developed an innovative smart hydrogel (Ag-IMP-U@Cur), in which uridine (U) is incorporated as a backbone-forming component via reversible boronate ester bonds with phenylboronic acid, thereby endowing the hydrogel with dual functions of acidic microenvironment responsiveness and promotion of re-epithelialization. The Ag-IMP complex serves as a structural scaffold that reinforces the network stability, while the combination of Ag-IMP and Cur-loaded ZIF-8 (Cur-ZIF-8) imparts controlled-release, antibacterial, and anti-inflammatory properties. In vitro and in vivo studies demonstrate that this hydrogel markedly suppresses infection and inflammation while accelerating wound closure. Collectively, this work introduces an innovative strategy that integrates a nucleoside unit, metal ions, and a phytochemical into a responsive multifunctional hydrogel, offering a promising therapeutic avenue for severe burn injuries.
严重烧伤创面的特点是上皮破坏和持续炎症,这阻碍了再上皮化,增加了细菌定植和入侵的易感性,从而带来了严重的临床风险。为了解决这些挑战,我们开发了一种创新的智能水凝胶(Ag-IMP-U@Cur),其中尿苷(U)通过与苯硼酸的可逆硼酸酯键结合作为骨架形成成分,从而赋予水凝胶双重功能,即酸性微环境响应性和促进再上皮化。Ag-IMP复合物作为结构支架,加强了网络的稳定性,而Ag-IMP和cu负载的ZIF-8 (cu -ZIF-8)的组合赋予了控释、抗菌和抗炎特性。体外和体内研究表明,这种水凝胶显著抑制感染和炎症,同时加速伤口愈合。总的来说,这项工作引入了一种创新的策略,将核苷单元、金属离子和植物化学物质整合到一种反应性多功能水凝胶中,为严重烧伤提供了一种有希望的治疗途径。
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引用次数: 0
Targeting IBD treatment: smart drug delivery systems for oral administration 靶向IBD治疗:口服给药的智能给药系统
IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-10 DOI: 10.1016/j.mtbio.2025.102758
Jiabin Xu , Peiyu Tang , Xiaoyi Sun , Yihan Song , Kaili Lin , Shan Jiang , Changyong Yuan
Inflammatory bowel disease is a global widespread condition that significantly reduces patients' quality of life. Conventional oral therapies suffer from poor site-specific targeting, systemic absorption, and limited drug stability, leading to reduced efficacy and adverse effects. Smart drug delivery systems have emerged as a promising strategy to overcome these challenges by leveraging stimuli-responsive mechanisms, including internal triggers (pH, reactive oxygen species, enzymes, receptors and microbiota) and external stimuli (magnetic fields, light, ultrasound and temperature). These advanced platforms enable precise, localized drug release, enhancing therapeutic efficacy, minimizing systemic toxicity, and improving patient compliance. Preclinical studies highlight their potential in prolonging remission and promoting mucosal healing. As research progresses, further optimization of formulation design, clinical validation, and addressing interpatient variability will be essential for translating these innovative drug delivery systems into effective clinical applications for IBD management. Herein, we summarize and discuss the rational design of smart oral drug delivery systems for IBD treatment, highlighting their mechanisms, therapeutic advantages, and current challenges. The potential clinical applications, along with existing limitations and future directions for optimizing these advanced delivery platforms, are also clarified.
炎症性肠病是一种全球普遍存在的疾病,会显著降低患者的生活质量。传统的口服治疗存在部位特异性靶向性差、全身吸收、药物稳定性有限等问题,导致疗效降低和不良反应。通过利用刺激响应机制,包括内部触发(pH值、活性氧、酶、受体和微生物群)和外部刺激(磁场、光、超声和温度),智能给药系统已经成为克服这些挑战的一种有希望的策略。这些先进的平台能够精确、局部地释放药物,提高治疗效果,最大限度地减少全身毒性,并提高患者的依从性。临床前研究强调了它们在延长缓解期和促进粘膜愈合方面的潜力。随着研究的进展,进一步优化配方设计、临床验证和解决患者之间的差异对于将这些创新的给药系统转化为IBD治疗的有效临床应用至关重要。在此,我们总结并讨论了用于IBD治疗的智能口服给药系统的合理设计,重点介绍了它们的机制、治疗优势和当前的挑战。阐明了潜在的临床应用,以及优化这些先进输送平台的现有限制和未来方向。
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引用次数: 0
Non-antibiotic lipid complex-in-thermogel strikes twice: multimodal photosensitive antibacterial meets immunomodulation-boosted healing for periodontitis treatment 非抗生素脂质复合物在热凝胶罢工两次:多模态光敏抗菌满足免疫调节促进牙周炎治疗愈合
IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-10 DOI: 10.1016/j.mtbio.2026.102781
Jing Li , Mengyuan Hou , Run Wang , Meng Li , Junying Chen , Minxuan Ge , Yachen Fei , Xianling Gao , Chengdong Zhang , Jin Zhong , Shuangying Gui , Mengjie Li , Jinghua Hao , Jian Guo
Periodontitis is a chronic oral disease characterized by gingival inflammation and periodontium injury due to repeated pathogenic bacteria infection and overactive inflammatory response. Multidrug resistance and the quick loss of antibiotics in the oral cavity create challenges for treatment. Therefore, a novel non-antibiotic-dependent pharmaceutical strategy is crucial for clinical treatment of periodontitis. In this study, we developed a lipid complex-in-thermogel delivery system (IQ-ML@Gel) co-loading the photosensitizer of indocyanine green and the immunomodulator of quercetin. IQ-ML@Gel could stably adhere in the periodontal pocket through liquid-solid transformation in situ. In vitro studies confirmed the efficient elimination of Porphyromonas gingivalis and Fusobacterium nucleatum by multimodal photothermal/photodynamic effects. Notably, IQ-ML displayed rapid macrophage uptake and an immunomodulatory effect through M1-M2 phenotypic polarization. In in vivo periodontitis treatment, IQ-ML@Gel effectively reverses the inflammatory microenvironment to promote periodontal tissue repair, including stimulating the regeneration of gingival collagen and alveolar bone. Overall, IQ-ML@Gel provides a promising non-antibiotic lipid complex-in-thermogel platform for periodontitis treatment.
牙周炎是一种慢性口腔疾病,以牙龈炎症和牙周组织损伤为特征,是由反复的病原菌感染和过度活跃的炎症反应引起的。多药耐药和口腔内抗生素的快速流失给治疗带来了挑战。因此,一种新的非抗生素依赖的药物策略对牙周炎的临床治疗至关重要。在这项研究中,我们开发了一种脂质复合物-热凝胶递送系统(IQ-ML@Gel),共负载吲哚菁绿光敏剂和槲皮素免疫调节剂。IQ-ML@Gel可通过原位液固转化在牙周袋内稳定粘附。体外研究证实了多模态光热/光动力效应对牙龈卟啉单胞菌和核梭杆菌的有效清除。值得注意的是,IQ-ML通过M1-M2表型极化表现出快速的巨噬细胞摄取和免疫调节作用。在体内牙周炎治疗中,IQ-ML@Gel有效逆转炎症微环境,促进牙周组织修复,包括刺激牙龈胶原和牙槽骨的再生。总的来说,IQ-ML@Gel为牙周炎治疗提供了一个很有前途的非抗生素热凝胶脂质复合物平台。
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引用次数: 0
Two-step formation of multilayered membrane pattern from living cells and probing its nanoscale physicochemical properties via nanopipette 活细胞两步形成多层膜图案并利用纳米吸管探测其纳米物理化学性质
IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-09 DOI: 10.1016/j.mtbio.2026.102787
Dong Wang , Alexis Borowiak , Linhao Sun
Cell membrane with varied physicochemical properties, e.g., morphology and surface charge, has played crucial roles in many life-related activities. Numerous artificial lipid bilayer membranes (LBM) have been used broadly as model systems to mimic natural cell membrane for studying these properties. However, precisely probing the nanoscale physicochemical properties of natural cell membranes with high resolution and sensitivity remains a key challenge. Here, we present a two-step method, namely, “dipping” and “writing”, using nanopipette to create multilayered lipid bilayer membrane (MLBM) derived from cell surface on substrates. During the dipping step, membrane components are adsorbed onto the inner wall of nanopipette, while the writing step enables the controlled deposition of MLBM onto the substrate. Physicochemical characterization reveals that MLBM undergoes dynamic formation, accompanied by frequent variations in membrane size and thickness. Surface charge mapping further demonstrates a heterogeneous charge distribution across the MLBMs, which is distinct from that of the substrate. This heterogeneity is primarily attributed to variations in membrane fluidity and thickness. Moreover, compared to artificial LBM, MLBMs produced via this two-step method allow the use of smaller apertures and higher ion current reduction setpoints, leading to significantly enhanced imaging resolution and detection sensitivity. This work offers a straightforward and efficient strategy for investigating nanoscale physicochemical properties of natural cell membranes. Additionally, the MLBMs serve as a versatile platform for future studies of membrane-related processes, such as biosensing and drug screening.
细胞膜具有不同的物理化学性质,如形态和表面电荷,在许多与生命有关的活动中起着至关重要的作用。许多人工脂质双层膜(LBM)被广泛用作模拟天然细胞膜的模型系统来研究这些特性。然而,高分辨率、高灵敏度地精确探测天然细胞膜的纳米级物理化学性质仍然是一个关键的挑战。在这里,我们提出了一种两步法,即“浸渍”和“写入”,利用纳米吸管在底物上从细胞表面制备多层脂质双层膜(MLBM)。在浸渍步骤中,膜组分被吸附到纳米吸管内壁上,而写入步骤使MLBM在衬底上的沉积得到控制。物理化学表征表明,MLBM经历动态形成,伴随着膜尺寸和厚度的频繁变化。表面电荷映射进一步证明了跨mlbm的非均匀电荷分布,这与衬底的不同。这种不均匀性主要归因于膜流动性和厚度的变化。此外,与人工LBM相比,通过这种两步法生产的mlbm允许使用更小的孔径和更高的离子电流还原设定值,从而显着提高成像分辨率和检测灵敏度。这项工作为研究天然细胞膜的纳米级物理化学性质提供了一种简单有效的策略。此外,mlbm为未来膜相关过程的研究提供了一个多功能平台,如生物传感和药物筛选。
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引用次数: 0
Sialic acid–guided spatiotemporal hydrogel therapy for liver cancer 唾液酸引导的时空水凝胶治疗肝癌
IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2026-01-08 DOI: 10.1016/j.mtbio.2026.102784
Weiqiang Hao , Hyeon Ji Kim , Jumi Kang , Bongkyun Kang , Seoyeon Park , Yuejin Kim , Eunjeong Kim , Kyueui Lee
Efficient delivery of plant-derived polyphenolic drugs to tumor sites in hepatocellular carcinoma (HCC) is challenging due to their rapid metabolism and the limited tumor-targeting capacity of current therapeutic strategies. To overcome these limitations, we developed a pH-responsive hydrogel-based drug delivery system (PA–CB) composed of a chitosan backbone functionalized with boronobenzoic acid (CB) and crosslinked with protocatechualdehyde (PA). Within this scaffold, protocatechuic acid (PCA) was incorporated as a model therapeutic agent to demonstrate the platform's ability to achieve controlled, pH-responsive release and to impart anticancer, anti-inflammatory, and antifibrotic effects through the action of the drug. The hydrogel, stabilized via boronate ester and Schiff-base linkages, maintained integrity under physiological conditions while enabling drug markedly enhanced anticancer efficacy in vitro compared to free PCA, including a near-complete reduction of HepG2 cell viability, migration, and colony formation, along with increased apoptosis. This enhanced antitumor efficacy was due to CB-mediated recognition of sialic acid residues on HCC cells, which facilitated tumor-selective accumulation and sustained drug release. Intraperitoneal administration of the hydrogel in an HCC mouse model significantly reduced tumor burden, hepatic inflammation, and fibrosis, while improving liver function markers. Histological assessments confirmed alleviation of liver injury, and quantitative polymerase chain reaction analyses revealed decreased expression of proinflammatory cytokines. Collectively, these results highlight this hydrogel platform as a robust strategy to stabilize phenolic drugs, achieve tumor-targeted delivery, and enable controlled release. These findings highlight its potential as an advanced therapeutic approach for HCC and a versatile framework applicable to other polyphenolic agents in oncology.
由于植物源性多酚类药物的快速代谢和目前治疗策略的肿瘤靶向能力有限,将其有效地递送到肝细胞癌(HCC)的肿瘤部位是一项挑战。为了克服这些限制,我们开发了一种ph响应的水凝胶药物递送系统(PA - CB),该系统由壳聚糖骨架与硼苯甲酸(CB)功能化并与原儿茶醛(PA)交联组成。在这个支架中,原儿茶酸(PCA)被纳入模型治疗剂,以证明该平台能够实现受控的、ph响应性释放,并通过药物的作用赋予抗癌、抗炎和抗纤维化作用。通过硼酸酯和希夫碱键稳定的水凝胶在生理条件下保持完整性,同时与游离PCA相比,使药物在体外显著增强抗癌功效,包括几乎完全降低HepG2细胞活力、迁移和集落形成,以及增加凋亡。这种增强的抗肿瘤功效是由于cb介导的唾液酸残基在HCC细胞上的识别,这促进了肿瘤选择性积累和持续的药物释放。在HCC小鼠模型中腹腔注射水凝胶可显著减少肿瘤负荷、肝脏炎症和纤维化,同时改善肝功能指标。组织学评估证实肝损伤减轻,定量聚合酶链反应分析显示促炎细胞因子表达降低。总的来说,这些结果突出了这种水凝胶平台作为稳定酚类药物、实现肿瘤靶向递送和控制释放的强大策略。这些发现突出了其作为HCC先进治疗方法的潜力,以及适用于肿瘤学中其他多酚类药物的多功能框架。
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Materials Today Bio
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