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Biomimetic pore-throat engineered ultrahigh molecular weight polyethylene with sustained tea polyphenol release for infection-resistant joint implant material 仿生孔喉工程超高分子量聚乙烯茶多酚持续释放抗感染关节植入材料。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-17 DOI: 10.1016/j.colsurfb.2026.115458
Kang Li , Yi-Zi Wang , Shao-Peng Zhao , Peiqi Yu , Zhi Qiao , Mengfan Jing , Yaming Wang , Yue Ren , Yu Han , Chuntai Liu
To address the limitations of systemic antibiotics in treating prosthetic joint infections (PJI), ultrahigh molecular weight polyethylene (UHMWPE)-based polyphenol delivery systems have been developed as an antibiotic-free strategy. However, challenges exist in achieving sustained antimicrobial efficacy and enhancing overall performance. To achieve threshold-insensitive sustained release, a biomimetic pore-throat structure inspired by geologic capillary transport mechanisms was engineered within UHMWPE. This structure was constructed through strategic co-incorporation of polyethylene oxide (PEO) and a sub-permeation-threshold tea polyphenol (epigallocatechin gallate, EGCG as representative). PEO-encapsulated EGCG clusters formed expanded pore-throat networks with enhanced distribution uniformity, facilitated by hydrogen bonding between PEO’s ether groups and EGCG’s phenolic hydroxyls. This microstructure enabled swelling-regulated drug release obeying Korsmeyer-Peppas kinetics. The PEO concentration directly modulated sustained EGCG release through capillary action and swelling-erosion. The resulting composites achieved > 80 % antibacterial efficacy against major pathogens while PEO simultaneously formed boundary-hydrated lubrication layers that reduced the friction coefficient to 0.065. Combined with favorable biocompatibility and effective suppression of bacterial-induced inflammation, this biomimetic strategy establishes a material-level, proof-of-concept approach with potential for future development toward infection-resistant orthopedic devices.
为了解决全身抗生素治疗假体关节感染(PJI)的局限性,基于超高分子量聚乙烯(UHMWPE)的多酚递送系统已被开发为一种无抗生素的策略。然而,在实现持续的抗菌功效和提高整体性能方面存在挑战。为了实现阈值不敏感的持续释放,在UHMWPE中设计了一种受地质毛细管输送机制启发的仿生孔喉结构。该结构是通过聚乙烯氧化物(PEO)和亚渗透阈值茶多酚(表没食子儿茶素没食子酸酯,EGCG为代表)的战略性共结合而构建的。PEO封装的EGCG簇形成了扩展的孔喉网络,分布均匀性增强,PEO的醚基团和EGCG的酚羟基之间的氢键促进了这一点。这种微观结构使肿胀调节的药物释放服从Korsmeyer-Peppas动力学。PEO浓度通过毛细管作用和溶胀侵蚀直接调节EGCG的持续释放。复合材料对主要病原菌的抗菌效果达到了> 80 %,同时PEO形成了边界水合润滑层,使摩擦系数降低到0.065。结合良好的生物相容性和有效抑制细菌诱导的炎症,这种仿生策略建立了一种材料水平的概念验证方法,具有未来开发抗感染骨科设备的潜力。
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引用次数: 0
Hyaluronic acid-based strategies for prostate cancer therapy 基于透明质酸的前列腺癌治疗策略
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-14 DOI: 10.1016/j.colsurfb.2026.115448
Xueling Lan , Qunhua Zhou , Haitong Wang , Zhongyi Mu , Liyang Pan , Liqun Yang , Qiang Du
Hyaluronic acid (HA) has emerged as a pivotal biomaterial in prostate cancer management, bridging the gap between physical tissue spacing and targeted molecular therapy. While HA-based hydrogels are clinically established, and nanomedicines are rapidly evolving, a comprehensive integration of these distinct domains remains lacking. This review critically synthesizes the dual roles of HA in prostate cancer radiotherapy and drug delivery. We first delineate the biological basis of HA, emphasizing its interactions with CD44/RHAMM receptors and the implications for material design. Clinically, we systematically evaluate the efficacy of HA hydrogel spacers across diverse radiotherapy modalities, including SBRT, brachytherapy, and hypofractionated regimens, highlighting their quantitative impact on prostate-rectum separation and the substantial reduction of gastrointestinal toxicity. Beyond physical spacing, we analyze the translational status of HA-based nanocarriers, discussing their potential to overcome drug resistance through receptor-mediated active targeting. Crucially, we address significant limitations in current strategies, such as the structural heterogeneity arising from imprecise chemical modifications and the lack of standardized in vivo stability evaluation systems. Finally, we propose a roadmap for future research, advocating for subtype-specific material design, the development of intelligent stimuli-responsive derivatives, and synergy with emerging immunotherapies to realize precision medicine in prostate cancer.
透明质酸(HA)已成为前列腺癌治疗中的关键生物材料,弥合了物理组织间距和靶向分子治疗之间的差距。虽然基于ha的水凝胶在临床上已经建立,纳米药物也在迅速发展,但这些不同领域的全面整合仍然缺乏。本文综述了透明质酸在前列腺癌放疗和给药中的双重作用。我们首先描述了透明质酸的生物学基础,强调了它与CD44/RHAMM受体的相互作用以及对材料设计的影响。在临床上,我们系统地评估了透明质酸水凝胶间隔剂在不同放疗方式下的疗效,包括SBRT、近距离放疗和低分割放疗方案,强调了它们对前列腺-直肠分离的定量影响和对胃肠道毒性的实质性降低。除了物理间隔,我们分析了ha基纳米载体的翻译状态,讨论了它们通过受体介导的主动靶向克服耐药性的潜力。至关重要的是,我们解决了当前策略的重大局限性,例如由不精确的化学修饰引起的结构异质性和缺乏标准化的体内稳定性评估系统。最后,我们提出了未来研究的路线图,倡导亚型特异性材料设计,智能刺激反应衍生物的开发,并与新兴的免疫疗法协同实现前列腺癌的精准医疗。
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引用次数: 0
Temperature-responsive hydrogel delivery of antimicrobial peptide engineered watermelon-derived extracellular vesicles enables sequential infection control and wound healing 温度敏感的水凝胶递送抗菌肽工程西瓜来源的细胞外囊泡,使顺序感染控制和伤口愈合
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-12 DOI: 10.1016/j.colsurfb.2026.115438
Ziyang Bai , Yifan Zhao , Yajuan Gong , Meijun Du , Wenjun Zhang , Ke Zhang , Yongchao Zhi , Yanan Nie , Xia Li , Xiuping Wu , Bing Li
Infected wounds present major clinical challenges due to excessive bacterial colonization, sustained inflammation, and impaired tissue repair. To address these barriers, we developed a temperature-responsive hydrogel delivery system incorporating watermelon-derived extracellular vesicles (wEV), antimicrobial peptide-engineered for the topical treatment of infected wounds. wEVs contained terpenoids, flavonoids, alkaloids, and proteins with intrinsic anti-inflammatory and pro-regenerative activity. To enhance stability and antibacterial potency, antimicrobial peptides (AMP) were conjugated to wEVs via mussel derivatives, producing wEV-AMP. These were embedded in a temperature-responsive Pluronic F127/chitosan hydrogel that gels at 37 °C for wound coverage and controlled release. In vitro, PF127/CS+wEV-AMP inhibited > 95 % of Staphylococcus aureus and Escherichia coli, suppressed biofilms, reduced inflammatory cytokines, and enhanced fibroblast migration. In infected rat wounds, healing rate reached ∼60 % by day 5 and nearly complete closure by day 14, with greater collagen deposition and M2 macrophage polarization. This multifunctional hydrogel integrates antimicrobial, immunomodulatory, and regenerative effects, offering strong potential for infectious wound treatment.
由于细菌定植过多、持续炎症和组织修复受损,感染伤口目前是主要的临床挑战。为了解决这些障碍,我们开发了一种温度敏感的水凝胶递送系统,该系统包含西瓜来源的细胞外囊泡(wEV),抗菌肽工程用于局部治疗感染伤口。wev含有萜类、黄酮类、生物碱和蛋白质,具有内在的抗炎和促再生活性。为了提高抗菌肽(AMP)的稳定性和抗菌效力,我们将抗菌肽(AMP)通过贻贝衍生物偶联到wev上,生成wEV-AMP。它们被包埋在温度敏感的Pluronic F127/壳聚糖水凝胶中,该水凝胶在37 °C下凝胶化,用于伤口覆盖和控制释放。在体外,PF127/CS+wEV-AMP抑制金黄色葡萄球菌和大肠杆菌>; 95 %,抑制生物膜,减少炎症细胞因子,增强成纤维细胞迁移。在感染的大鼠伤口中,到第5天,愈合率达到~ 60% %,到第14天几乎完全闭合,胶原沉积和M2巨噬细胞极化增加。这种多功能水凝胶集抗菌、免疫调节和再生作用于一体,为感染性伤口治疗提供了强大的潜力。
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引用次数: 0
Lysosome-targeted ROS-responsive graphene oxide-based drug delivery system to overcome tumor DOX resistance 溶酶体靶向ros响应的氧化石墨烯给药系统克服肿瘤DOX耐药
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-10 DOI: 10.1016/j.colsurfb.2026.115434
Fengzhu Yang , Jintao Deng , Xinyu Yu , Wenhao Fu , Wenlong Sun , Zhengbao Xu , Xinhua Song , Chao Wang , Qingqing Du , Meng Wang
The lysosomes of drug-resistant tumor cells transport doxorubicin (DOX) and its nanocarriers into lysosomes through a sequestration mechanism, making it difficult for DOX to reach the therapeutic concentration. In this study, a nanodrug delivery system (Dp/DGPP) capable of overcoming tumor lysosomal resistance was developed. The system consists of three parts: graphene oxide (GO)-Se-Se-DOX, polyethyleneimine-pluronic F127 (PEI-PF127) for improved biocompatibility, and Dp44mT for amplifying reactive oxygen species (ROS) and disrupting lysosomes. After entering MCF-7/ADR tumor cells, loading Dp44mT can reduce the permeability of lysosomal membranes by increasing the level of ROS. DOX subsequently escapes from lysosomes and breaks the diselenide bond to complete its release. The experiment proved that Dp/DGPP exhibited a significant ROS-dependent response to the release of DOX. Compared with the other groups, it had greater cytotoxicity, and the IC50 value of DOX against MCF-7/ADR cells was as low as 6.71 μM. Compared with the DOX group, the Dp/DGPP group exhibited greater DOX accumulation in MCF-7/ADR cells, with 1.5-fold greater fluorescence at 4 h. Meanwhile, Dp/DGPP can cause lysosomal dysfunction by reducing lysosomal membrane permeability. Western blot results revealed that the expression of Pgp protein decreased in the Dp/DGPP group, whereas the expression of autophagy related LC3-II and P62 protein increased, which confirmed that autophagic flux was blocked. This reduces potential drug resistance and promotes cell death. In addition, the Dp/DGPP group achieved a 70 % inhibition rate in MCF-7/ADR tumors in vivo. This nanodrug delivery system provides a potential strategy to overcome tumor DOX resistance via lysosomes.
耐药肿瘤细胞溶酶体通过固存机制将多柔比星(DOX)及其纳米载体转运到溶酶体中,使DOX难以达到治疗浓度。在这项研究中,开发了一种能够克服肿瘤溶酶体耐药的纳米药物递送系统(Dp/DGPP)。该系统由三部分组成:氧化石墨烯(GO)-Se-Se-DOX,用于改善生物相容性的聚乙烯亚胺-pluronic F127 (PEI-PF127),以及用于扩增活性氧(ROS)和破坏溶酶体的Dp44mT。在进入MCF-7/ADR肿瘤细胞后,负载Dp44mT可通过增加ROS水平降低溶酶体膜的通透性。DOX随后从溶酶体中逃逸并打破二硒化物键以完成释放。实验证明,Dp/DGPP对DOX的释放表现出明显的ros依赖性反应。与其他组相比,DOX对MCF-7/ADR细胞的IC50值低至6.71 μM。与DOX组相比,Dp/DGPP组在MCF-7/ADR细胞中表现出更大的DOX积累,在4 h时荧光增加1.5倍。同时,Dp/DGPP可通过降低溶酶体膜通透性引起溶酶体功能障碍。Western blot结果显示,Dp/DGPP组Pgp蛋白表达降低,而自噬相关LC3-II和P62蛋白表达升高,证实自噬通量被阻断。这减少了潜在的耐药性并促进细胞死亡。此外,Dp/DGPP组在体内对MCF-7/ADR肿瘤的抑制率达到70 %。这种纳米药物递送系统提供了一种通过溶酶体克服肿瘤DOX耐药的潜在策略。
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引用次数: 0
Design, characterization, and in vitro evaluation of Eudragit-coated aminated mesoporous silica nanoparticles loaded with pterostilbene for colon delivery 设计、表征和体外评价载紫菀芪的涂膜胺化介孔二氧化硅纳米颗粒结肠递送
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-15 DOI: 10.1016/j.colsurfb.2026.115452
Nikhil Raut , Manasa N. , Swornahuti Panda, Victor Hmingthangsanga, Subramanian Natesan
Ulcerative colitis (UC), a chronic inflammatory colon disease, often requires long-term care. Pterostilbene (PTB), a naturally occurring substance with strong anti-inflammatory and antioxidant properties, has shown therapeutic potential; however, its poor aqueous solubility and instability at stomach pH limit its clinical application. A colon-targeted drug delivery system loaded with PTB and coated with Eudragit S100 (EU) was developed using mesoporous silica nanoparticles (MSN). The MSN were surface-aminated using 3-aminopropyl triethoxysilane (APTES) to obtain aminated mesoporous silica nanoparticles (AMSN), which provided pH-responsive release and enhanced drug binding. FT-IR spectroscopy confirmed the encapsulation of the drug and amine functionalization through characteristic spectral shifts. X-ray diffraction (XRD) showed decreased crystallinity of PTB, suggesting effective molecular dispersion within the MSN matrix. Differential scanning calorimetry (DSC) was used to confirm the amorphous form of the encapsulated medication. Morphological study using SEM and TEM revealed consistently spherical, porous nanoparticles. Thermogravimetric analysis (TGA) demonstrated the formulation's thermal stability, and Brunauer-Emmett-Teller (BET) analysis showed high surface area and pore volume, both of which are advantageous for efficient drug loading. In vitro release investigations confirmed a pH-dependent, extended release of the drug under intestinal conditions. Additionally, pro-inflammatory cytokines (TNF-α and IL-6) were significantly reduced in the ELISA assays of LPS-stimulated HT-29 cells, demonstrating the formulation's anti-inflammatory efficacy. The development of colon-specific delivery of pterostilbene, the Eudragit-coated PTB-loaded AMSN (Eu-PTB-AMSN), effectively addresses the primary shortcomings of conventional PTB formulations, including low solubility, stomach instability, and systemic adverse effects, while offering a practical therapeutic approach for the treatment of UC.
溃疡性结肠炎(UC)是一种慢性炎症性结肠疾病,通常需要长期护理。紫檀芪(PTB)是一种天然存在的具有强抗炎和抗氧化特性的物质,已显示出治疗潜力;但其水溶性差,胃pH值不稳定,限制了其临床应用。利用介孔二氧化硅纳米颗粒(MSN)制备了一种载PTB并包被Eudragit S100 (EU)的结肠靶向给药系统。利用3-氨基丙基三乙氧基硅烷(APTES)对微球表面进行胺化,得到胺化介孔二氧化硅纳米颗粒(AMSN),该纳米颗粒具有ph响应释放和增强药物结合的特性。傅里叶变换红外光谱通过特征光谱位移证实了药物的包封和胺的功能化。x射线衍射(XRD)表明PTB的结晶度降低,表明在MSN基体中存在有效的分子分散。用差示扫描量热法(DSC)确定了包封药物的无定形。利用扫描电镜和透射电镜对纳米颗粒进行了形态学研究,结果表明纳米颗粒呈球形、多孔。热重分析(TGA)表明该制剂具有良好的热稳定性;比表面积和孔容分析(BET)表明该制剂具有较高的比表面积和孔容,有利于高效载药。体外释放调查证实了ph依赖性,延长了药物在肠道条件下的释放。此外,在lps刺激的HT-29细胞的ELISA检测中,促炎细胞因子(TNF-α和IL-6)显著降低,证明该配方具有抗炎功效。紫芪二苯乙烯的结肠特异性递送,eudragte涂层PTB负载AMSN (Eu-PTB-AMSN)的开发,有效解决了传统PTB配方的主要缺点,包括低溶解度,胃不稳定和全身不良反应,同时为UC的治疗提供了一种实用的治疗方法。
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引用次数: 0
Surface-enhanced Raman scattering (SERS) in antibiotic resistance detection: Advances, challenges, and future perspectives 表面增强拉曼散射(SERS)在抗生素耐药性检测中的应用:进展、挑战和未来展望
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-08 DOI: 10.1016/j.colsurfb.2026.115423
Biqing Chen , Jiayin Gao , Haizhu Sun , Yan Liu , Yinghan Zhao , Xiaohong Qiu , Yang Li
Antimicrobial resistance (AMR) has emerged as one of the most critical global public health crises, causing an estimated 700,000 deaths annually according to the World Health Organization. Achieving early, rapid, and accurate detection and identification of drug-resistant bacteria is essential to addressing this challenge. Surface-enhanced Raman scattering (SERS), a highly sensitive, label-free, and non-invasive optical detection technology, has demonstrated great potential in bacterial identification and antimicrobial resistance analysis. In recent years, the integration of SERS with artificial intelligence (AI) technologies particularly machine learning (ML) and deep learning (DL) methods has enabled unprecedented accuracy and efficiency in resistance detection. This review systematically summarizes recent advances in SERS–AI combined strategies for AMR detection, analyzes the strengths and limitations of various approaches, and explores their potential applications in clinical and surveillance settings. Finally, the importance of continuous technological innovation and interdisciplinary collaboration in this field is emphasized to promote the translational application of SERS–AI strategies in the global fight against AMR.
抗菌素耐药性(AMR)已成为最严重的全球公共卫生危机之一,据世界卫生组织估计,每年造成70万人死亡。实现耐药细菌的早期、快速和准确检测和鉴定对于应对这一挑战至关重要。表面增强拉曼散射(SERS)是一种高灵敏度、无标记、无创的光学检测技术,在细菌鉴定和抗菌药物耐药性分析中显示出巨大的潜力。近年来,SERS与人工智能(AI)技术,特别是机器学习(ML)和深度学习(DL)方法的集成,使电阻检测的准确性和效率达到了前所未有的水平。本文系统总结了SERS-AI联合检测AMR策略的最新进展,分析了各种方法的优势和局限性,并探讨了它们在临床和监测环境中的潜在应用。最后,强调了该领域持续技术创新和跨学科合作的重要性,以促进SERS-AI战略在全球抗AMR斗争中的转化应用。
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引用次数: 0
Osteoinductive sandwich-structured HA/PEEK implant for rapid critical-size skull repair 骨诱导夹层结构HA/PEEK植入物用于快速修复临界尺寸颅骨
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-06 DOI: 10.1016/j.colsurfb.2026.115428
Mei-li Qi , Kunshan Yuan , Enhui Song , Xiangyi Feng , Tianheng Lu , Lin Zhao , Haihong Guo , Haijun Zhang
Critical-size bone defects afflict millions annually, driving a cascade of inflammation and incomplete tissue regeneration. Polyetheretherketone (PEEK) remains the material of choice for load-bearing implants because its modulus mirrors that of cortical bone; yet its notorious bioinertness curtails both anti-inflammatory signaling and osseointegration, stalling the healing process. To break this stalemate, we designed a sandwich-structured, osteoinductive hydroxyapatite (HA)/PEEK implant tailored for skull repair. A porous PEEK core was engineered via the salting out technique and its surface was homogeneously functionalized with HA through simple physical blending, preserving the implant’s open porosity while imparting potent osteoinductive activity. In a rabbit critical calvarial defect (10 mm diameter), new bone advanced from the periphery to the center, achieving full osseous continuity within only 4 months and markedly surpassing unmodified PEEK. The robust bone-implant integration demonstrated by this sandwich HA/PEEK construct not only converts a bioinert polymer into an osteoinductive implant but also may expand treatment options for growing children, offering a clinically translatable solution for skull repair after trauma, hemorrhage, tumor resection, or congenital dysplasia.
严重的骨缺损每年折磨数百万人,引发一连串的炎症和不完全的组织再生。聚醚醚酮(PEEK)仍然是承重植入物的首选材料,因为它的模量与皮质骨相似;然而,其臭名昭著的生物惰性限制了抗炎信号和骨整合,延缓了愈合过程。为了打破这一僵局,我们设计了一种三明治结构的骨诱导羟基磷灰石(HA)/PEEK植入物,专门用于颅骨修复。通过盐析技术设计多孔PEEK芯,其表面通过简单的物理混合与透明质酸均匀功能化,保留了植入物的开放孔隙度,同时赋予了有效的骨诱导活性。在兔严重颅骨缺损(10 mm直径)中,新骨从周围向中心推进,仅在4个月内实现了完全的骨连续性,明显优于未修饰的PEEK。这种夹层HA/PEEK结构所展示的强大的骨植入整合不仅将生物惰性聚合物转化为骨诱导植入物,而且还可以为成长中的儿童提供更多的治疗选择,为创伤、出血、肿瘤切除或先天性发育不良后的颅骨修复提供临床可翻译的解决方案。
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引用次数: 0
Combining lactate oxidase and metformin in cancer cell membrane-biomimetic liposomes for synergistic ferroptosis induction and hypoxia-alleviated cancer therapy 结合乳酸氧化酶和二甲双胍在肿瘤细胞膜-仿生脂质体中协同诱导铁下垂和减轻缺氧的癌症治疗
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-07 DOI: 10.1016/j.colsurfb.2026.115420
Cheng-Lei Li , Feng-Ming Li , Ke-Ke Feng , Yong-Shan Hu , Yi-Fan Tu , Shi-Cheng Tian , Zhen-Hua Liu , Jing-Wei Shao
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxide accumulation, offers a promising strategy to circumvent tumor drug resistance. However, solid tumors exhibit intrinsic resistance to ferroptosis due to elevated antioxidant systems and hypoxic microenvironments, limiting H₂O₂-mediated lipid peroxidation. Herein, we developed a tumor-homing liposomal platform (ML-MLip) for co-delivery of lactate oxidase (LOX) and metformin (MET) to leverage the tumor microenvironment for enhanced ferroptosis induction. LOX catalyzes intratumoral abundant lactate (due to the Warburg effect) to generate H₂O₂, while MET alleviates tumor hypoxia by inhibiting mitochondrial complex I, ensuring sufficient oxygen for LOX activity. Concurrently, MET suppresses SLC7A11-mediated GSH synthesis and disabling GPX4-mediated lipid peroxide detoxification. Soybean phosphatidylcholine (SPC) within ML-MLip provides polyunsaturated lipids as substrates for peroxidation, overcoming endogenous lipid shortages. In vitro and in vivo studies demonstrated that ML-MLip preferentially accumulated at tumor sites, triggering iron-dependent lipid peroxidation (LPO) and ferroptosis. Additionally, lactate depletion and ferroptosis reversed the tumor immunosuppressive microenvironment, promoting the release of tumor antigens and damage-associated molecular patterns (DAMPs) to augment systemic immune responses. This strategy converts tumor-specific metabolites (lactate) and ions (iron) into therapeutic effectors, offering a microenvironment-responsive approach for synergistic ferroptosis-immunotherapy against malignant tumors.
铁凋亡是一种由脂质过氧化积累驱动的铁依赖性细胞死亡形式,为规避肿瘤耐药提供了一种有希望的策略。然而,实体瘤由于抗氧化系统和缺氧微环境的升高,限制了h2o2介导的脂质过氧化作用,表现出对铁上吊的内在抗性。在此,我们开发了一种肿瘤归家脂质体平台(ML-MLip),用于乳酸氧化酶(LOX)和二甲双胍(MET)的共同递送,以利用肿瘤微环境增强铁上吊诱导。LOX催化肿瘤内丰富的乳酸(由于Warburg效应)生成H₂O₂,而MET通过抑制线粒体复合体I缓解肿瘤缺氧,保证LOX活性所需的足够氧气。同时,MET抑制slc7a11介导的GSH合成,并使gpx4介导的脂质过氧化解毒失效。大豆磷脂酰胆碱(SPC)在ML-MLip中提供多不饱和脂质作为过氧化的底物,克服内源性脂质短缺。体外和体内研究表明,ML-MLip优先积聚在肿瘤部位,引发铁依赖性脂质过氧化(LPO)和铁下垂。此外,乳酸消耗和铁下垂逆转了肿瘤免疫抑制微环境,促进肿瘤抗原和损伤相关分子模式(DAMPs)的释放,以增强全身免疫反应。该策略将肿瘤特异性代谢物(乳酸盐)和离子(铁)转化为治疗效应器,为恶性肿瘤的协同铁中毒免疫治疗提供了微环境响应方法。
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引用次数: 0
Incorporating Mn²⁺ ions in bioactive sol-gel coatings: Impact on cell adhesion, inflammation and bone regeneration 在生物活性溶胶-凝胶涂层中加入Mn 2 +:对细胞粘附、炎症和骨再生的影响。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-10 DOI: 10.1016/j.colsurfb.2026.115436
C. Arias-Mainer , F. Romero-Gavilán , L. Abenia-Artigas , I. García-Arnáez , O. Amorrotu , M. Azkargorta , F. Elortza , M. Gurruchaga , I. Goñi , J. Suay
Manganese (Mn), an essential trace element involved in bone metabolism, plays a crucial role in key biological functions, including the regulation of cell adhesion, modulation of immune responses, and promotion of osteogenesis. In this study, sol-gel coatings with increasing concentrations of MnCl₂ (0.5, 1 and 1.5 % wt) were synthesised and applied onto titanium (Ti) surfaces. The materials were characterised physicochemically, and in vitro responses were assessed using human osteoblasts (HOb) and THP-1-derived macrophages. Protein adsorption from human serum was analysed by nLC-MS/MS. The incorporation of MnCl₂ did not disrupt the sol-gel silica network and enabled a sustained release of Mn²⁺ ions, and all coatings showed good biocompatibility with no cytotoxicity. Immune response analysis revealed that 0.5Mn promoted anti-inflammatory markers (IL-10, TGF-β), while 1Mn and 1.5Mn induced strong proinflammatory profiles, reflected in increased TNF-α and IL-1β. Proteomics identified preferential adsorption of immune-related proteins such as complement components, ficolins, acute-phase proteins and apolipoproteins to 1Mn and 1.5Mn. Conversely, 0.5Mn enhanced the adsorption of proteins linked to anti-inflammatory effects and oxidative stress regulation. Mn-doped surfaces also enhanced gene expression related to cell adhesion (CTNNB1, ITG1B, PTK2) and osteogenic markers (RUNX2, BMP2, BGLAP), particularly on 1.5Mn, correlating with increased calcium deposition and adsorption of mineralisation-related proteins (FETUA, ECM1, IGF2). All Mn sol-gel coatings promoted the coagulation cascade through increased adsorption of FA9, FA12 and ZPI. These results demonstrate the capacity of Mn-doped sol-gel coatings to modulate immune and osteogenic responses, underscoring the relevance of optimising Mn concentration to improve bone–implant integration.
锰(Mn)是骨代谢中必需的微量元素,在调节细胞粘附、调节免疫反应和促进成骨等关键生物学功能中起着至关重要的作用。在这项研究中,合成了增加MnCl₂浓度(0.5,1和1.5 % wt)的溶胶-凝胶涂层,并将其应用于钛(Ti)表面。对材料进行物理化学表征,并使用人成骨细胞(HOb)和thp -1来源的巨噬细胞评估体外反应。采用nLC-MS/MS分析了人血清中蛋白质的吸附。MnCl 2的掺入不会破坏溶胶-凝胶二氧化硅网络,使Mn 2 +离子能够持续释放,并且所有涂层都表现出良好的生物相容性,没有细胞毒性。免疫应答分析显示,0.5Mn可促进抗炎标志物(IL-10、TGF-β),而1Mn和1.5Mn可诱导强促炎,表现为TNF-α和IL-1β升高。蛋白质组学鉴定出免疫相关蛋白如补体成分、炎性蛋白、急性期蛋白和载脂蛋白对1Mn和1.5Mn的优先吸附。相反,0.5Mn增强了与抗炎作用和氧化应激调节有关的蛋白质的吸附。mn掺杂表面也增强了与细胞粘附相关的基因表达(CTNNB1, ITG1B, PTK2)和成骨标志物(RUNX2, BMP2, BGLAP),特别是在1.5Mn上,与钙沉积增加和矿化相关蛋白(FETUA, ECM1, IGF2)的吸附相关。所有Mn溶胶-凝胶涂层通过增加FA9、FA12和ZPI的吸附来促进混凝级联。这些结果证明了Mn掺杂溶胶-凝胶涂层调节免疫和成骨反应的能力,强调了优化Mn浓度与改善骨植入体整合的相关性。
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引用次数: 0
Luteolin-loaded nanocomposites target microglia for sepsis-associated encephalopathy therapy via intranasal delivery 木犀草素负载的纳米复合材料通过鼻内递送靶向小胶质细胞用于败血症相关脑病治疗。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2026-05-01 Epub Date: 2026-01-14 DOI: 10.1016/j.colsurfb.2026.115433
Weihong Guo , Tao Liu , Xiaojia Peng , Jiafa Zhang , Zhefeng Chen , Chongshuang Xia , Canhong Yang , Shuting Xie , Tianming Lü
Sepsis-associated encephalopathy (SAE) is a neurological dysfunction resulting from sepsis, with neuroinflammation identified as a key pathogenic mechanism. Luteolin (LUT) is a dietary polyphenol that possesses considerable therapeutic potential. However, its application is hindered by poor aqueous solubility, low absorption, and rapid metabolism. To address these challenges, we developed luteolin-loaded lactoferrin-chondroitin sulfate nanoparticles (LUT-LF-CS NPs) to enhance the bioavailability of LUT and evaluate its efficacy in alleviating neuroinflammation in SAE. The optimized LUT-LF-CS NPs exhibited a uniform particle size of 45.9 nm and an encapsulation efficiency of 71.73 %. These nanocomposites demonstrated excellent cytocompatibility and enhanced the intrinsic antioxidant and anti-inflammatory activities of LUT. Furthermore, they facilitated cellular uptake in microglia through CD44 receptor-mediated endocytosis, enabling effective drug delivery to the cerebral cortex after intranasal administration. Mechanistically, LUT-LF-CS NPs promoted the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype while inhibiting the TLR4/MyD88/NF-κB signaling pathway. In conclusion, LUT-LF-CS NPs significantly enhance the neuroprotective effects of LUT, positioning them as a promising therapeutic strategy for SAE.
脓毒症相关脑病(SAE)是一种由脓毒症引起的神经功能障碍,神经炎症被认为是主要的致病机制。木犀草素(LUT)是一种具有相当治疗潜力的膳食多酚。但其水溶性差、吸收率低、代谢快等缺点阻碍了其应用。为了解决这些挑战,我们开发了装载木犀草素的乳铁蛋白-硫酸软骨素纳米颗粒(LUT- lf - cs NPs),以提高LUT的生物利用度,并评估其缓解SAE神经炎症的功效。优化后的LUT-LF-CS NPs粒径均匀,为45.9 nm,包封效率为71.73 %。这些纳米复合材料表现出良好的细胞相容性,增强了LUT固有的抗氧化和抗炎活性。此外,它们通过CD44受体介导的内吞作用促进小胶质细胞的细胞摄取,从而在鼻内给药后有效地将药物递送到大脑皮层。在机制上,LUT-LF-CS NPs促进小胶质细胞从促炎M1表型向抗炎M2表型极化,同时抑制TLR4/MyD88/NF-κB信号通路。总之,LUT- lf - cs NPs显著增强了LUT的神经保护作用,使其成为一种有前景的SAE治疗策略。
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Colloids and Surfaces B: Biointerfaces
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