Colloids and Surfaces B: Biointerfaces最新文献_第8页

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

Colloids and Surfaces B: Biointerfaces

Pub 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

Innovative applications and future challenges of shape memory scaffolds for functional reconstruction in diseases of the musculoskeletal system 形状记忆支架在肌肉骨骼系统疾病功能重建中的创新应用和未来挑战。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-09 DOI: 10.1016/j.colsurfb.2026.115426

Zhengguang Pu , Wang Gong , Haoming Wu , Hao Zhou , YiXuan Lan , Yingying Chen , Xiuxing Liu , Zhineng Lu , Xiaoyu Du , Xinlei Yang , Shuhao Yang , Wanyue Feng , Chao Peng , Hai Lan , Xulin Hu

Musculoskeletal disorders (MSDs), such as osteoporosis, cartilage degeneration, and tendon injuries, are common worldwide and have a significant impact on patients' quality of life. These conditions are frequently associated with aging, trauma, or chronic diseases. They are typically characterized by slow and limited self-repair, particularly in tissues like cartilage and tendons, which exhibit low regenerative potential. Traditional treatment methods, such as implantable scaffolds, often face challenges related to incomplete tissue integration and inadequate adaptation to dynamic biomechanical conditions. Shape memory scaffolds (SMSs) have emerged as promising candidates for repairing musculoskeletal tissues, due to their unique ability to respond to external stimuli, such as temperature, light, and pH. These materials can adapt to irregular tissue defects and dynamically adjust to biomechanical requirements during the healing process, thereby potentially supporting tissue regeneration. This review discusses the advantages of SMSs in musculoskeletal system reconstruction, emphasizing their mechanical responsiveness, adaptability, and bioactive potential. Furthermore, recent advancements in SMS-based scaffolds and the role of 4D printing in enhancing their functionality are systematically reviewed. Finally, we propose future research directions aimed at enabling more effective and personalized treatments for MSDs.

肌肉骨骼疾病（MSDs），如骨质疏松症、软骨变性和肌腱损伤，在世界范围内很常见，并对患者的生活质量产生重大影响。这些情况通常与衰老、创伤或慢性疾病有关。它们的典型特征是缓慢和有限的自我修复，特别是在软骨和肌腱等组织中，它们表现出较低的再生潜力。传统的治疗方法，如植入式支架，往往面临着组织整合不完整和对动态生物力学条件适应不足的挑战。形状记忆支架（SMSs）由于其对外部刺激（如温度、光和ph）的独特响应能力而成为修复肌肉骨骼组织的有希望的候选者。这些材料可以适应不规则的组织缺陷，并在愈合过程中动态调整生物力学要求，从而潜在地支持组织再生。本文讨论了SMSs在肌肉骨骼系统重建中的优势，强调了它们的机械反应性、适应性和生物活性潜力。此外，系统地回顾了基于sms的支架的最新进展以及4D打印在增强其功能方面的作用。最后，我们提出了未来的研究方向，旨在实现更有效和个性化的治疗MSDs。

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引用次数: 0

Conformal polypyrrole biointerfaces on porous PHA monoliths via oxidative chemical vapor deposition 通过氧化化学气相沉积在多孔PHA单体上的保形聚吡咯生物界面。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-09 DOI: 10.1016/j.colsurfb.2026.115417

Adriana Kovalcik , Nicole Cernekova , Fika Fauzi , Ranjita K. Bose , Zdenko Spitalsky , Zuzana Kadlecova , Lucy Vojtova , Zdenka Víchová , Petr Humpolíček , Patrycja Bober

Chronic wounds require dressings that manage exudate, conform to soft tissue, provide mechanical support, and deliver intrinsic bioactivity. Here, we report conductive, hydrogel-like porous polyhydroxyalkanoate (PHA) monoliths dressings coated with polypyrrole (PPy) using oxidative chemical vapor deposition (oCVD). Porous PHA substrates were prepared from polyhydroxybutyrate (PHB) and a P4HB-containing copolymer by thermally induced phase separation and were uniformly functionalized throughout their three-dimensional architecture by this solvent-free process. The resulting PHA/PPy porous monoliths combine high water uptake with electrical conductivity and biological activity. They exhibit a swelling ratio of ∼250 %, maintaining a moist environment while preserving viscoelastic integrity. Sheet resistance ranges from 26 to 86 kΩ/sq, enabling platforms for electrical sensing in tissue repair. The composites do not induce cytotoxicity and exhibit intrinsic radical-scavenging capacity and antibacterial activity against both Gram-positive and Gram-negative bacteria. These properties are achieved without chemical derivatization of the PHA matrix. The hydrophobic PHA core provides mechanical robustness, while the conformal PPy layer imparts conductivity and bioactivity. Overall, this oCVD route provides a scalable, solvent-free strategy to engineer multifunctional, hydrogel-like porous monolith dressings that integrate moisture management, mechanical resilience, electrical conduction, and inherent antioxidant and antimicrobial activity. These features position the developed materials as promising bioactive and bioelectronic wound dressings and soft tissue interfaces.

慢性伤口需要处理渗出物的敷料，符合软组织，提供机械支持，并提供内在的生物活性。在这里，我们报道了利用氧化化学气相沉积（oCVD）技术涂覆聚吡咯（PPy）的导电、水凝胶状多孔聚羟基烷酸酯（PHA）单块敷料。以聚羟基丁酸酯（PHB）和含p4hb的共聚物为原料，通过热诱导相分离制备了多孔PHA底物，并通过无溶剂工艺在其三维结构中实现了均匀的功能化。由此产生的PHA/PPy多孔单体结合了高吸水性、导电性和生物活性。它们的膨胀率为~ 250 %，在保持粘弹性完整性的同时保持潮湿的环境。薄片电阻范围从26到86 kΩ/sq，使组织修复中的电传感平台成为可能。复合材料不诱导细胞毒性，对革兰氏阳性和革兰氏阴性细菌均具有内在的自由基清除能力和抗菌活性。这些性质的实现没有化学衍生的PHA基质。疏水性PHA核心提供机械坚固性，而保形PPy层提供导电性和生物活性。总的来说，这种oCVD路线提供了一种可扩展的、无溶剂的策略，用于设计多功能、水凝胶状多孔整体敷料，该敷料集水分管理、机械弹性、导电性和固有的抗氧化和抗菌活性于一体。这些特点使所开发的材料成为有前景的生物活性和生物电子伤口敷料和软组织界面。

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引用次数: 0

Characterizations and controlled drug release behavior of acyclovir-loaded starch-based microneedles patches for transdermal herpes simplex virus therapy 经皮单纯疱疹病毒治疗无环韦淀粉基微针贴剂的特性和控释行为。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-09 DOI: 10.1016/j.colsurfb.2026.115430

Kyeongjung Kim , Se-woon Choe , Jae-Young Je , Min-Jin Hwang , Yoonhang Lee , Do-Hyung Kim , Kwangcheol Casey Jeong , Soon-Do Yoon

Transdermal drug delivery systems (TDDS) using microneedles (MNs) patches have shown promise for improved therapeutic outcomes. In this study, acyclovir (ACV)-loaded MNs patches for herpes simplex virus (HSV) therapy were prepared using mungbean starch (MBS), polyvinyl alcohol (PVA), and plasticizers (arginine and mannitol), and their physicochemical properties, ACV release behavior, antimicrobial activity, and biodegradation, cell viability, and antiviral efficacy were investigated. The MNs exhibited compression forces of 1.30 – 4.80 N/needle and a pyramidal square shape with a length of 620–640 μm, ensuring efficient skin penetration. The ACV release (%) from the ACV-loaded MNs patches during an artificial skin test was found to be 2.50 – 4.32 times higher than that from ACV-loaded biomaterial as the film-type formulation. Additionally, over 98.0 % of ACV was released from the prepared MNs patches within 80 min. The ACV release mechanism was analyzed using zero-order, first-order, Higuchi, Fickian diffusion, and Korsmeyer-Peppas models, which revealed a Fickian diffusion mechanism. Visualization of intradermal drug release were conducted using ACV- and riboflavin-loaded MNs patches on agar blocks and pig ears/agar block models. Biodegradability, cell viability, and antiviral studies further demonstrated the potential of MNs patches as a TDDS. These results suggest that the prepared MNs patches are promising candidates for transdermal HSV therapy.

使用微针（MNs）贴片的经皮给药系统（TDDS）已显示出改善治疗结果的希望。本研究以绿豆淀粉（MBS）、聚乙烯醇（PVA）和增塑剂（精氨酸和甘露醇）为原料制备了用于单纯疱疹病毒（HSV）治疗的无环鸟苷（ACV）负载MNs贴片，并对其物理化学性质、ACV释放行为、抗菌活性、生物降解、细胞活力和抗病毒效果进行了研究。纳米粒子的压缩力为1.30 ~ 4.80 N/针，呈金字塔形，长度为620 ~ 640 μm，可有效穿透皮肤。在人工皮肤试验中发现，载ACV的MNs贴片的ACV释放量（%）比载ACV的生物材料作为薄膜型制剂高2.50 ~ 4.32倍。此外，制备的MNs贴片在80 min内释放了超过98.0%的ACV。采用零阶、一阶、Higuchi、Fickian扩散和Korsmeyer-Peppas模型分析了ACV的释放机制，揭示了Fickian扩散机制。在琼脂块和猪耳/琼脂块模型上使用装载ACV和核黄素的MNs贴片进行皮内药物释放可视化。生物降解性、细胞活力和抗病毒研究进一步证明了MNs贴片作为TDDS的潜力。这些结果表明，制备的MNs贴片是经皮治疗HSV的有希望的候选者。

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引用次数: 0

Chitosan-based bimodal photosensitive system: Synergistic realization of visible light viscosity imaging and near-infrared type I photodynamic therapy 壳聚糖双峰光敏系统：可见光黏度成像和近红外I型光动力治疗的协同实现

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-09 DOI: 10.1016/j.colsurfb.2026.115432

Bo Zhao , Xinjian Cheng , Junyu Chen , Chenghua Zhang , Jun Liu

The integration of bioimaging and photodynamic therapy (PDT) joins real-time visualization with spatially controlled therapeutic activation, thus presenting a promising theranostic platform for precision oncology. However, the clinical translation of conventional photosensitizers suffers from limited tissue penetration and potential photodamage. To overcome these shortcomings, we proposed a NIR responsive system in this work. A naphthalimide-based small molecule (NQL) was synthesized, followed by oligo-chitosan conjugation through Schiff base formation, yielding the water-soluble probe CS-NQL. CS-NQL exhibits a twisted intramolecular charge transfer (TICT) state. It also has the capability to target lysosomes. This enables CS-NQL to respond to environmental viscosity, with target lysosomes. The CS-NQL was then electrostatically self-assembled with DNA to form nanoparticles (CS-NQL@DNA NPs). These nanoparticles (NPs) can generate reactive oxygen species (ROS) under 660 nm laser irradiation, exhibiting photosensitivity. Further detection using commercial reagents revealed this photosensitivity stems via Type I process. Critically, this oxygen-independent mechanism retained the ability to generate ROS under hypoxia, overcoming the limitations of the tumor microenvironment. Under 660 nm laser irradiation (0.4 W/cm²) for 20 min, NPs generate ROS, leading to apoptosis in over 90 % of HeLa cells and demonstrating antitumor effects. In vivo experiments, it is demonstrated that the NPs exhibited PDT after 30 min of 660 nm laser irradiation, achieving significant tumor suppression.

生物成像和光动力治疗（PDT）的整合将实时可视化与空间控制的治疗激活结合起来，从而为精确肿瘤学提供了一个有前途的治疗平台。然而，传统光敏剂的临床转化受到组织渗透有限和潜在光损伤的影响。为了克服这些缺点，我们在这项工作中提出了一个近红外响应系统。合成了萘酰亚胺基小分子（NQL），通过席夫碱形成低聚壳聚糖偶联，得到了水溶性探针CS-NQL。CS-NQL表现出扭曲的分子内电荷转移（TICT）态。它还具有靶向溶酶体的能力。这使得CS-NQL能够通过靶溶酶体对环境粘度做出反应。然后将CS-NQL与DNA静电自组装形成纳米颗粒（CS-NQL@DNA NPs）。这些纳米粒子（NPs）在660 nm激光照射下可产生活性氧（ROS），具有光敏性。使用商业试剂进一步检测显示，这种光敏茎通过I型过程。关键是，这种不依赖氧的机制保留了在缺氧条件下产生ROS的能力，克服了肿瘤微环境的限制。在660 nm（0.4 W/cm2）激光照射20 min下，NPs产生ROS，导致90%以上 %的HeLa细胞凋亡，并表现出抗肿瘤作用。体内实验表明，NPs在660 nm激光照射30 min后出现PDT，实现了明显的肿瘤抑制。

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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

Colloids and Surfaces B: Biointerfaces

Pub 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

Esterase-activatable dimeric HDAC inhibitor nanotherapeutics for enhanced lymphoma epigenetic therapy 酯酶活化二聚体HDAC抑制剂纳米疗法用于淋巴瘤表观遗传治疗

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-08 DOI: 10.1016/j.colsurfb.2026.115416

Tongyu Li , Wanchuan Zhuang , Shufang Fan , Ping Yi , Guifang Ouyang , Wenbin Qian

Background

Despite advances in lymphoma therapy, significant challenges persist including R-CHOP resistance and CAR-T toxicity. Hydroxamate-based histone deacetylase inhibitors (HDACi) like vorinostat (SAHA) offer epigenetic therapeutic potential but are limited by poor bioavailability and rapid clearance.

Methods

To overcome these barriers, we rationally designed an esterase- activatable dimeric prodrug by conjugating two SAHA molecules via a glutaric acid linker (SAHA-cc-SAHA). This prodrug co-assembled with DSPE-PEG₂₀₀₀ into nanoparticles (cc-diSAHA NPs). The system was characterized (DLS/TEM), and its drug release profile was assessed with/without porcine liver esterase (PLE). Antitumor activity was evaluated in EL4/A20 lymphoma cells (apoptosis/cycle assays, etc) and EL4 allograft. Transcriptomic mechanisms were deciphered by RNA-seq.

Results

The cc-diSAHA NPs were uniform spheres (∼74 nm, PDI = 0.187) with excellent colloidal stability and minimal drug leakage (<4 % in 7 days), while enabling rapid drug release upon esterase stimulation (92.4 % within 7 h with PLE). In vitro, they demonstrated broad-spectrum anti-lymphoma activity, inducing G₀/G₁ arrest and apoptosis, albeit with delayed kinetics versus free formulations, consistent with a sustained-release profile. Transcriptomics revealed multifaceted mechanisms, including potent activation of interferon-mediated immunogenic stress and hematopoietic differentiation, alongside enriched adhesion and redox metabolism pathways. In vivo, intravenous cc-diSAHA NPs suppressed EL4 tumor growth significantly more than oral SAHA (819.36 vs 1594.40 mm³; p < 0.01), without inducing systemic toxicity or organ damage.

Conclusion

This nanoplatform overcomes HDACi delivery barriers by reconciling the stability-activation paradox, providing a therapeutically viable option for lymphoma patients ineligible for standard intensive therapies.

尽管淋巴瘤治疗取得了进展，但仍存在包括R-CHOP耐药性和CAR-T毒性在内的重大挑战。基于羟酸酯的组蛋白去乙酰化酶抑制剂（HDACi）如伏立诺他（SAHA）具有表观遗传治疗潜力，但受生物利用度差和快速清除的限制。方法通过戊二酸连接剂（SAHA-cc-SAHA）偶联两个SAHA分子，合理设计酯酶活化二聚体前药。该前药与DSPE-PEG2000共组装成纳米颗粒（cc-diSAHA NPs）。采用DLS/TEM对该体系进行了表征，并在添加/不添加猪肝酯酶（PLE）的情况下对其药物释放特性进行了评价。在EL4/A20淋巴瘤细胞（凋亡/周期测定等）和EL4异体移植物中评估抗肿瘤活性。转录组学机制通过RNA-seq破译。结果cc-diSAHA NPs为均匀球体（~ 74 nm, PDI = 0.187），具有良好的胶体稳定性和最小的药物泄漏（7天内漏药率为<；4 %），同时在酯酶刺激下药物释放迅速（PLE在7 h内释放92.4 %）。在体外，它们显示出广谱抗淋巴瘤活性，诱导G0/G1阻滞和细胞凋亡，尽管与游离制剂相比具有延迟动力学，但与缓释特性一致。转录组学揭示了多方面的机制，包括干扰素介导的免疫原性应激和造血分化的有效激活，以及丰富的粘附和氧化还原代谢途径。体内，静脉注射cc-diSAHA NPs对EL4肿瘤生长的抑制作用明显高于口服SAHA (819.36 vs 1594.40 mm³；p <； 0.01)，且未引起全身毒性或器官损伤。结论该纳米平台通过调和稳定性-激活悖论克服了HDACi递送障碍，为不符合标准强化治疗条件的淋巴瘤患者提供了一种治疗可行的选择。

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引用次数: 0

Dental mesenchymal stem cell-derived exosomes for oral diseases: Classification, functionalization and clinical prospects 口腔疾病的牙间充质干细胞来源的外泌体：分类、功能和临床前景。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-08 DOI: 10.1016/j.colsurfb.2026.115431

Yuxuan Teng , Qijing Yang , Yang Zhao , Lingao Zhu , Bingwen Zhong , Bowei Wang , Zhihui Liu

The conventional therapeutic approaches for oral diseases primarily encompass dental restoration, pulp therapy, and maxillofacial surgical interventions. However, these methods are difficult to promote tissue regeneration and immune regulation. Mesenchymal stem cell-derived exosomes (MSC-Exos), mainly derived from tissues such as bone marrow, umbilical cord blood, umbilical cord, placenta, and fat, have been used to study the treatment of oral diseases. Conventional MSCs-Exos have relatively low immunogenicity and ethical issues, but exosomes derived from dental mesenchymal stem cells (DSCs) not only have abundant sources but also lower immunogenicity, which can circumvent ethical restrictions. This review aims to comprehensively investigate the isolation and characterization methods of exosomes derived from dental-derived mesenchymal stem cells (DSC-Exos) as well as their sources and biological properties. It further reviews recent advances in their application within the field of stomatology and summarizes various material-based delivery systems for exosomes. Particular emphasis is placed on their therapeutic potential in inflammatory conditions such as pulpitis, periodontitis, temporomandibular joint disorders, and immune-related diseases, as well as the application prospects of inducing cell directional differentiation in pulp-dentin complex regeneration, jawbone repair, and soft tissue regeneration. In addition, we have reviewed here some possible applications of DSC-Exos to prevent orthodontic relapse and treat oral cancer. The DSC-Exos play multiple roles, including anti-inflammatory activity, immunomodulatory effect, and tissue regeneration, and have a great potential in the clinical treatment of oral inflammation, tissue defects, and immune dysregulation. Their therapeutic efficacy could also be improved by combining them with other biomaterials.

口腔疾病的传统治疗方法主要包括牙齿修复、牙髓治疗和颌面外科干预。然而，这些方法难以促进组织再生和免疫调节。间充质干细胞衍生外泌体（MSC-Exos）主要来源于骨髓、脐带血、脐带、胎盘和脂肪等组织，已被用于研究口腔疾病的治疗。传统的MSCs-Exos具有相对较低的免疫原性和伦理问题，而牙间充质干细胞（dsc）衍生的外泌体不仅来源丰富，而且免疫原性较低，可以规避伦理限制。本文综述了牙源性间充质干细胞（DSC-Exos）外泌体的分离鉴定方法、来源及生物学特性。综述了近年来外泌体在口腔医学领域的应用进展，并总结了各种材料为基础的外泌体递送系统。重点介绍了其在牙髓炎、牙周炎、颞下颌关节紊乱、免疫相关疾病等炎症性疾病中的治疗潜力，以及诱导细胞定向分化在牙髓-牙本质复合体再生、颌骨修复、软组织再生等方面的应用前景。此外，我们还综述了DSC-Exos在预防正畸复发和治疗口腔癌方面的应用前景。DSC-Exos具有抗炎、免疫调节、组织再生等多种作用，在临床治疗口腔炎症、组织缺损、免疫失调等方面具有很大潜力。通过与其他生物材料的结合，还可以提高其治疗效果。

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引用次数: 0

Multifunctional nanozyme-mediated synergistic activation of cuproptosis, ferroptosis, and pyroptosis for potent antitumor therapy 多功能纳米酶介导的铜腐、铁腐和焦腐的协同活化用于有效的抗肿瘤治疗

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2026-01-07 DOI: 10.1016/j.colsurfb.2026.115415

Yuxin Tian , Junfeng Ke , Min Yang , Ping Gong , Fuchen Xin , Liping Wang

Novel forms of programmed cell death are pivotal in regulating tumor progression and therapeutic response; however, single-mode cell death induction often fails to overcome apoptotic escape and drug resistance of tumor cells. This study designed and synthesized a multifunctional nanozyme, ZIF-8/Cu/Fe@GOx (ZCFG), to synergistically inhibit tumor cell growth via cuproptosis/ferroptosis/pyroptosis. Its compensatory mechanisms collectively overcome tumor cell characteristics such as apoptotic escape and drug resistance. Leveraging its multi-enzyme-like activity, ZCFG achieves self-sustained H₂O₂ production, massive glutathione (GSH) depletion, and hydroxyl radical (·OH) bursts to induce tumor cell death. Furthermore, copper and iron ions overload induce metabolic disruption and mitochondrial dysfunction, triggering abnormal aggregation of dihydrolipoamide S-acetyltransferase (DLAT), loss of Fe-S cluster proteins, and accumulation of lipid peroxides to induce cuproptosis and ferroptosis in tumor cells. Notably, the intracellular reactive oxygen species (ROS) bursts and zinc ion overload synergistically activate the caspase-1/GSDMD-dependent pyroptosis pathway, which further amplifies the antitumor effects of cuproptosis and ferroptosis, achieving mutually reinforcing therapeutic effects. This work provides a novel therapeutic strategy for tumor treatment by constructing a cascade-catalyzed nanozyme platform that mediates multimodal synergistic antitumor therapy via cuproptosis, ferroptosis, and pyroptosis.

新形式的程序性细胞死亡是调节肿瘤进展和治疗反应的关键；然而，单模细胞死亡诱导往往不能克服肿瘤细胞的凋亡逃逸和耐药。本研究设计并合成了一种多功能纳米酶ZIF-8/Cu/Fe@GOx (ZCFG)，通过铜腐/铁腐/焦腐协同抑制肿瘤细胞的生长。其代偿机制共同克服了肿瘤细胞的特性，如凋亡逃逸和耐药。利用其多酶样活性，ZCFG实现自我维持的H₂O₂产生，大量谷胱甘肽（GSH）消耗和羟基自由基（·OH）爆发，诱导肿瘤细胞死亡。此外，铜和铁离子过载会导致代谢中断和线粒体功能障碍，引发二氢脂酰胺s -乙酰转移酶（dihydrolipoamide S-acetyltransferase， DLAT）的异常聚集、Fe-S簇蛋白的缺失和脂质过氧化物的积累，从而诱导肿瘤细胞铜下垂和铁下垂。值得注意的是，细胞内活性氧（ROS）爆发和锌离子过载协同激活caspase-1/ gsdmd依赖的焦亡途径，进一步放大了铜腐和铁腐的抗肿瘤作用，实现了相互增强的治疗效果。本研究通过构建一个级联催化的纳米酶平台，通过铜腐、铁腐和焦腐介导多模式协同抗肿瘤治疗，为肿瘤治疗提供了一种新的治疗策略。

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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

Colloids and Surfaces B: Biointerfaces

Pub 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