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HRP-crosslinked silk–gelatin bioinks: printability dynamics and modulation of stem cell lineage commitment in 3D bioprinted constructs 酶解交联丝-明胶生物墨水:3D生物打印结构中干细胞谱系承诺的可打印性动力学和调节。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-10 DOI: 10.1039/D6TB00628K
Chandrashish Roy, Priya Banerjee and Sourabh Ghosh

Advancements in 3D bioprinting demand bioinks that demonstrate not only precise printability and mechanical robustness but also consistent biochemical and cellular performance. From previous iterations in our laboratory, a silk fibroin–gelatin (SF–G) bioink was conjugated with mushroom tyrosinase (MT) as the enzymatic crosslinker. However, its clinical translation was hindered by several limitations, including batch-to-batch variation in concentration and enzymatic activity, protracted gelation kinetics, and inconsistent rheological and structural characteristics. To overcome these challenges, we developed a next-generation SF–G bioink employing horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as an alternative enzymatic crosslinking system. This approach facilitated rapid and tunable crosslinking through β-sheet enhancement, yielding hydrogels with improved stiffness, shape fidelity, and resistance to enzymatic degradation. Detailed rheological analysis confirmed optimal shear-thinning behaviour and print fidelity, while reactive oxygen species (ROS) quantification ensured cytocompatibility across physiologically relevant concentrations. Human bone marrow-derived mesenchymal stem cells (hBMSCs) encapsulated within the constructs maintained high viability and demonstrated robust osteogenic and chondrogenic lineage commitment. Furthermore, supplementation with triiodothyronine (T3) and transforming growth factor-β3 (TGF-β3) augmented matrix deposition and tissue-specific morphogenesis. Notably, a 10 U HRP–H2O2 formulation emerged as the most promising candidate, offering a strategic balance of mechanical integrity, bioactivity, and reproducibility. This optimized enzymatic system paves the way for scalable and clinically viable SF–G bioinks tailored for advanced tissue engineering and regenerative medicine applications.

3D生物打印的进步要求生物墨水不仅要具有精确的可打印性和机械稳健性,还要具有一致的生化和细胞性能。根据我们实验室之前的迭代,将丝素-明胶(SF-G)生物链接与蘑菇酪氨酸酶(MT)偶联作为酶交联剂。然而,它的临床转化受到一些限制,包括批间浓度和酶活性的变化,持续的凝胶动力学,以及不一致的流变学和结构特征。为了克服这些挑战,我们开发了下一代SF-G生物链接,使用辣根过氧化物酶(HRP)和过氧化氢(H2O2)作为替代的酶交联系统。这种方法通过β-薄片增强促进了快速和可调的交联,产生的水凝胶具有更高的刚度、形状保真度和抗酶降解性。详细的流变学分析证实了最佳的剪切减薄行为和打印保真度,而活性氧(ROS)量化确保了在生理相关浓度下的细胞相容性。包裹在构建体中的人骨髓源间充质干细胞(hBMSCs)保持了高活力,并表现出强大的成骨和软骨谱系承诺。此外,补充三碘甲状腺原氨酸(T3)和转化生长因子-β3 (TGF-β3)增强了基质沉积和组织特异性形态发生。值得注意的是,10 U的HRP-H2O2配方成为最有希望的候选,提供了机械完整性、生物活性和可重复性的战略平衡。这种优化的酶系统为可扩展和临床可行的SF-G生物墨水铺平了道路,为先进的组织工程和再生医学应用量身定制。
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引用次数: 0
Coordination-driven self-assembly of antioxidative and anti-inflammatory cerium–luteolin nanoparticles for effective treatment of ocular alkali burns 协同驱动的抗氧化和抗炎铈木犀草素纳米颗粒自组装有效治疗眼部碱烧伤。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-09 DOI: 10.1039/D6TB00573J
Chuannan Chen, Jie Yu, Dongni Yao, Yangqi Zhao, Qiao Jin, Yao Liang, Yue Zhao, Yi Dong, Mengyue Xu, Peijin Qiu, Liqun Jin, Chaoyang Hong and Ting Shen

Ocular alkali burns are a severe ophthalmic emergency characterized by excessive production of reactive oxygen species (ROS), persistent inflammation, and corneal neovascularization, often resulting in visual impairment. We develop novel hybrid nanoparticles (CEL NPs) through coordination-driven self-assembly of Ce3+, ε-poly-L-lysine (EPL), and luteolin (Lut) to achieve synergistic ROS scavenging and anti-inflammatory effects. CEL NPs protect human corneal epithelial cells and macrophages from oxidative stress and apoptosis in vitro. CEL NPs also suppress inflammatory responses by inhibiting the NF-κB pathway while activating the Nrf2/HO-1 axis. They exhibit enhanced mucoadhesion and prolonged ocular retention in vivo. In a mouse model of alkali-induced corneal injury, topical CEL NPs markedly accelerate wound closure, reduce neovascularization, attenuate stromal edema, and decrease inflammatory cell infiltration. They outperform the individual components and match the efficacy of dexamethasone, without observable adverse effects. These results demonstrate a safe and effective nanotherapeutic strategy that combines dual redox modulation with anti-inflammatory mechanisms for treating ocular chemical injuries.

眼部碱烧伤是一种严重的眼科急症,其特征是活性氧(ROS)过量产生、持续炎症和角膜新生血管形成,常导致视力损害。我们通过Ce3+、ε-聚l -赖氨酸(EPL)和木犀草素(Lut)的协同自组装,开发了新型杂交纳米颗粒(CEL NPs),以实现协同清除ROS和抗炎作用。CEL NPs在体外保护人角膜上皮细胞和巨噬细胞免受氧化应激和凋亡。CEL NPs还通过抑制NF-κB通路同时激活Nrf2/HO-1轴来抑制炎症反应。它们在体内表现出增强的黏附和延长的眼潴留。在碱性角膜损伤小鼠模型中,外用CEL NPs显著加速创面愈合,减少新生血管形成,减轻基质水肿,减少炎症细胞浸润。它们优于单个成分,与地塞米松的疗效相当,没有可观察到的不良反应。这些结果证明了一种安全有效的纳米治疗策略,该策略结合了双氧化还原调节和抗炎机制来治疗眼部化学损伤。
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引用次数: 0
A shikonin-based self-assembled nanomedicine alleviates DSS-induced colitis involving HDC-associated histamine regulation and gut microbiota modulation 一种基于紫草素的自组装纳米药物缓解dss诱导的结肠炎,涉及hdl相关的组胺调节和肠道微生物群调节。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-08 DOI: 10.1039/D6TB00517A
Wang Zhang, Jingrou Sun, Ying Ou, Jing Zhang, Yilan Bai, Jingxi Hong, Lingchang Meng, Yi Song, Tiepeng Wang, Zhiting Sun and Jing Wu

Ulcerative colitis (UC) is a chronic inflammatory disorder of the intestine characterized by recurrent episodes. Current therapies exhibit limited efficacy and raise safety concerns. This study aimed to enhance the water solubility of the natural compound shikonin and improve its therapeutic efficacy by developing novel metal-phenolic nanoparticles. Zn-shikonin-PEG hybrid nanoparticles (Zn-SHK-PEG NPs) were synthesized by coordinating Zn2+ with shikonin and functionalizing the complex with polyethylene glycol (PEG). Dextran sulfate sodium (DSS)-induced colitis was employed to evaluate the therapeutic potential and mechanisms of the nanoparticles. Treatment with Zn-SHK-PEG NPs markedly alleviated weight loss and colon shortening, decreased the disease activity index (DAI), and reduced histopathological injury. Mechanistic investigations suggested that the nanoparticles reduced histidine decarboxylase (HDC) expression, which was associated with PKM2 regulation, accompanied by decreased histamine (HA) levels and suppressed inflammation. Furthermore, Zn-SHK-PEG NPs altered the gut microbiota composition, including enrichment of Akkermansia muciniphila, which may also contribute to the overall therapeutic effect. In summary, Zn-SHK-PEG NPs ameliorated DSS-induced colitis, and the therapeutic effects were associated with the regulation of the HDC/histamine axis, suppression of inflammatory responses, and modulation of gut microbiota. These findings suggest that Zn-SHK-PEG NPs may represent a potential strategy for ulcerative colitis treatment.

溃疡性结肠炎(UC)是一种以反复发作为特征的肠道慢性炎症性疾病。目前的治疗方法疗效有限,并引起安全问题。本研究旨在通过制备新型金属酚类纳米粒子,提高天然化合物紫草素的水溶性,提高其治疗效果。采用Zn2+与紫草素配位,聚乙二醇(PEG)对配合物进行功能化,合成了Zn-SHK-PEG纳米颗粒(Zn-SHK-PEG NPs)。采用葡聚糖硫酸钠(DSS)诱导的结肠炎来评估纳米颗粒的治疗潜力和机制。用Zn-SHK-PEG NPs治疗可显著缓解体重减轻和结肠缩短,降低疾病活动指数(DAI),减轻组织病理学损伤。机制研究表明,纳米颗粒降低了组氨酸脱羧酶(HDC)的表达,这与PKM2的调节有关,同时降低了组胺(HA)水平,抑制了炎症。此外,Zn-SHK-PEG NPs改变了肠道菌群组成,包括嗜粘阿克曼氏菌的富集,这也可能有助于整体治疗效果。综上所述,Zn-SHK-PEG NPs改善了dss诱导的结肠炎,其治疗效果与HDC/组胺轴的调节、炎症反应的抑制和肠道微生物群的调节有关。这些发现表明,Zn-SHK-PEG NPs可能是治疗溃疡性结肠炎的潜在策略。
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引用次数: 0
From materials to medicine: formulation-driven optimization and clinical prospects of NIR-II optical imaging agents 从材料到医学:NIR-II型光学显像剂配方驱动优化及临床前景
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-08 DOI: 10.1039/D6TB00661B
Junjie Zou, Lijuan Yang, Wenxiang Zhang, Gang Liu and Zhixiang Lu

Conventional optical imaging is constrained by photon absorption and multiple scattering in biological tissues. Extending excitation and emission into the second near-infrared window (NIR-II, 1000–1700 nm) markedly suppresses tissue autofluorescence and improves imaging fidelity. However, enhanced optical performance alone does not ensure clinical translatability. In this review, we distinguish the conceptual boundary between optical probes and translational optical agents, highlighting the critical role of formulation engineering in bridging material functionality with biomedical applicability. Representative NIR-II probe classes are summarized together with their intrinsic advantages and translational limitations. We further discuss key formulation strategies for optical agent construction, including targeting engineering, hydrophilicity regulation, size optimization, and carrier-assisted integration. Recent advances in cardiovascular, oncological, neurological, and multimodal imaging applications are also reviewed. Finally, remaining challenges related to biosafety, imaging hardware, and clinical standardization are discussed. By adopting a formulation-centered perspective, this review emphasizes the transition from signal-generating probes to clinically relevant optical agents and outlines future directions for accelerating the translation of NIR-II imaging toward precision diagnostics and image-guided medicine.

传统的光学成像受到生物组织中光子吸收和多次散射的限制。将激发和发射扩展到第二个近红外窗口(NIR-II, 1000-1700 nm)可显著抑制组织自身荧光并提高成像保真度。然而,仅仅提高光学性能并不能保证临床可翻译性。在这篇综述中,我们区分了光学探针和平移光学试剂之间的概念界限,强调了配方工程在连接材料功能与生物医学适用性方面的关键作用。总结了代表性的NIR-II探针类及其内在优势和翻译局限性。我们进一步讨论了光学试剂构建的关键配方策略,包括靶向工程、亲水性调节、尺寸优化和载波辅助集成。综述了心血管、肿瘤、神经和多模态成像应用的最新进展。最后,讨论了与生物安全、成像硬件和临床标准化相关的剩余挑战。本文采用以配方为中心的观点,强调了从信号产生探针到临床相关光学试剂的转变,并概述了加速NIR-II成像向精确诊断和图像引导医学转变的未来方向。
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引用次数: 0
ApoEVs@FeSe2–RGD as a synergistic redox–immune regulator for accelerating wound healing ApoEVs@FeSe2-RGD作为加速伤口愈合的协同氧化还原免疫调节剂。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-08 DOI: 10.1039/D6TB00418K
Zhen Ma, Minghao Zhou, Juan Tong, Bin Zhu, Jin Liu, Hongbo Wei, Kun Xuan, Xinyu Qiu and Jiang Wang

Wound healing still faces many significant challenges, such as excessive oxidative stress, persistent inflammation and disrupted angiogenesis. To overcome these obstacles, we developed a biomimetic hybrid regulatory platform (ApoEVs@FeSe2–RGD) by anchoring redox-active FeSe2 nanorods onto mesenchymal stem cell-derived apoptotic extracellular vesicles (ApoEVs), followed by surface functionalization with cyclic RGD (cRGD) peptides. This regulator effectively synergizes the robust reactive oxygen species (ROS)-scavenging capacity of FeSe2 with the exceptional biocompatibility of cRGD-functionalized ApoEVs. In vitro assessments revealed that ApoEVs@FeSe2–RGD efficiently cleared abnormally produced ROS to recalibrate the oxidative microenvironment. Consequently, it inhibited pro-inflammatory activation while driving macrophage polarization toward an anti-inflammatory phenotype. The reparative cytokines derived from these reprogrammed macrophages significantly enhanced the migration, proliferation, and angiogenic capacity of endothelial cells. Furthermore, the in vivo assessments in a full-thickness wound healing model demonstrated that this vesicle-scaffolded regulator enhanced the wound closure rate and promoted re-epithelialization, collagen deposition, and neovascularization with good biosafety. Mechanistically, transcriptomic profiling combined with protein validation demonstrated that these therapeutic effects were mediated by the suppression of the NF-κB signaling pathway. Collectively, our study demonstrated that ApoEVs@FeSe2–RGD holds potential as a therapeutic strategy for wound healing by restoring redox homeostasis and orchestrating immune–vascularization coupling for high-quality tissue regeneration.

伤口愈合仍然面临许多重大挑战,如过度氧化应激,持续炎症和血管生成中断。为了克服这些障碍,我们开发了一个仿生混合调节平台(ApoEVs@FeSe2-RGD),通过将氧化还原活性FeSe2纳米棒锚定在间充质干细胞来源的凋亡细胞外囊泡(ApoEVs)上,然后用环RGD (cRGD)肽进行表面功能化。该调节剂有效地将FeSe2强大的活性氧(ROS)清除能力与crgd功能化apoev的卓越生物相容性协同起来。体外评估显示ApoEVs@FeSe2-RGD有效清除异常产生的ROS,重新校准氧化微环境。因此,它抑制促炎激活,同时驱动巨噬细胞向抗炎表型极化。来自这些重编程巨噬细胞的修复细胞因子显著增强了内皮细胞的迁移、增殖和血管生成能力。此外,在全层伤口愈合模型中的体内评估表明,这种囊泡支架调节剂提高了伤口愈合率,促进了再上皮化、胶原沉积和新生血管的形成,具有良好的生物安全性。机制上,转录组学分析结合蛋白验证表明,这些治疗效果是通过抑制NF-κB信号通路介导的。总的来说,我们的研究表明ApoEVs@FeSe2-RGD具有作为伤口愈合治疗策略的潜力,通过恢复氧化还原稳态和协调免疫血管化耦合来实现高质量的组织再生。
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引用次数: 0
An intelligent responsive nanoplatform based on a DNA nanoflowers/Mn:CuS hybrid for targeted and synergistic cancer therapy 基于DNA纳米花/Mn: cu杂交的智能响应纳米平台,用于靶向和协同癌症治疗。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-04 DOI: 10.1039/D5TB02930A
Mengqin Zhang, Yang Wu, Ling Hu, Dongni Pei, Jianxiu Wang and Xinyao Yi

The development of intelligent nanoplatforms that integrate tumor targeting, stimuli-responsive drug release, and multimodal therapy remains a significant challenge for precise cancer treatment. Herein, a nanoplatform based on DNA nanoflowers and Mn:CuS nanoparticles with a unique architecture and multiple therapeutic functions was constructed. The DNA nanoflowers derived from rolling circle amplification (RCA) served as the scaffold, enabling the efficient intercalation of Mn:CuS nanoparticles and doxorubicin (DOX). Furthermore, the sgc-8 aptamer was incorporated into the DNA scaffold for specific recognition of HeLa cells. The intercalated Mn:CuS nanoparticles exhibited photothermal therapeutic activity, peroxidase (POD)/oxidase (OXD)-like properties and glutathione peroxidase (GPx)-like activity, thus achieving amplified therapeutic efficacy toward tumor cells. Moreover, the DOX release was demonstrated to be precisely controllable in acidic environments and under near-infrared (NIR) irradiation, which ensured tumor-specific drug release. Thus, synergistic chemotherapy, photothermal therapy and chemo-dynamic therapy (CDT) of cancers were achieved. Compared with the conventional single-function nanocarriers, this multifunctional hybrid system combines specific target recognition, responsive drug delivery, and multimodal therapeutic treatment, offering a promising avenue for precise and effective cancer therapy.

集成肿瘤靶向、刺激反应性药物释放和多模式治疗的智能纳米平台的发展仍然是精确癌症治疗的重大挑战。在此基础上,构建了基于DNA纳米花和Mn: cu纳米粒子的纳米平台,该平台具有独特的结构和多种治疗功能。通过滚动环扩增(RCA)得到的DNA纳米花作为支架,实现了Mn: cu纳米粒子和阿霉素(DOX)的有效插层。此外,将sgc-8适配体整合到DNA支架中以特异性识别HeLa细胞。嵌入的Mn: cu纳米颗粒表现出光热治疗活性、过氧化物酶(POD)/氧化酶(OXD)样性质和谷胱甘肽过氧化物酶(GPx)样活性,从而增强了对肿瘤细胞的治疗效果。此外,在酸性环境和近红外(NIR)照射下,DOX的释放被证明是精确可控的,从而确保了肿瘤特异性药物的释放。从而实现了肿瘤的协同化疗、光热治疗和化学动力治疗(CDT)。与传统的单一功能纳米载体相比,这种多功能混合系统结合了特异性靶点识别、反应性药物传递和多模式治疗,为精确有效的癌症治疗提供了一条有前景的途径。
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引用次数: 0
Genetically engineered outer membrane vesicles as next-generation bionanomaterials for therapeutic and diagnostic applications 基因工程外膜囊泡作为治疗和诊断应用的下一代生物纳米材料。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-04 DOI: 10.1039/D6TB00650G
Xuyu Bian, Ziyan Huang, Chenhang Xu, Jiawei Yue and Yumin Wu

Outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, represent a unique class of bionanomaterials with inherent immunogenicity, efficient cellular delivery, and scalable production. However, their native toxicity, compositional heterogeneity, and lack of targeting specificity have hindered broader therapeutic translation. Advances in genetic engineering and synthetic biology have revolutionized OMV design, transforming these biological byproducts into highly programmable bionanomaterial platforms. This review systematically outlines the key engineering strategies for OMVs, including surface display for targeting and immunomodulation, cargo loading for encapsulating nucleic acids, proteins, and drugs, and membrane modulation for tuning stability and safety. We highlight the transformative applications of genetically engineered OMVs (geOMVs) in cancer immunotherapy, next-generation vaccines, targeted delivery, and diagnostic imaging. Finally, we discuss the critical challenges in the clinical translation—such as scalable manufacturing, safety profiling, and regulatory pathways—and propose future directions integrating synthetic biology, materials science, and artificial intelligence to realize the full potential of geOMVs as intelligent, precision therapeutic and diagnostic platforms.

外膜囊泡(omv)由革兰氏阴性菌自然释放,是一类独特的生物纳米材料,具有固有的免疫原性、高效的细胞传递和可扩展的生产。然而,它们的天然毒性、成分异质性和缺乏靶向特异性阻碍了更广泛的治疗转化。基因工程和合成生物学的进步彻底改变了OMV的设计,将这些生物副产品转化为高度可编程的生物纳米材料平台。本文系统地概述了omv的关键工程策略,包括用于靶向和免疫调节的表面展示,用于封装核酸、蛋白质和药物的货物装载,以及用于调节稳定性和安全性的膜调节。我们重点介绍了基因工程omv (geomv)在癌症免疫治疗、下一代疫苗、靶向递送和诊断成像方面的变革性应用。最后,我们讨论了临床转化中的关键挑战,如可扩展制造、安全性分析和监管途径,并提出了整合合成生物学、材料科学和人工智能的未来方向,以实现geomv作为智能、精确治疗和诊断平台的全部潜力。
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引用次数: 0
Engineered carbon-based quantum dots: a next-generation nanomedicine for the therapy and diagnosis of infectious diseases 工程碳基量子点:用于治疗和诊断传染病的下一代纳米药物。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-03 DOI: 10.1039/D5TB02755A
Kallol Roy, Esha Roy, Nibedita Saikia, Pankaj Barman, Binoy K. Saikia and Rituraj Konwar

Infectious diseases are a major global health issue despite the development of antibiotics and chemotherapy. There is an unmet need for the development of novel therapeutic and diagnostic agents to combat emerging and multi-drug-resistant microorganisms. To overcome these issues, carbon-based quantum dots (QDs), i.e., carbon quantum dots (CQDs) and graphene quantum dots (GQDs), can be an alternative approach due to their diverse and distinct properties, such as chemical inertness, low toxicity, biocompatibility, and photostability. Engineered QDs (EQDs) prepared by integrating various moieties through doping, functionalization, surface passivation, or combination with antimicrobial substances have vast biological applications in the management of infectious diseases. The current review aims to comprehensively discuss the recent progress on pharmacological mechanisms and detection strategies of native QDs (CQDs and GQDs), and EQDs against a wide range of infectious disease-causing pathogens, namely, bacteria, viruses, fungi, and parasites. The major mechanisms of their action involve cell wall/membrane disruption, replication and transcription inhibition, excessive ROS generation, immune response pathway activation, and synergistic interactions with antimicrobial agents. In addition, EQDs integrated diverse detection strategies, including optical, nucleic acid, immune, lateral flow assay, electrochemistry, emphasizing their potential use as sensitive probes for the rapid monitoring of pathogens in biological and environmental samples. Finally, the evolving scenarios of regulatory requirements, potential toxicity, and challenges in their clinical translation are addressed in this review. The current review will certainly be useful in advancing research activities for developing new affordable antimicrobial drugs and diagnostic agents using native QDs/EQDs.

尽管抗生素和化学疗法得到了发展,但传染病仍然是一个主要的全球健康问题。开发新的治疗和诊断药物以对抗新出现的和多重耐药微生物的需求尚未得到满足。为了克服这些问题,碳基量子点(QDs),即碳量子点(CQDs)和石墨烯量子点(GQDs),由于其多样化和独特的性质,如化学惰性、低毒性、生物相容性和光稳定性,可以成为一种替代方法。通过掺杂、功能化、表面钝化或与抗菌物质联合制备工程化量子点(EQDs),在感染性疾病的治疗中具有广泛的生物学应用。本文综述了近年来天然量子点(CQDs和GQDs)和EQDs对细菌、病毒、真菌和寄生虫等多种感染性病原体的药理学机制和检测策略的研究进展。其作用的主要机制包括细胞壁/膜破坏、复制和转录抑制、过量ROS产生、免疫反应途径激活以及与抗菌药物的协同作用。此外,EQDs整合了多种检测策略,包括光学、核酸、免疫、侧流测定和电化学,强调了它们作为生物和环境样品中病原体快速监测的敏感探针的潜力。最后,本文讨论了其临床转化过程中不断变化的监管要求、潜在毒性和挑战。本文的综述将有助于利用国产量子点/等效量子点开发新的可负担的抗菌药物和诊断药物的研究活动。
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引用次数: 0
Beyond ACE2: unveiling the receptor-mediated endocytic dynamic mechanism of SARS-CoV-2 at the single-particle level 超越ACE2:在单颗粒水平上揭示受体介导的SARS-CoV-2内吞动力学机制
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-03 DOI: 10.1039/D6TB00299D
Xiaoyu Ma, Zhuang Zhang, Dandan Yang, Hui Wang, Hao Zhang, Yue Yang, Siying Li and Yuping Shan

Beyond the canonical angiotensin-converting enzyme 2 (ACE2)-mediated entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells, basigin (BSG) and dipeptidyl peptidase 4 (DPP4) may also act as alternative receptors that can facilitate viral attachment and subsequent endocytosis. Herein, we analyzed the binding efficiency and binding dynamics of SARS-CoV-2 virus-like particles (VLPs), mediated by BSG and DPP4 at the single-particle level, by combining super-resolution direct stochastic optical reconstruction microscopy (dSTORM) and single-molecule force spectroscopy (SMFS). dSTORM imaging demonstrated that DPP4 exhibits higher surface expression levels than BSG on HepG2 cells. However, SARS-CoV-2 VLPs display a distinct preference for BSG-dependent cellular entry. Using SMFS, we further probed the binding dynamics between the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and these two receptors. The results demonstrated that RBD-BSG exhibits greater stability and a more rapid formation rate compared to RBD-DPP4. Subsequently, a real-time force tracing technique was used to show that BSG-mediated VLP entry requires lower force and faster speed compared with DPP4-mediated entry. In particular, we confirmed that the structural integrity of intramolecular disulfide bonds within the RBD is indispensable for mediating high-affinity receptor binding. These findings elucidate the distinct receptor-mediated endocytic dynamic mechanisms underlying SARS-CoV-2 entry mediated by BSG and DPP4, expanding our understanding of viral invasion beyond the ACE2 pathway and providing insights into potential intervention strategies targeting viral infection.

除了典型的血管紧张素转换酶2 (ACE2)介导的严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)进入宿主细胞外,basigin (BSG)和二肽基肽酶4 (DPP4)也可能作为替代受体,促进病毒附着和随后的内吞作用。本研究采用超分辨率直接随机光学重建显微镜(dSTORM)和单分子力谱(SMFS)技术,在单粒子水平上分析了BSG和DPP4介导的SARS-CoV-2病毒样颗粒(VLPs)的结合效率和结合动力学。dSTORM成像显示,DPP4在HepG2细胞上的表面表达水平高于BSG。然而,SARS-CoV-2 VLPs明显倾向于依赖bsg的细胞进入。利用SMFS,我们进一步探讨了SARS-CoV-2刺突蛋白受体结合域(spike - S protein receptor-binding domain, RBD)与这两种受体的结合动力学。结果表明,与RBD-DPP4相比,RBD-BSG具有更高的稳定性和更快的形成速度。随后,采用实时力追踪技术显示,与dpp4介导的进入相比,bsg介导的VLP进入所需的力更小,速度更快。特别是,我们证实了RBD分子内二硫键的结构完整性对于介导高亲和力受体结合是必不可少的。这些发现阐明了BSG和DPP4介导的SARS-CoV-2进入的独特受体介导的内吞动力学机制,扩展了我们对ACE2途径之外的病毒入侵的理解,并为针对病毒感染的潜在干预策略提供了见解。
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引用次数: 0
Poly(glutamic acid-block-tyrosine) peptides designed for gastrointestinal drug adsorption 用于胃肠道药物吸附的聚谷氨酸-阻断酪氨酸肽。
IF 6.2 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-06-02 DOI: 10.1039/D6TB00121A
Hunter B. Wood, Joseph T. Dosch, Stella M. Trickett, Juhi Singh, Farin M. Weinger, Gerald J. Wang, Dazhe J. Cao and Stefanie A. Sydlik

Drug overdose remains a major public health challenge, particularly for non-opioid substances that lack effective antidotes and are often treated through gastrointestinal decontamination with activated charcoal. While activated charcoal is broadly effective, its use is associated with aspiration risks and gastrointestinal complications. Here, we report a class of synthetic poly(glutamic acid-block-tyrosine) (EY) peptide adsorbent materials designed as biocompatible, tuneable alternatives for gastrointestinal drug adsorption. EY polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization with systematically varied tyrosine block lengths to investigate how amino acid composition and length govern adsorption. Adsorption kinetics and capacity were evaluated under simulated gastric (pH 1.2) and intestinal (pH 6.8) conditions for clinically relevant drugs commonly implicated in overdose: amitriptyline (AMI), bupropion (BUP), hydroxychloroquine (HCQ), and strychnine (STR). Increasing tyrosine content enhanced drug uptake, with the top-performing formulation (E30Y129) achieving high adsorption capacities and binding affinities comparable to reported adsorbent biopolymers and competitive with activated charcoal for certain drugs. Langmuir isotherm analysis revealed maximum adsorption capacities of 40–238 mg g−1 and binding affinities up to 0.214 L g−1, with adsorption behavior dependent on drug characteristics. Exploratory fed-state experiments demonstrated that adsorbent properties are retained in the presence of a complex nutrient matrix and vary depending on drug properties. Preliminary enzyme degradation studies indicated gradual proteolysis under gastrointestinal conditions, and cytocompatibility assays with fibroblasts and macrophages showed no overt toxicity across relevant concentrations. Collectively, these results demonstrate that synthetic polypeptides can be engineered to achieve efficient, clinically relevant drug adsorption while offering advantages in biocompatibility, degradability, and tunability. This work establishes a foundation for next-generation gastrointestinal decontamination materials beyond activated charcoal.

药物过量仍然是一个重大的公共卫生挑战,特别是对于缺乏有效解毒剂的非阿片类物质,通常通过活性炭对胃肠道进行净化来治疗。虽然活性炭广泛有效,但其使用与误吸风险和胃肠道并发症有关。在这里,我们报道了一类合成的聚谷氨酸块酪氨酸(EY)肽吸附材料,设计为生物相容性,可调节的胃肠道药物吸附替代品。采用n -羧基氢化开环聚合法制备不同酪氨酸嵌段长度的EY多肽,研究氨基酸组成和长度对吸附的影响。在模拟胃(pH 1.2)和肠道(pH 6.8)条件下,对阿米替林(AMI)、安非他酮(BUP)、羟氯喹(HCQ)和士的宁(STR)等临床相关药物的吸附动力学和容量进行了评估。酪氨酸含量的增加增强了药物的吸收,性能最好的配方(E30Y129)具有高吸附能力和结合亲和力,与报道的吸附剂生物聚合物相当,在某些药物上与活性炭竞争。Langmuir等温线分析表明,吸附量为40 ~ 238 mg g-1,结合亲和度为0.214 L g-1,吸附行为与药物特性有关。探索性实验表明,吸附剂的性质在复杂的营养基质中保持不变,并根据药物性质而变化。初步的酶降解研究表明,在胃肠道条件下,蛋白质会逐渐分解,成纤维细胞和巨噬细胞的细胞相容性实验显示,在相关浓度下,没有明显的毒性。总的来说,这些结果表明,合成多肽可以在生物相容性、可降解性和可调性方面具有优势的同时,实现有效的、临床相关的药物吸附。本研究为开发活性炭以外的下一代胃肠道净化材料奠定了基础。
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Journal of Materials Chemistry B
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