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Preparation of novel Mn-doped Ti-based organic frameworks for the sonodynamic therapy of serous ovarian carcinoma 新型mn掺杂ti基有机骨架的制备及其在浆液性卵巢癌声动力治疗中的应用
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-26 DOI: 10.1016/j.colsurfb.2025.115318
Shuo Li , Jialu Li , Kun zhang, Jie Zhang, Yuefeng Ji, Zhanfeng Li, Xin Zhou

Abstract

Serous ovarian carcinoma (SOC) is distinguished by marked invasiveness, early dissemination and rapid drug resistance, creating an urgent demand for non‑cross‑resistant alternative therapies. Consequently, the exploration of minimally invasive yet highly effective treatment modalities has become a central research priority. In the present work, a heterobimetallic metal–organic frameworks (MOFs) sonosensitizer, namely Mn‑MX@MIL‑125(Ti), was synthesized by introducing manganese(II) ions into MXene-trussed Ti‑based organic frameworks. The obtained Mn-MX@MIL-125(Ti) exhibited high specific surface area, tunable mesoporous, and abundant metal sites, which collectively conferred excellent catalytic activity. Through a series of tests, it was found that Mn‑MX@MIL‑125(Ti) enhanced the generation of reactive oxygen species (ROS) under low‑intensity ultrasound. For the SK-OV-3 cells, the PEG ylated Mn-MX@MIL-125(Ti) displayed good biocompatibility, but upon ultrasound irradiation, it accomplished half‑maximal inhibitory concentration (IC₅₀) of 27.5 µg mL⁻¹ . And, the pronounced decline in mitochondrial membrane potential indicated that it was the ROS‑mediated mitochondrial damage to effectively curtail tumour proliferation. Besides, in subcutaneous SOC murine model, the tumour‑inhibition rate of 83 % was achieved without discernible systemic toxicity. These results highlight that the Mn-MX@MIL-125(Ti) as a promising bimetallic sonosensitizer is capable of efficiently suppressing the SOC via ultrasound-induced ROS generation.
浆液性卵巢癌(SOC)具有明显的侵袭性、早期传播和快速耐药的特点,迫切需要非交叉耐药的替代疗法。因此,探索微创但高效的治疗方式已成为研究的重点。在本工作中,通过将锰(II)离子引入mxene桁架Ti基有机骨架中,合成了一种杂双金属金属-有机骨架(mof)声敏剂Mn‑MX@MIL‑125(Ti)。所得Mn-MX@MIL-125(Ti)具有高比表面积、介孔可调和丰富的金属位,具有优异的催化活性。通过一系列试验发现,Mn‑MX@MIL‑125(Ti)在低强度超声作用下增强了活性氧(ROS)的生成。对于SK-OV-3细胞,PEG修饰的Mn-MX@MIL-125(Ti)显示出良好的生物相容性,但在超声照射下,它实现了27.5 μ g mL⁻¹ 的一半最大抑制浓度(IC₅₀)。线粒体膜电位的显著下降表明,ROS介导的线粒体损伤有效地抑制了肿瘤的增殖。此外,在皮下SOC小鼠模型中,肿瘤抑制率达到83%,没有明显的全身毒性。这些结果表明Mn-MX@MIL-125(Ti)作为一种有前途的双金属声敏剂能够通过超声诱导ROS的产生有效地抑制SOC。
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引用次数: 0
Tailoring carbon-based nanozymes without metal cofactors: Design principles and applications across therapeutics and sensing 剪裁无金属辅助因子的碳基纳米酶:设计原则和跨治疗和传感的应用
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-25 DOI: 10.1016/j.colsurfb.2025.115316
Sumi Choi , Minjin Kim , Minjeong Kim , Sang Jin Lee , Su-Hwan Kim
Metal-free nanozymes (MFNs), composed of heteroatom-doped carbon frameworks, conductive polymers, and π-conjugated networks, have emerged as versatile enzyme mimics that obviate the toxicity and instability associated with metal-based counterparts. Through the strategic incorporation of nitrogen (N), oxygen (O), sulfur (S), phosphorus (P), iodine (I), and selenium (Se) dopants, alongside the deliberate defect engineering of sp² domains and vacancy sites, these materials replicates superoxide dismutase, glutathione peroxidase, catalase, oxidase, and peroxidase activities under physiological and environmental conditions. This review not only outlines the structural design principles and catalytic mechanisms of MFNs but also presents a comparative analysis with traditional metal-based nanozymes, highlighting differences in catalytic pathways, stability, and biocompatibility. Recent studies are systematically categorized into four major application domains—antioxidant therapeutics, tumor-targeted catalytic therapy, diagnostic and biosensing platforms, antimicrobial systems, and environmental remediation—showcasing representative examples such as biomass-derived carbon dots, polyphenol-functionalized nanoparticles, single-atom catalysts, conductive polyaniline constructs, and photocatalytic carbon nitride. Representative case studies are discussed to elucidate key structure–function relationships and experimentally supported outcomes, encompassing validated in vitro and in vivo findings across antioxidant, therapeutic, and diagnostic systems. This comparative and integrative perspective establishes a cohesive framework for the rational design and translational development of next-generation MFNs.
无金属纳米酶(MFNs)由杂原子掺杂碳框架、导电聚合物和共轭网络组成,是一种多用途的酶模拟物,消除了金属基酶的毒性和不稳定性。通过氮(N)、氧(O)、硫(S)、磷(P)、碘(I)和硒(Se)掺杂剂的策略性掺入,以及sp²结构域和空位的缺陷工程,这些材料可以在生理和环境条件下复制超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶、氧化酶和过氧化物酶的活性。本文综述了MFNs的结构设计原理和催化机理,并与传统金属基纳米酶进行了比较分析,重点介绍了MFNs在催化途径、稳定性和生物相容性方面的差异。最近的研究被系统地分为四个主要的应用领域——抗氧化治疗、肿瘤靶向催化治疗、诊断和生物传感平台、抗菌系统和环境修复——展示了代表性的例子,如生物质衍生的碳点、多酚功能化纳米颗粒、单原子催化剂、导电聚苯胺结构和光催化氮化碳。本文讨论了具有代表性的案例研究,以阐明关键的结构功能关系和实验支持的结果,包括在抗氧化、治疗和诊断系统中验证的体外和体内研究结果。这种比较和综合的视角为下一代mfn的合理设计和转化开发建立了一个有凝聚力的框架。
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引用次数: 0
Advances in hybrid exosome-liposome nanoparticles for enhanced cancer therapy 外泌体-脂质体复合纳米颗粒增强肿瘤治疗的研究进展。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-25 DOI: 10.1016/j.colsurfb.2025.115317
Jinqiu Dou , Jiangye Wang , Guangyuan Zhang , Xiaoge Fu , Yuhang Zhang , Fengying Sun
Exosomes, endogenous nanoscale vesicles secreted by various cell types, have emerged as promising natural carriers for therapeutic delivery due to their excellent biocompatibility, low immunogenicity, prolonged systemic circulation, and intrinsic ability to cross the blood-brain barrier (BBB). They can encapsulate diverse bioactive molecules—including nucleic acids, proteins, and small-molecule drugs—showing great potential in cancer therapy. However, their clinical translation remains hindered by low production yield and limited drug-loading capacity. To overcome these limitations, engineered approaches such as exosome-liposome fusion have been developed. This strategy integrates the biological targeting and membrane stability of exosomes with the tunable physicochemical properties of liposomes, resulting in hybrid exosome-liposome nanoparticles (HELNs) that exhibit improved stability, loading efficiency, and therapeutic performance. This review systematically summarizes the biological characteristics of exosomes from different cellular origins, current methodologies for HELNs fabrication, and their recent advances in drug delivery, gene therapy, and immunotherapy. Finally, the review highlights key advantages of this hybrid strategy for cancer theranostics and discusses ongoing challenges and future perspectives for large-scale production and clinical translation.
外泌体是由各种细胞类型分泌的内源性纳米级囊泡,由于其良好的生物相容性、低免疫原性、延长全身循环和内在的穿越血脑屏障(BBB)的能力,已成为有希望的天然治疗载体。它们可以封装多种生物活性分子,包括核酸、蛋白质和小分子药物,在癌症治疗中显示出巨大的潜力。然而,它们的临床转化仍然受到低产量和有限的载药能力的阻碍。为了克服这些限制,工程方法,如外泌体-脂质体融合已经发展。该策略将外泌体的生物靶向性和膜稳定性与脂质体的可调物理化学特性结合在一起,产生了外泌体-脂质体混合纳米颗粒(HELNs),其稳定性、装载效率和治疗性能都得到了改善。本文系统地综述了不同细胞来源的外泌体的生物学特性、HELNs制备的当前方法以及它们在药物传递、基因治疗和免疫治疗方面的最新进展。最后,综述强调了这种混合策略在癌症治疗中的主要优势,并讨论了大规模生产和临床转化的持续挑战和未来前景。
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引用次数: 0
A losartan-laden thermosensitive hydrogel scaffold to boost tumor chemo-immunotherapy via remodeling tumor mechanical microenvironment 氯沙坦负载的热敏水凝胶支架通过重塑肿瘤机械微环境来促进肿瘤化学免疫治疗。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-25 DOI: 10.1016/j.colsurfb.2025.115314
Hongwei Zhang , Qian Wang , Jiao Li , Jun Zhou , Qiufang Chen
Currently, the groundbreaking progress of immune checkpoint inhibitors has benefited patients with various types of tumors. However, the efficacy of these inhibitors is constrained by the tumor immune-suppressive microenvironment. Furthermore, the hypoxia mediated by intratumoral vascular compression further weakens the anti-tumor immune response within the tumor. Herein, we have meticulously developed a drug-sustained-release scaffold that contains three drug components of oxaliplatin, losartan, and immune checkpoint inhibitor (anti-PD-L1), structured with a thermosensitive hydrogel F127 that can gel in situ upon triggering at body temperature. Oxaliplatin, an effective chemotherapeutic agent, can induce immunogenic cell death in tumor, effectively alleviating the tumor immune-suppressive microenvironment. Meanwhile, losartan potassium, a clinical antihypertensive drug, can reduce tumor stroma, lower tumor solid stress, and relieve intratumoral vascular compression, thereby improving tumor hypoxia. The anti-PD-L1 is a widely used immune checkpoint inhibitor and can precisely block the binding of PD-L1 to PD-1, activating T cell-mediated anti-tumor immune responses. The constructed F127@Oxpt-Los-aPDL1 scaffold triggers a potent anti-tumor immune response, achieving outstanding tumor suppression effects and even induces a powerful abscopal effect, effectively inhibiting the growth of distant tumors. This research presents a novel combination treatment strategy aimed at enhancing the efficacy of immune checkpoint inhibition therapy in stroma-rich tumors.
目前,免疫检查点抑制剂的突破性进展已经使各种类型的肿瘤患者受益。然而,这些抑制剂的疗效受到肿瘤免疫抑制微环境的限制。此外,肿瘤内血管压迫介导的缺氧进一步削弱了肿瘤内的抗肿瘤免疫反应。在此,我们精心开发了一种药物缓释支架,包含奥沙利铂、氯沙坦和免疫检查点抑制剂(抗pd - l1)三种药物成分,结构为热敏水凝胶F127,可在体温触发时原位凝胶。奥沙利铂是一种有效的化疗药物,可诱导肿瘤免疫原性细胞死亡,有效缓解肿瘤免疫抑制性微环境。同时临床降压药物氯沙坦钾可以减少肿瘤间质,降低肿瘤实体应力,缓解肿瘤内血管压迫,从而改善肿瘤缺氧。抗PD-L1是一种广泛使用的免疫检查点抑制剂,可以精确阻断PD-L1与PD-1的结合,激活T细胞介导的抗肿瘤免疫反应。构建的F127@Oxpt-Los-aPDL1支架可触发强效的抗肿瘤免疫反应,达到出色的肿瘤抑制效果,甚至诱导强大的体外效应,有效抑制远处肿瘤的生长。本研究提出了一种新的联合治疗策略,旨在提高免疫检查点抑制治疗富间质肿瘤的疗效。
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引用次数: 0
Antibody orientation drives sensitivity in SARS-CoV-2 detection using dynamic light scattering biosensors 抗体取向驱动动态光散射生物传感器检测SARS-CoV-2的灵敏度
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-25 DOI: 10.1016/j.colsurfb.2025.115292
Camille C. de Mello , Dayenny L. D'Amato , Isabela A.A. Bessa , Mariana C. de Oliveira , Mikaelly O.B. Sousa , Juliana G. Fonseca , Luís Eduardo R. da Cunha , Claudio C. Cirne-Santos , Izabel C. Nunes de P. Paixão , Caroline de S. Barros , Carolina B.P. Ligiero , Célia M. Ronconi
The performance of nanoparticle-based biosensors strongly depends on the orientation and density of immobilized antibodies, yet these parameters remain underexplored in platforms based on dynamic light scattering (DLS). This study investigates how the length of molecular crosslinkers influences antibody orientation, surface coverage, and biosensor sensitivity for SARS-CoV-2 detection. The impact of crosslinker spacer length on the analytical performance of 53 nm-gold nanoparticles (AuNPs) functionalized with polyclonal antibodies (pAb) was evaluated using both the spike protein (S Ptn) and intact viral particles as targets. Biosensors were prepared using carboxylic acid-terminated alkanethiol crosslinkers of varying lengths—3-mercaptopropionic acid (MPA), 6-mercaptohexanoic acid (MHA), and 11-mercaptoundecanoic acid (MUA)—and characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and ultraviolet–visible (UV–Vis) spectroscopy. DLS was used to monitor changes in hydrodynamic diameter (ΔDH) upon antigen binding in artificial saliva. Secondary structure analysis and mathematical fitting using the Hill model were employed to evaluate structural effects and binding cooperativity. MUA-functionalized biosensors showed the best performance, with ΔDH shifts up to 115.2 nm for the S Ptn and 77.76 nm for the virus, with respective limits of detection of 2.96 ng/mL and 1.8 × 10 ³ PFU/mL. These improvements were associated with increased antibody packing and favorable end-on orientation. A Hill coefficient of 2.82 in virus detection indicated positively cooperative binding behavior. This study enhances our understanding of antibody–antigen interactions on nanostructured surfaces and guides the development of more effective DLS-based biosensors.
基于纳米粒子的生物传感器的性能很大程度上取决于固定抗体的方向和密度,然而这些参数在基于动态光散射(DLS)的平台上仍未得到充分的研究。本研究探讨了分子交联剂的长度对检测SARS-CoV-2的抗体取向、表面覆盖率和生物传感器灵敏度的影响。以刺突蛋白(S Ptn)和完整病毒颗粒为靶点,研究了交联剂间隔段长度对多克隆抗体功能化的53纳米金纳米颗粒(AuNPs)分析性能的影响。采用不同长度的羧酸端链烷硫醇交联剂——3-巯基丙酸(MPA)、6-巯基己酸(MHA)和11-巯基癸酸(MUA)制备了生物传感器,并用衰减全反射傅里叶变换红外(ATR-FTIR)光谱和紫外可见(UV-Vis)光谱对传感器进行了表征。DLS用于监测人工唾液中抗原结合后流体动力直径的变化(ΔDH)。采用二级结构分析和Hill模型的数学拟合来评价结构效应和结合协同性。mua功能化的生物传感器表现出最好的性能,S Ptn的ΔDH位移达到115.2 nm,病毒的ΔDH位移达到77.76 nm,检测限分别为2.96 ng/mL和1.8 × 10 ³ PFU/mL。这些改进与增加的抗体包装和有利的端端取向有关。病毒检测的Hill系数为2.82,表明病毒具有积极的协同结合行为。这项研究增强了我们对纳米结构表面上抗体-抗原相互作用的理解,并指导了更有效的基于dls的生物传感器的开发。
{"title":"Antibody orientation drives sensitivity in SARS-CoV-2 detection using dynamic light scattering biosensors","authors":"Camille C. de Mello ,&nbsp;Dayenny L. D'Amato ,&nbsp;Isabela A.A. Bessa ,&nbsp;Mariana C. de Oliveira ,&nbsp;Mikaelly O.B. Sousa ,&nbsp;Juliana G. Fonseca ,&nbsp;Luís Eduardo R. da Cunha ,&nbsp;Claudio C. Cirne-Santos ,&nbsp;Izabel C. Nunes de P. Paixão ,&nbsp;Caroline de S. Barros ,&nbsp;Carolina B.P. Ligiero ,&nbsp;Célia M. Ronconi","doi":"10.1016/j.colsurfb.2025.115292","DOIUrl":"10.1016/j.colsurfb.2025.115292","url":null,"abstract":"<div><div>The performance of nanoparticle-based biosensors strongly depends on the orientation and density of immobilized antibodies, yet these parameters remain underexplored in platforms based on dynamic light scattering (DLS). This study investigates how the length of molecular crosslinkers influences antibody orientation, surface coverage, and biosensor sensitivity for SARS-CoV-2 detection. The impact of crosslinker spacer length on the analytical performance of 53 nm-gold nanoparticles (AuNPs) functionalized with polyclonal antibodies (pAb) was evaluated using both the spike protein (S Ptn) and intact viral particles as targets. Biosensors were prepared using carboxylic acid-terminated alkanethiol crosslinkers of varying lengths—3-mercaptopropionic acid (MPA), 6-mercaptohexanoic acid (MHA), and 11-mercaptoundecanoic acid (MUA)—and characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and ultraviolet–visible (UV–Vis) spectroscopy. DLS was used to monitor changes in hydrodynamic diameter (ΔD<sub>H</sub>) upon antigen binding in artificial saliva. Secondary structure analysis and mathematical fitting using the Hill model were employed to evaluate structural effects and binding cooperativity. MUA-functionalized biosensors showed the best performance, with ΔD<sub>H</sub> shifts up to 115.2 nm for the S Ptn and 77.76 nm for the virus, with respective limits of detection of 2.96 ng/mL and 1.8 × 10 ³ PFU/mL. These improvements were associated with increased antibody packing and favorable end-on orientation. A Hill coefficient of 2.82 in virus detection indicated positively cooperative binding behavior. This study enhances our understanding of antibody–antigen interactions on nanostructured surfaces and guides the development of more effective DLS-based biosensors.</div></div>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":"259 ","pages":"Article 115292"},"PeriodicalIF":5.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mesoscopic-scale insights into cellular internalization of deformable polymeric nanoparticles: Structural heterogeneity vs networked elasticity 可变形聚合物纳米颗粒细胞内化的介观尺度洞察:结构非均质性与网络弹性
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-24 DOI: 10.1016/j.colsurfb.2025.115302
Xianyu Song , Yuxiang Nie , Sijia Wang , Hongchao Liu , Honglai Liu , Shuangliang Zhao
Optimizing nanomaterial properties and functions through modulating physicochemical properties within polymeric nanoparticles (NPs) has been a cornerstone of materials science and bio-nanotechnology. However, this paradigm has yet to be firmly established for broadly defined composite polymeric NPs, where the multiscale structure-function relationships governing bio-nano interactions remain largely unknown. Herein, we cultivated a large-scale mesoscopic simulation to examine the cellular internalization of deformable polymeric NPs with varying structural heterogeneity and networked elasticity. Membrane rupture occurred in homogeneous polymeric NPs with a volume swelling ratio of 5.0–12.5 %, while membrane wrapping was discovered in heterogeneous polymeric NPs during cellular internalization. Heterogeneous architectures with high Young’s modulus resist deformation and induce enhanced rotational membrane perturbations, thereby promoting membrane wrapping and increasing NP uptake. In this case, heterogeneous polymeric NPs, such as core-shell and Janus-shaped NPs, have a 1.7–2.3-fold higher membrane penetration efficiency than homogeneous polymeric NPs. Furthermore, increasing networked elasticity enhances membrane wrapping efficiency by promoting stronger adhesion and resisting structural deformation, as further supported by AFM observations. Importantly, the structural deformation of polymeric NPs impedes cellular internalization via compressed surface adsorption on the membrane; however, this can be compensated for by regulating the internal structural heterogeneity that leads to membrane bending. These findings enhance our understanding of the synergistic influence of structural heterogeneity and networked elasticity on bio-nano interactions, paving the way for the development of more effective nanomaterials for targeted delivery and immune evasion.
通过调节聚合纳米粒子(NPs)的物理化学性质来优化纳米材料的性能和功能已经成为材料科学和生物纳米技术的基石。然而,对于广泛定义的复合聚合物NPs,这种模式尚未牢固建立,其中控制生物纳米相互作用的多尺度结构-功能关系在很大程度上仍然未知。在此,我们培养了一个大规模的介观模拟来研究具有不同结构非均质性和网络弹性的可变形聚合物NPs的细胞内在化。均相聚合物NPs发生膜破裂,体积膨胀率为5.0-12.5 %,而非均相聚合物NPs在细胞内化过程中发现膜包裹。具有高杨氏模量的异质结构抵抗变形并诱导增强的旋转膜扰动,从而促进膜包裹和增加NP摄取。在这种情况下,非均相聚合物NPs(如核-壳和双面形NPs)的膜穿透效率比均相聚合物NPs高1.7 - 2.3倍。此外,网状弹性的增加通过促进更强的附着力和抵抗结构变形来提高膜的包裹效率,AFM观察结果进一步支持了这一点。重要的是,聚合物NPs的结构变形通过膜上的压缩表面吸附阻碍了细胞内化;然而,这可以通过调节导致膜弯曲的内部结构不均匀性来补偿。这些发现增强了我们对结构异质性和网络弹性对生物纳米相互作用的协同影响的理解,为开发更有效的靶向递送和免疫逃避纳米材料铺平了道路。
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引用次数: 0
Bacterial adhesion on glyco-hydrogels: impact of glycan and hydrogel stiffness 细菌在糖-水凝胶上的粘附:聚糖和水凝胶硬度的影响
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-24 DOI: 10.1016/j.colsurfb.2025.115313
Sajani H. Liyanage, Mingdi Yan
Bacterial adhesion on substrate surface is governed by multiple factors, with ligand–bacteria interactions and substrate stiffness among the most important. Using Mycobacterium smegmatis (M. smegmatis) and trehalose as a model system, we synthesized trehalose-functionalized polyacrylamide (Tre-PAAm) of varying stiffness and investigated how trehalose content and substrate stiffness affect the adhesion of M. smegmatis on Tre-PAAm hydrogels. Results show that glycan–bacteria interactions play a more dominant role than substrate stiffness. At 30 % trehalose monomer loading, M. smegmatis adhered more strongly to soft than to hard Tre-PAAm hydrogels. However, this stiffness-dependent effect was reduced at lower trehalose monomer loading, and minimal adhesion was observed on PAAm hydrogels without trehalose. Furthermore, non-complementary glycan–bacterium combinations, e.g., E. coli on Tre-PAAm and M. smegmatis on mannose-functionalized polyacrylamide (Man-PAAm) hydrogels, showed almost no bacterial adhesion regardless of hydrogel stiffnesses. Taken together, these findings demonstrate that specific glycan–bacteria interactions play a dominant role over substrate stiffness in governing bacterial adhesion.
细菌在底物表面的粘附受多种因素的影响,其中配体与细菌的相互作用和底物的硬度是最重要的。以耻垢分枝杆菌(M. smegmatis)和海藻糖为模型体系,合成了不同硬度的海藻糖功能化聚丙烯酰胺(3 - paam),并研究了海藻糖含量和底物硬度对耻垢分枝杆菌在3 - paam水凝胶上粘附的影响。结果表明,聚糖-细菌相互作用比底物硬度起更大的作用。当海藻糖单体负荷为30% %时,耻毛分枝杆菌对软质3 - paam水凝胶的粘附比硬质3 - paam水凝胶的粘附更强。然而,在较低海藻糖单体负载下,这种刚度依赖效应减弱,并且在没有海藻糖的PAAm水凝胶上观察到最小的粘附。此外,非互补的聚糖-细菌组合,如大肠杆菌在3 - paam上,垢垢分枝杆菌在甘露糖功能化的聚丙烯酰胺(Man-PAAm)水凝胶上,无论水凝胶的硬度如何,几乎没有细菌粘附。综上所述,这些发现表明,特定的聚糖-细菌相互作用在控制细菌粘附的底物硬度方面起着主导作用。
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引用次数: 0
A novel graphene oxide–niclosamide hybrid as a potent antiviral agent against dengue virus serotype 3 一种新型氧化石墨烯-氯硝柳胺复合物作为抗3型登革热病毒的有效抗病毒药物
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-22 DOI: 10.1016/j.colsurfb.2025.115304
Pandji Zamzami Fathurrohman , Eko Sri Kunarti , Nastiti Wijayanti , Natsuho Sato , Yoshimasa Amano , Motoi Machida , Sri Juari Santosa
Dengue fever, caused by the dengue virus (DENV), remains a major global health challenge in tropical regions. To date, no officially approved antiviral drug has been specifically targeted at DENV infections. Graphene-based materials, composed of carbon, have demonstrated antiviral potential against various viruses. In this study, graphene oxide-niclosamide (GO-Nic) hybrid material was developed by modifying GO with niclosamide, an antiparasitic anthelmintic drug that has recently shown broad-spectrum antiviral activity, including against DENV. GO was synthesized using the Hummers method and functionalized with niclosamide through a simple mixing process. The antiviral activity of GO-Nic was evaluated in vitro against DENV serotype 3 (DENV-3) using RT-qPCR and indirect immunofluorescence assay, as well as TEM to assess viral morphology and its interaction with GO-Nic. GO-Nic exhibited enhanced antiviral activity of 60.5 % DENV-3 inhibition compared to 47.2 % inhibition of GO. Notably, this GO-Nic antiviral activity was achieved at 200-fold lower concentration compared to unmodified GO. The synergistic effect between GO and niclosamide contributed to the inhibition of viral replication. These findings highlight GO-Nic potential as a novel antiviral candidate for dengue infection.
由登革热病毒(DENV)引起的登革热仍然是热带地区的一个重大全球卫生挑战。迄今为止,还没有正式批准的抗病毒药物专门针对DENV感染。石墨烯基材料,由碳组成,已经证明了对各种病毒的抗病毒潜力。在这项研究中,氧化石墨烯-氯硝柳胺(GO- nic)杂化材料是通过用氯硝柳胺修饰氧化石墨烯而开发的,氯硝柳胺是一种抗寄生虫驱虫药,最近显示出广谱抗病毒活性,包括对DENV的抗病毒活性。采用Hummers法合成氧化石墨烯,并通过简单的混合过程与硝氯胺进行功能化。采用RT-qPCR和间接免疫荧光法评估GO-Nic对DENV血清3型(DENV-3)的体外抗病毒活性,并利用透射电镜(TEM)评估病毒形态及其与GO-Nic的相互作用。GO- nic对DENV-3的抑制率为60.5 %,而GO对DENV-3的抑制率为47.2% %。值得注意的是,与未经修饰的氧化石墨烯相比,这种氧化石墨烯- nic的抗病毒活性在低200倍的浓度下实现。氧化石墨烯和硝氯胺之间的协同作用有助于抑制病毒复制。这些发现突出了GO-Nic作为登革热感染的新型抗病毒候选药物的潜力。
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引用次数: 0
Photo-immunomodulatory multifunctional nanoliposomes targeting myeloid derived suppressor cells augment antitumor immunity for colon cancer 靶向髓源性抑制细胞的光免疫调节多功能纳米脂质体增强结肠癌的抗肿瘤免疫。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-21 DOI: 10.1016/j.colsurfb.2025.115300
Huifang Liu , Sijia Wang , Rong Yang , Fangqing Deng , Yingchun Yang , Xuejing Wang , Lianbing Zhang
The therapeutic effect of cancer immunotherapy is limited by immune resistance caused by the immunosuppressive tumor microenvironment (TME). While photodynamic therapy (PDT) can enhance tumor immunogenicity and initiate anti-tumor immunity, its practical benefits are limited. To address this, we developed a TME-responsive nanoliposome for the co-delivery of the photosensitizer chlorin e6 (Ce6) and the immunomodulatory agent AMD3100. Our results demonstrated that Ce6-mediated PDT effectively induced immunogenic cell death (ICD) in colon cancer cells, as evidenced by the robust surface exposure of calreticulin and the release of high mobility group box 1 (HMGB1). Simultaneously, AMD3100 significantly inhibited the infiltration of myeloid-derived suppressor cells (MDSCs) into the TME by blocking the CXCL12/CXCR4 axis. Combined treatment led to a remarkable 90.2 % inhibition of tumor growth in a murine CT26 colon carcinoma model. This profound antitumor effect was driven by a significant enhancement of dendritic cell (DC) maturation (31.1 %) and a 1.62-fold increase in tumor infiltration of CD8 + T cells, coupled with a 76.11 % reduction in MDSC accumulation. In conclusion, this multifunctional nanoliposome, which synergizes immunogenic PDT with targeted MDSC regulation, presents a highly effective strategy for colon cancer treatment and opens a new avenue for advanced photoimmunotherapy.
免疫抑制肿瘤微环境(TME)引起的免疫抵抗限制了肿瘤免疫治疗的效果。虽然光动力疗法(PDT)可以增强肿瘤免疫原性并启动抗肿瘤免疫,但其实际效益有限。为了解决这个问题,我们开发了一种响应tme的纳米脂质体,用于共同递送光敏剂氯e6 (Ce6)和免疫调节剂AMD3100。我们的研究结果表明,ce6介导的PDT可以有效诱导结肠癌细胞的免疫原性细胞死亡(ICD),这可以通过钙网蛋白的表面暴露和高迁移率组盒1 (HMGB1)的释放来证明。同时,AMD3100通过阻断CXCL12/CXCR4轴显著抑制髓源性抑制细胞(MDSCs)向TME的浸润。在小鼠CT26结肠癌模型中,联合治疗可显著抑制肿瘤生长90.2 %。这种深刻的抗肿瘤作用是由树突状细胞(DC)成熟的显著增强(31.1% %)和CD8 + T细胞肿瘤浸润增加1.62倍以及MDSC积累减少76.11% %驱动的。综上所述,这种协同免疫原性PDT和靶向MDSC调控的多功能纳米脂质体,为结肠癌治疗提供了一种高效的策略,并为先进的光免疫治疗开辟了新的途径。
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引用次数: 0
Platelet membrane-fused and cardiac homing peptide-modified liposomes deliver puerarin to attenuate myocardial ischemia/reperfusion injury by inhibiting pyroptosis 血小板膜融合和心脏归巢肽修饰脂质体通过抑制心肌焦亡来减轻心肌缺血/再灌注损伤。
IF 5.6 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-11-21 DOI: 10.1016/j.colsurfb.2025.115297
Shengnan Li , Guiyong Yang , Ziyi Zhang , Yan Wang , Wenqun Li , Junyong Wu , Qing Du , Zhongbiao Jiang , Xiongbin Hu , Tiantian Tang , Xinyi Liu
To address the critical role of oxidative stress-mediated pyroptosis in myocardial ischemia-reperfusion injury (MI/RI), we developed a novel biomimetic drug delivery system-platelet membrane-fused and cardiac homing peptide-modified liposomes (PUE@CHP/PM-L) which were designed to overcome the clinical limitation of poor myocardial targeting of puerarin (PUE). Fluorescence detection analysis demonstrated that platelet membrane (PM) modification endowed the liposomes with both immune evasion capability and targeting specificity toward ischemic myocardial vasculature, while the cardiac homing peptide (CHP) mediated specific uptake by ischemic cardiomyocytes. Cellular experiments revealed that PUE@CHP/PM-L effectively suppressed NLRP3 inflammasome activation by scavenging ROS, thereby downregulating Caspase-1 activity and GSDMD cleavage, and significantly reducing hypoxia/reoxygenation-induced cardiomyocyte pyroptosis. In vivo imaging confirmed that DiR@CHP/PM-L enhanced drug targeting and retention in ischemic myocardium while markedly reducing hepatic and splenic sequestration. Pharmacological animal studies demonstrated that PUE@CHP/PM-L significantly reduced infarct size, upregulated Connexin 43 expression, improved cardiac function and attenuated myocardial fibrosis by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway. By employing a synergistic targeting strategy, this study successfully overcame the delivery limitations of PUE, enabling the drug to fully exert its pyroptosis-inhibiting effects within ischemic cardiomyocytes, thereby providing a novel approach for the precise treatment of MI/RI.
为了解决氧化应激介导的心肌缺血再灌注损伤(MI/RI)中的关键作用,我们开发了一种新的仿生药物传递系统-血小板膜融合和心脏归家肽修饰脂质体(PUE@CHP/PM-L),旨在克服葛根素(PUE)心肌靶向性差的临床局限性。荧光检测分析表明,血小板膜修饰使脂质体具有免疫逃避能力和对缺血心肌血管的靶向特异性,而心脏归巢肽介导缺血心肌细胞的特异性摄取。细胞实验显示PUE@CHP/PM-L通过清除ROS有效抑制NLRP3炎性体活化,从而下调Caspase-1活性和GSDMD切割,显著减少缺氧/再氧诱导的心肌细胞焦亡。体内成像证实DiR@CHP/PM-L增强了缺血心肌的药物靶向和滞留,同时显著减少肝脏和脾脏的隔离。药理动物研究表明,PUE@CHP/PM-L通过抑制NLRP3/Caspase-1/GSDMD信号通路,显著减小梗死面积,上调Connexin 43表达,改善心功能,减轻心肌纤维化。本研究采用协同靶向策略,成功克服了PUE的给药限制,使该药在缺血心肌细胞内充分发挥其抑制心肌热缩的作用,为MI/RI的精准治疗提供了新的途径。
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Colloids and Surfaces B: Biointerfaces
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