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

Polydimethylsiloxane micropatterning-aided multi-size biomimetic tumor spheroid-on-a-chip for investigating chemotherapy and photodynamic therapy 聚二甲基硅氧烷微图案辅助多尺寸仿生肿瘤球芯片用于化疗和光动力治疗的研究。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-15 DOI: 10.1016/j.colsurfb.2025.115376

Meilin Sun , Jinwei Zhang , Fen Zhang , Zhenghao Deng , Tingting Xuanyuan , Xufang Liu , Danyang Yu , Wenming Liu

Three-dimensional (3D) tumor spheroids are increasingly recognized as promising and prospective models for in vitro cancer research and preclinical screening. However, it remains an unmet need for facile construction of a micro-platform to synchronously produce spheroids with controlled multi-sizes and diverse pathophysiological characteristics for downstream applications. Here, a user-friendly tumor spheroid-on-a-chip system for multi-size biomimetic tumor model fabrication for supporting different antitumor investigations is developed based on the usage of polydimethylsiloxane-micropatterned chip with high fidelity. Simultaneous and massive production of multi-size tumor spheroids with the respective geometric uniformity is achieved on the simple-to-operate chips. The fabricated multi-size spheroids possess multiple native tumor-like features including complicated multilayer arrangement, multiple phenotypical/biochemical gradients, and various microenvironmental molecule and stroma compositions. The applicability of the system in throughput and multi-parallel investigation of multi-size tumor responses to both chemotherapy and photodynamic therapy is experimentally validated too. The size control of tumor models and their biomimetic degree are proved to be important for identifying drug susceptibility and resistance during the antitumor therapy evaluation. This microengineering advancement has potential applications in oncology, drug development, and tissue engineering and provides an insight into the development of the accessible and generalizable microplatform for cancer research.

三维（3D）肿瘤球体越来越被认为是体外癌症研究和临床前筛查的有前途和前瞻性的模型。然而，为了下游应用，快速构建一个微平台来同步生产具有多种尺寸和多种病理生理特征的球体，仍然是一个未满足的需求。本文基于高保真度聚二甲基硅氧烷微图芯片，开发了一种用户友好的肿瘤球片系统，用于多尺寸仿生肿瘤模型的制作，以支持不同的抗肿瘤研究。在操作简单的芯片上实现了多尺寸肿瘤球体的同时和批量生产，并具有各自的几何均匀性。制备的多尺寸球体具有多种天然肿瘤样特征，包括复杂的多层排列，多种表型/生化梯度以及多种微环境分子和基质组成。实验也验证了该系统在多尺寸肿瘤对化疗和光动力治疗反应的通量和多平行研究中的适用性。在抗肿瘤治疗评价中，肿瘤模型的大小控制及其仿生程度对确定药物敏感性和耐药性具有重要意义。这一微工程进展在肿瘤学、药物开发和组织工程方面具有潜在的应用前景，并为癌症研究提供了一个可访问和可推广的微平台。

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引用次数: 0

Multifunctional scaffold integrating chemo/photothermal therapy and bone defect reconstruction for osteosarcoma: An in vitro evaluation 结合化疗/光热疗法和骨缺损重建的骨肉瘤多功能支架：体外评估。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-13 DOI: 10.1016/j.colsurfb.2025.115369

Yulong Jin , Ying Yue , Quan Li , Kai Tang , Yongmin Mao , Kai Wang , Aiguo Zhang

Osteosarcoma (OS) represents the most common malignant bone tumor in adolescents. The current standard-of-care regimen combines preoperative induction chemotherapy, radical surgical resection, and postoperative consolidative chemotherapy. Emerging evidence indicates that near-infrared (NIR) light-induced hyperthermia exhibits dual therapeutic effects by inducing tumor cell apoptosis and stimulating osteogenic differentiation. Polydopamine (PDA) converts NIR light into localized heat, enabling scaffold functionalization and drug conjugation via its reactive surface. Doxorubicin (DOX) forms stable π-π stacking complexes with PDA, creating a versatile chemotherapeutic delivery platform. Biphasic calcium phosphate (BCP), whose composition closely resembles natural bone mineral, exhibits excellent biocompatibility and tunable bioactivity through phase ratio modulation. While 3D-printed BCP scaffolds offer precise geometric control, their inherent osteoinductive potential remains suboptimal. Integration of bone morphogenetic protein-2 (BMP2) through surface biofunctionalization represents a promising strategy to enhance scaffold bioactivity, though conventional BMP2 delivery systems suffer from initial burst release and dose-dependent complications. Heparin/polyethyleneimine (PEI) nanogels provide an elegant solution through BMP2 encapsulation, enabling sustained release kinetics and reduced systemic toxicity. This study proposes the development of a multifunctional scaffold system for synergistic chemo-photothermal therapy and bone regeneration in OS treatment. The design incorporates a DOX-conjugated PDA coating to anchor BMP2-loaded nanogels onto BCP scaffolds, achieving spatially controlled drug delivery and localized hyperthermia. We hypothesize that this integrated approach will demonstrate enhanced antitumor efficacy while promoting functional bone reconstruction. Comprehensive in vitro evaluations will elucidate the underlying mechanisms and provide preclinical validation for this precision oncology strategy.

骨肉瘤（Osteosarcoma， OS）是青少年最常见的恶性骨肿瘤。目前的标准治疗方案包括术前诱导化疗、根治性手术切除和术后巩固化疗。越来越多的证据表明，近红外（NIR）光诱导热疗具有诱导肿瘤细胞凋亡和刺激成骨分化的双重治疗作用。聚多巴胺（PDA）将近红外光转化为局部热，通过其活性表面实现支架功能化和药物偶联。阿霉素（DOX）与PDA形成稳定的π-π堆叠复合物，创造了一个多功能的化疗递送平台。双相磷酸钙（BCP）具有良好的生物相容性和可调节的生物活性，其组成与天然骨矿物质非常相似。虽然3d打印的BCP支架提供了精确的几何控制，但其固有的骨诱导潜力仍然不理想。骨形态发生蛋白-2 （BMP2）通过表面生物功能化的整合是增强支架生物活性的一种有前景的策略，尽管传统的BMP2递送系统存在初始爆裂释放和剂量依赖性并发症。肝素/聚乙烯亚胺（PEI）纳米凝胶通过BMP2包封提供了一种优雅的解决方案，实现了缓释动力学和降低了全身毒性。本研究提出了一种多功能支架系统的发展，用于骨肉瘤治疗中的协同化学光热治疗和骨再生。该设计结合了dox -共轭PDA涂层，将装载bmp2的纳米凝胶固定在BCP支架上，实现了空间控制的药物输送和局部热疗。我们假设这种综合方法将在促进功能性骨重建的同时显示出增强的抗肿瘤功效。全面的体外评估将阐明潜在的机制，并为这种精确的肿瘤学策略提供临床前验证。

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引用次数: 0

Transformative progress of SPIONs in cancer theranostics: A comprehensive review on recent advances in SPIONs technology SPIONs在癌症治疗中的革命性进展：SPIONs技术最新进展的综合综述。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-13 DOI: 10.1016/j.colsurfb.2025.115372

Gourang Hari Gupta , Khyati Parmar , Sumanta Ghosh , Simran Gupta , Vijay Aherwar , Shreya Kadam , Saichand Thakkellapati , Mounika Choppadandi , K. Srinivasa Rao , Sarath Babu Srivalliputtur , Govinda Kapusetti

To explore the fundamental properties and biomedical potential of Superparamagnetic Iron Oxide Nanoparticles (SPIONs), a multidisciplinary approach involving chemists, physicists, and material scientists is essential. This review highlights the unique magnetic properties of SPIONs compared to bulk magnetic materials, alongside their synthesis, characterization methods, and the factors influencing their magnetic behavior. We delve into the diverse biomedical applications of SPIONs, including their roles as contrast agents in imaging, drug carriers, and therapeutic agents for cancer treatment. Special attention is given to the concept of theranostics, where SPIONs are utilized for both therapy and diagnosis within a single system. We comprehensively summarize recent advances in the use of SPIONs for cancer theranostics over the past decade while briefly addressing their toxicity and biodegradability. Finally, the review discusses the current challenges and future prospects of SPIONs in theranostic applications including its explorations in ongoing clinical trials. The current study addresses the challenges and future perspectives in applying SPIONs in oncology, providing a roadmap for future research and development. Furthermore, considering the potential of SPION-based therapeutic platforms to achieve targeted anticancer efficacy, this article is expected to make a significant contribution to the existing body of knowledge and inspire further advancements in this rapidly evolving field.

为了探索超顺磁性氧化铁纳米颗粒（SPIONs）的基本特性和生物医学潜力，化学家、物理学家和材料科学家必须采用多学科方法。本文综述了SPIONs与块状磁性材料相比的独特磁性，以及它们的合成、表征方法和影响其磁性行为的因素。我们深入研究了SPIONs在生物医学上的各种应用，包括它们在成像、药物载体和癌症治疗中的造影剂作用。特别注意的是治疗学的概念，其中SPIONs被用于治疗和诊断在一个单一的系统。我们全面总结了近十年来SPIONs用于癌症治疗的最新进展，同时简要介绍了它们的毒性和生物降解性。最后，综述讨论了SPIONs在治疗应用中的挑战和未来前景，包括其在正在进行的临床试验中的探索。目前的研究解决了SPIONs在肿瘤学中应用的挑战和未来前景，为未来的研究和发展提供了路线图。此外，考虑到基于spon的治疗平台在实现靶向抗癌功效方面的潜力，本文有望对现有知识体系做出重大贡献，并激发这一快速发展领域的进一步发展。

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引用次数: 0

Frankincense-loaded lactoferrin-conjugated solid lipid nanoparticles for targeted brain delivery and neuroprotection in a scopolamine-induced Alzheimer’s model 乳香负载的乳铁蛋白结合固体脂质纳米颗粒在东莨菪碱诱导的阿尔茨海默病模型中的靶向脑递送和神经保护

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-13 DOI: 10.1016/j.colsurfb.2025.115370

Farimah Moazzam , Ashrafalsadat Hatamian-Zarmi , Marzie Sabaghian , Khadijeh Khezri , Bahman Ebrahimi Hosseinzadeh , Fariba Khodagholi , Moloud Jalili Shahmansouri , Fatemeh Sadat Rashidi

Central nervous system (CNS) disorders remain a major field with substantial unmet therapeutic needs. This study aimed to address the critical challenge of brain drug delivery by employing solid lipid nanoparticles (SLNs) surface-functionalized with lactoferrin (Lf) ligands, from the transferrin family, to facilitate transport across the blood–brain barrier. Frankincense (F), a natural compound with well-documented neuroprotective properties and minimal adverse effects, was encapsulated within (SLNs) using a microemulsion approach. The optimal formulation resulted in nanoparticles (NPs) with an average size of 103.1 ± 0.9 nm, an encapsulation efficiency of 95.2 ± 0.8 %, a drug loading capacity of 8.6 ± 0.1 %, a polydispersity index (PDI) of 0.3 ± 0.08, and a zeta potential of −29.2 ± 0.5 mV. The optimized NPs showed a sustained drug release profile, and ATR-FTIR spectra confirmed the conjugation of lactoferrin to the nanoparticles. To establish translational relevance, the neuroprotective effectiveness of (F-Lf-SLNs) was investigated using a scopolamine-induced Alzheimer's disease animal model. Behavioral tests, along with biochemical and histological analyses, were conducted. The findings demonstrated that (F-Lf-SLNs) significantly improved the brain delivery of frankincense, highlighting their promise as a neuroprotective strategy for CNS disorders. They also effectively protected neurons compared to the scopolamine-induced group. Overall, these results emphasize the key role of drug delivery systems and ligand-targeting methods in enhancing the therapeutic effectiveness of drugs.

中枢神经系统（CNS）疾病仍然是一个主要的领域，有大量未满足的治疗需求。本研究旨在通过使用固体脂质纳米颗粒（sln）表面功能化乳铁蛋白（Lf）配体（来自转铁蛋白家族）来促进通过血脑屏障的运输，从而解决脑药物递送的关键挑战。乳香(F)是一种天然化合物，具有充分证明的神经保护特性和最小的不良反应，使用微乳液方法包被在（sln）内。最优配方导致纳米颗粒(NPs)平均大小103.1 ±0.9 nm,封装效率95.2 ±0.8 %,药物负荷容量8.6 ±0.1 %,多分散性指数(PDI) 0.3±0.08,和29.2−的电动电势 ±0.5 mV。优化后的纳米颗粒具有持续的药物释放特性，ATR-FTIR光谱证实了乳铁蛋白与纳米颗粒的结合。为了建立翻译相关性，使用东莨菪碱诱导的阿尔茨海默病动物模型研究了（f- lf - sln）的神经保护作用。进行了行为学测试以及生化和组织学分析。研究结果表明，（f- lf - sln）显著改善了乳香的大脑递送，突出了它们作为中枢神经系统疾病的神经保护策略的前景。与东莨菪碱诱导组相比，它们还能有效地保护神经元。总之，这些结果强调了药物传递系统和配体靶向方法在提高药物治疗效果方面的关键作用。

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引用次数: 0

Ultrafast laser synthesis of NIR-absorbing Au-TiO2 nanoagents for photothermal theranostics 光热治疗用nir吸收型Au-TiO2纳米试剂的超快激光合成。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-12 DOI: 10.1016/j.colsurfb.2025.115359

Andrey Amosov , Stanislav O. Gurbatov , Aleksandr V. Shevlyagin , Andrei Pilnik , Evgeny Modin , Soslan Khubezhov , Ekaterina S. Menchinskaya , Tatiana Yu. Gorpenchenko , Dmitry L. Aminin , Aleksandr A. Kuchmizhak

Pure noble metal nanoparticles (NPs) are widely used as benchmarks in theranostic applications, such as photothermal cancer therapy. However, plasmon-mediated absorption of such NPs is typically confined to the visible range, resulting in poor light-to-heat conversion efficiency within the near-infrared (NIR) wavelengths matching biological transparency windows. Here, we report a rapid, single-step synthesis of NIR-absorbing Au-TiO₂ nanocomposites through femtosecond-laser modification of a commercial anatase TiO₂ nanopowder (P25) suspension containing tetrachloroauric acid. High-repetition-rate ultrashort laser irradiation yields, within minutes, core-satellite nanostructures (<100 nm) comprising an amorphous titania core decorated with Au nanoclusters. Comprehensive characterization confirms laser-induced modifications, which endow the product with strong NIR absorption in the first biological transparency window. Au-TiO₂ NPs exhibit a competitive photothermal conversion efficiency at low concentrations down to 10 μg/mL, low in vitro toxicity comparable to pristine P25 TiO₂ NPs, and efficient uptake by triple-negative breast cancer cells. Additionally, the nanocomposites demonstrate a drug-carrying capacity and compatibility with bio-visualizing molecules, highlighting their potential as a novel nanoagent for anticancer theranostics.

纯贵金属纳米颗粒（NPs）被广泛用作治疗应用的基准，例如光热癌症治疗。然而，等离子体介导的这种NPs的吸收通常局限于可见光范围，导致在与生物透明窗口匹配的近红外（NIR）波长内光热转换效率较差。在这里，我们报道了通过飞秒激光修饰含有四氯金酸的商业锐钛矿型TiO2纳米粉末（P25）悬浮液，快速、单步合成nir吸收型Au-TiO2纳米复合材料。在高重复率的超短激光照射下，在几分钟内，核心-卫星纳米结构（2nps）在低浓度（低至10 μg/mL）下表现出具有竞争力的光热转换效率，体外毒性与原始P25 TiO2 NPs相当，并且被三阴性乳腺癌细胞有效吸收。此外，纳米复合材料显示出药物携带能力和与生物可视化分子的相容性，突出了它们作为抗癌治疗的新型纳米剂的潜力。

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引用次数: 0

Cu-doped HA coating with osteogenic and antimicrobial properties on porous tantalum 多孔钽上具有成骨和抗菌性能的掺铜透明质酸涂层

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-12 DOI: 10.1016/j.colsurfb.2025.115371

Yue Qiang , Xun Qi , Wentao Liu , Shenshen Wu , Xi Li , Miao Li

Porous tantalum (Ta) implants have exhibited exceptional clinical performance in bone defect reconstruction for several decades. However, the poor osseointegration and antibacterial capability of unmodified Ta implants restrict their broader clinical application. This study presents an innovative composite material fabricated via hydrothermal synthesis: Cu-doped hydroxyapatite (HA) coatings applied to Ta substrates (designated as HA-xCu, where x = 1, 3, or 5 wt%). In vitro results indicated that the composites had good biocompatibility, bone integration, and antibacterial properties. Cu incorporation promoted the release of Cu²⁺ and Ca²⁺, which contributed to bactericidal effects by inducing the production of reactive oxygen species (ROS), increasing intracellular malondialdehyde (MDA) levels, and enhancing catalase (CAT) activity. Simultaneously, the composites upregulated the expression of osteogenesis-related genes, as confirmed by increased alkaline phosphatase (ALP) activity and positive Alizarin Red Staining (ARS) results. RNA sequencing and western blot analysis revealed that HA-5Cu activated the MAPK signaling pathway to promote osteogenesis. In vivo experiments further demonstrated that HA-5Cu accelerated infection healing and promoted bone regeneration, thereby exhibiting synergistic antibacterial and osteogenic effects. These findings underscore the promising potential of Ta-based implants to meet antimicrobial and osseointegration requirements in clinical orthopedic applications.

几十年来，多孔钽（Ta）植入物在骨缺损重建中表现出优异的临床性能。然而，未经改性的Ta种植体骨整合能力差，抗菌能力差，限制了其广泛的临床应用。本研究提出了一种通过水热合成的创新复合材料：将cu掺杂羟基磷灰石（HA）涂层应用于Ta衬底（指定为HA- xcu，其中x = 1,3或5 wt%）。体外实验结果表明，复合材料具有良好的生物相容性、骨整合性和抗菌性能。Cu的掺入促进了Cu2+和Ca2+的释放，从而通过诱导活性氧（ROS）的产生、增加细胞内丙二醛（MDA）水平和增强过氧化氢酶（CAT）活性来达到杀菌作用。同时，复合材料上调了成骨相关基因的表达，碱性磷酸酶（ALP）活性和茜素红染色（ARS）阳性结果证实了这一点。RNA测序和western blot分析显示HA-5Cu激活MAPK信号通路促进成骨。体内实验进一步证明HA-5Cu能加速感染愈合，促进骨再生，具有协同抗菌和成骨作用。这些发现强调了ta基种植体在临床骨科应用中满足抗菌和骨整合要求的巨大潜力。

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引用次数: 0

One-pot integration of functional molecules into polyphenol-peptide supramolecular self-assembly coatings with diverse and customizable functionalities 一锅集成功能分子到多酚肽超分子自组装涂料具有多样化和可定制的功能。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-11 DOI: 10.1016/j.colsurfb.2025.115361

Hongxiang Wang , Kaiyuan Huo , Feijing Hao , Xingjie Zan , Guangyu Zhang , Na Li

The customizability of coating functionalities is essential for the diverse applications of modern medical devices. Supramolecular self-assembled (SSA) coatings provide distinct advantages over traditional chemically modified coatings but are often hindered by challenges in functionalization. Here, we present a novel, simple, and effective strategy for functionalizing SSA coatings composed of hexameric arginine (Arg6) and tannic acid (TA) through the incorporation of functional molecules. By exploiting the abundant phenolic hydroxyl interactions in TA, various functional molecules are employed and seamlessly integrated into Arg6-TA SSA coatings via a one-pot method, yielding highly customizable functionalities, including antifouling (via hydrogen bonding with PEG), enhanced cell adhesion (via π-π stacking with cRGD), improved bone differentiation (via coordination to Sr^2 + ion), and antimicrobial activity (via electrostatic interactions with TOB). The underlying interaction mechanisms were thoroughly investigated, and the functional properties and stability of the coatings were validated. This approach provides a promising pathway for expanding the application of SSA coatings and advancing functionalization techniques.

涂层功能的可定制性对于现代医疗设备的各种应用至关重要。超分子自组装（SSA）涂料与传统的化学改性涂料相比具有明显的优势，但在功能化方面经常受到挑战。在这里，我们提出了一种新颖、简单、有效的策略，通过加入功能分子来实现六聚精氨酸（Arg6）和单宁酸（TA）组成的SSA涂层的功能化。通过利用TA中丰富的酚羟基相互作用，通过一锅方法将各种功能分子无缝集成到Arg6-TA SSA涂层中，产生高度可定制的功能，包括防污（通过与PEG的氢键结合），增强细胞粘附（通过与cRGD的π-π堆叠），改善骨分化（通过与Sr2 +离子协调）和抗菌活性（通过与TOB的静电相互作用）。深入研究了其相互作用机理，并验证了涂层的功能性能和稳定性。该方法为扩大SSA涂层的应用范围和推进功能化技术的发展提供了一条有前景的途径。

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引用次数: 0

A hydroxylated collagen-like construct with an integrin-binding motif produced in a probiotic chassis: Synthesis, structural stability, and in-vitro bioactivity 在益生菌基质中产生的具有整合素结合基序的羟基化胶原样结构：合成、结构稳定性和体外生物活性

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-11 DOI: 10.1016/j.colsurfb.2025.115368

Zheng Zhang , Jing Zhang , Lihui Zheng , Wenjing Zhao , Tanglin Liu , Jiajing Wu , Wei Su , Yuchen Huang , Shijing Luo , Cong Wang , Mingfei Jin , Jing Huang

Recombinant production of collagen in Escherichia coli is pivotal for advancing biomedical applications, yet it is frequently hampered by critical challenges, notably endotoxin contamination and insufficient prolyl hydroxylation. To address these limitations, we engineered the probiotic bacterium E. coli Nissle 1917 (EcN) as a chassis for producing a hydroxylated human type III collagen-like protein named R8. Through the co-expression of R8 with Bacillus anthracis prolyl 4-hydroxylase (BaP4H) in EcN, we achieved a yield of 0.26 mg/mL for the hydroxylated collagen. A hydroxylation rate of 60 % was achieved, with LC–MS/MS mapping confirming modification at 33 out of 65 proline residues. Hydroxylated R8 exhibits enhanced thermal stability, maintaining the structural integrity of its triple helix and assembling into a porous fibrous network. Crucially, R8 from EcN showed reduced immunogenicity in macrophage activation assays, in stark contrast to material from conventional E. coli BL21(DE3). Moreover, hydroxylated R8 exhibits excellent biocompatibility, significantly promoting fibroblast proliferation and migration, and underscoring the critical role of this modification. This study establishes a strategy for producing bioactive collagen, whilst highlighting the critical importance of hydroxylation for collagen stability and function.

在大肠杆菌中重组生产胶原蛋白对于推进生物医学应用至关重要，但它经常受到严重挑战的阻碍，特别是内毒素污染和脯氨酰羟基化不足。为了解决这些限制，我们设计了益生菌大肠杆菌Nissle 1917 （EcN）作为生产羟基化人类III型胶原样蛋白R8的基础。通过R8与炭疽芽孢杆菌脯氨酸4-羟化酶（BaP4H）在EcN中的共表达，我们获得了羟基化胶原的产率为0.26 mg/mL。羟基化率达到60 %，LC-MS /MS图谱确认在65个脯氨酸残基中有33个被修饰。羟基化R8表现出增强的热稳定性，保持其三螺旋结构的完整性，并组装成多孔纤维网络。关键是，与传统大肠杆菌BL21（DE3）材料形成鲜明对比，EcN中的R8在巨噬细胞激活试验中显示出降低的免疫原性。此外，羟基化R8表现出良好的生物相容性，显著促进成纤维细胞的增殖和迁移，强调了这种修饰的关键作用。本研究建立了一种生产生物活性胶原蛋白的策略，同时强调了羟基化对胶原蛋白稳定性和功能的关键重要性。

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引用次数: 0

A H2O2-self-supplying and oxygen-evolving nanosystem for amplified chemodynamic therapy of breast cancer 用于乳腺癌强化化疗动力学治疗的h2o2自供氧纳米系统

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-11 DOI: 10.1016/j.colsurfb.2025.115363

Yijun Wu , Longxia Li , Lechen Jia , Mingyang Wang , Wenjing Li , Yihong Ma , Xiaochen Wang , Chaoqun Liu

Breast cancer continues to be a prevalent malignancy with high incidence and mortality rates worldwide, urgently calling for more effective treatment options. Chemodynamic therapy (CDT) has gained attention as a novel cancer treatment modality; however, its therapeutic outcome is severely compromised by insufficient intratumoral hydrogen peroxide (H₂O₂), hypoxia conditions, and the glutathione (GSH)-mediated antioxidant defense mechanism. To address these limitations, we developed a multifunctional nanosystem (denoted as HML) composed of hyaluronic acid-coated hollow manganese dioxide nanoparticles loaded with β-lapachone (β-LAP). Upon targeted accumulation at the tumor site, the HML nanoparticles disassemble within acidic and GSH-enriched tumor milieu, triggering the synchronous release of Mn²⁺ and β-LAP. This process effectively depletes GSH and generates oxygen in situ to ameliorate tumor hypoxia. Importantly, the released β-LAP acts as an endogenous H₂O₂ generator, ensuring a continuous supply that is catalyzed by Mn²⁺ via Fenton-like reactions to yield extremely cytotoxic hydroxyl radicals. This results in a lethal burst of oxidative stress and robust apoptosis of tumor cells. Extensive in vitro and in vivo evaluations confirmed the HML nanosystem achieves potent tumor suppression with minimal adverse effects. Overall, this study presents an efficient therapeutic approach for enhancing CDT by simultaneously addressing multiple biological barriers.

乳腺癌仍然是世界范围内发病率和死亡率高的普遍恶性肿瘤，迫切需要更有效的治疗方案。化学动力疗法（CDT）作为一种新的癌症治疗方式受到了广泛关注。然而，肿瘤内过氧化氢（H2O2）不足、缺氧条件和谷胱甘肽（GSH）介导的抗氧化防御机制严重影响其治疗效果。为了解决这些限制，我们开发了一种多功能纳米系统（标记为HML），该系统由透明质酸包覆的中空二氧化锰纳米颗粒组成，并装载了β-lapachone （β-LAP）。HML纳米颗粒在肿瘤部位靶向积累后，在酸性和富含gsh的肿瘤环境中分解，触发Mn2+和β-LAP的同步释放。这个过程有效地消耗谷胱甘肽，并在原位产生氧气，以改善肿瘤缺氧。重要的是，释放的β-LAP作为内源性H2O2发生器，确保持续供应，由Mn2+通过芬顿样反应催化产生极具细胞毒性的羟基自由基。这导致了致命的氧化应激爆发和肿瘤细胞的强大凋亡。广泛的体外和体内评估证实，HML纳米系统具有有效的肿瘤抑制作用，且副作用最小。总的来说，本研究提出了一种通过同时处理多种生物屏障来增强CDT的有效治疗方法。

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引用次数: 0

Polydopamine-modified cyclodextrin metal-organic framework for efficient BCL-2 siRNA delivery in lung cancer therapy 肺癌治疗中高效BCL-2 siRNA递送的聚多巴胺修饰环糊精金属-有机框架

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces

Pub Date : 2025-12-11 DOI: 10.1016/j.colsurfb.2025.115365

Yu Sun , Rongxin Guo , Hongbin Xu , Ziwei Jing , Qiuzheng Du , Feifei Chen , Yaping He

The antiapoptotic protein B-cell lymphoma 2 (BCL-2) is overexpressed in lung cancer, serving as a key mechanism for apoptosis evasion. Therapeutics targeting BCL-2, such as small interfering RNA (siRNA), hold great promise for lung cancer treatment, while delivery challenges hinder the clinical applications of BCL-2 targeting agents. Cyclodextrin metal-organic framework (CD-MOF) is a facile and edible drug delivery carrier with remarkable biocompatibility, which is a suitable candidate for gene delivery. In our study, BCL-2 siRNA (siBCL-2) was loaded into CD-MOFs and subsequently coated by polydopamine (PDA) to form siBCL-2@CD-MOF@PDA nanoplatform. PDA modification creates a protective layer, preventing siBCL-2 from hydrolytic degradation. Results showed CD-MOF@PDA effectively overcame the intrinsic limitations of siRNA and the agarose gel electrophoresis confirmed that CD-MOF@PDA significantly enhanced the stability of siRNA. Western blot results demonstrated that siBCL-2@CD-MOF@PDA markedly reduced the expression level of BCL-2 protein compared with free siBCL-2. In an A549 tumor model, both in vivo and ex vivo biodistribution assays demonstrated the outstanding intratumor retention capacity of siBCL-2@CD-MOF@PDA. Moreover, siBCL-2@CD-MOF@PDA achieved excellent therapeutic effects compared with other groups while maintaining favorable biocompatibility in vivo. This work may provide a potential alternative to precise gene therapy for cancer.

抗凋亡蛋白b细胞淋巴瘤2 （BCL-2）在肺癌中过度表达，是细胞凋亡逃避的关键机制。靶向BCL-2的治疗方法，如小干扰RNA (siRNA)，在肺癌治疗中具有很大的前景，但递送方面的挑战阻碍了BCL-2靶向药物的临床应用。环糊精金属有机骨架（CD-MOF）是一种易于食用的药物传递载体，具有良好的生物相容性，是基因传递的理想载体。在我们的研究中，BCL-2 siRNA （siBCL-2）被加载到cd - mof中，随后被聚多巴胺（PDA）包裹，形成siBCL-2@CD-MOF@PDA纳米平台。PDA修饰产生保护层，防止siBCL-2水解降解。结果表明CD-MOF@PDA有效地克服了siRNA固有的局限性，琼脂糖凝胶电泳证实CD-MOF@PDA显著增强了siRNA的稳定性。Western blot结果显示，siBCL-2@CD-MOF@PDA与游离siBCL-2相比，显著降低了BCL-2蛋白的表达水平。在A549肿瘤模型中，体内和离体生物分布分析均显示siBCL-2@CD-MOF@PDA具有出色的肿瘤内保留能力。此外，siBCL-2@CD-MOF@PDA与其他组相比，在保持良好的体内生物相容性的同时，取得了优异的治疗效果。这项工作可能为癌症的精确基因治疗提供潜在的替代方案。

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