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MMP2 enzyme-responsive extracellular vesicles as dual-targeted carriers to promote the phagocytosis of macrophages MMP2酶反应性细胞外囊泡作为双靶向载体促进巨噬细胞的吞噬作用。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-06 DOI: 10.1016/j.colsurfb.2024.114365
Weishen Zhong , Genpei Zhang , Kai Yue , Yongmei Song , Zitong Zhao
Combination therapy using inhibition of tumor cell escape and alteration of the tumor microenvironment offers a new strategy for cancer treatment. This study aimed to develop an extracellular vesicle (EV) carrier that regulates tumor cells and the tumor microenvironment to achieve efficient tumor immunotherapy. The ligand modified on carriers targets the immune checkpoint CD47 protein, blocking tumor cell escape. This ligand is cleaved by the MMP2 enzyme and assembles into nanofibers, extending the retention time in the tumor. The carriers target the CD206 protein, enabling efficient uptake by M2 macrophages. Carriers with a high density of ligands (anti-CD206) exhibit strong receptorligand interactions with tumor cells. Due to their high rigidity, these EVs have difficulty deforming during the transmembrane process, reducing resistance and resulting in low uptake efficiency by M2 cells. The optimal uptake efficiency by M2 macrophages is achieved when the mass ratio of ligand to EVs is 1:25. Crocin loaded in EVs facilitates the polarization of M2 macrophages into M1 cells, which can phagocytize tumor cells. This study reveals a potential strategy for using extracellular vesicles in tumor treatment.
利用抑制肿瘤细胞逃逸和改变肿瘤微环境的联合疗法为癌症治疗提供了一种新策略。这项研究旨在开发一种能调节肿瘤细胞和肿瘤微环境的细胞外囊泡(EV)载体,以实现高效的肿瘤免疫疗法。载体上修饰的配体可靶向免疫检查点 CD47 蛋白,阻止肿瘤细胞逃逸。这种配体会被 MMP2 酶裂解并组装成纳米纤维,从而延长在肿瘤中的滞留时间。这种载体以 CD206 蛋白为靶标,能被 M2 巨噬细胞有效吸收。具有高密度配体(抗 CD206)的载体能与肿瘤细胞产生强烈的受体配体相互作用。由于其刚性较高,这些 EV 在跨膜过程中难以变形,从而降低了阻力,导致 M2 细胞的摄取效率较低。当配体与 EVs 的质量比为 1:25 时,M2 巨噬细胞的摄取效率达到最佳。EVs中负载的克罗恩能促进M2巨噬细胞极化为M1细胞,从而吞噬肿瘤细胞。这项研究揭示了利用细胞外囊泡治疗肿瘤的潜在策略。
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引用次数: 0
Impact of pH-dependent dynamics of human serum proteins on dialysis membranes: Cryptographic structure assessment, synchrotron imaging of membrane-protein adsorption, and molecular docking studies 人血清蛋白的 pH 值动态对透析膜的影响:密码学结构评估、膜蛋白吸附同步辐射成像和分子对接研究。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-06 DOI: 10.1016/j.colsurfb.2024.114354
Jumanah Bahig , Hira Syeda , Ahmed Shoker , Huu Doan , Amira Abdelrasoul
Proteins are fundamental to biochemical processes and critical in hemodialysis. This study investigates the impact of pH on human serum albumin (HSA), fibrinogen (FB), and transferrin (TRF) interactions with polyarylethersulfone (PAES) hemodialysis membranes. A multi-method approach was utilized, including protein crystallography for structural insights, hydration layer analysis to explore solvation and interaction potentials, molecular docking using AutoDock 4.0 for binding affinity simulations, and in-situ X-ray synchrotron SR-μCT imaging to observe protein deposition dynamics. Molecular docking revealed that PAES demonstrated superior binding energies and interaction patterns with FB and TRF compared to cellulose triacetate (CTA), facilitated by specific hydrogen bonding within a water shell. CTA displayed weaker, hydration-sensitive interactions varying with pH. Imaging studies indicated that FB showed higher adsorption at pH 6 than at pH 7.2, predominantly in the middle membrane regions. Similarly, HSA and TRF exhibited increased adsorption at pH 6, suggesting a stronger affinity under acidic conditions. Mixed protein solutions also indicated higher adsorption at pH 6, emphasizing an increased risk of membrane fouling. These findings highlight the crucial role of pH in modulating protein-membrane interactions and enhancing the efficacy of hemodialysis. A deeper understanding of hydration environments and their effects on protein binding affinities provides valuable insights for optimizing membrane design and performance. Clinically, this research suggests that fine-tuning pH during hemodialysis could mitigate protein fouling on membranes, thereby improving procedural efficiency and potentially leading to better patient outcomes through enhanced dialysis effectiveness.
蛋白质是生化过程的基础,也是血液透析的关键。本研究探讨了 pH 值对人血清白蛋白(HSA)、纤维蛋白原(FB)和转铁蛋白(TRF)与聚芳基醚砜(PAES)血液透析膜相互作用的影响。研究采用了多种方法,包括通过蛋白质晶体学深入了解结构、通过水合层分析探索溶解和相互作用潜力、通过 AutoDock 4.0 进行分子对接模拟结合亲和力,以及通过原位 X 射线同步加速器 SR-μCT 成像观察蛋白质沉积动态。分子对接显示,与三醋酸纤维素(CTA)相比,PAES 与 FB 和 TRF 的结合能和相互作用模式更优越,这得益于水壳内的特异性氢键。CTA 显示出较弱的、对水合作用敏感的相互作用,并随 pH 值的变化而变化。成像研究表明,FB 在 pH 值为 6 时的吸附力高于 pH 值为 7.2 时的吸附力,主要吸附在膜的中间区域。同样,HSA 和 TRF 在 pH 值为 6 时也显示出更高的吸附性,这表明它们在酸性条件下具有更强的亲和力。混合蛋白溶液在 pH 值为 6 时也显示出较高的吸附性,强调了膜堵塞风险的增加。这些发现凸显了 pH 值在调节蛋白质-膜相互作用和提高血液透析疗效方面的关键作用。深入了解水合环境及其对蛋白质结合亲和力的影响,可为优化膜设计和性能提供宝贵的见解。在临床上,这项研究表明,在血液透析过程中微调pH值可以减轻蛋白质在膜上的堵塞,从而提高程序效率,并有可能通过提高透析效果来改善患者的预后。
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引用次数: 0
Strategies to enhance the hydrolytic activity of Escherichia coli BL21 penicillin G acylase based on heterologous expression and targeted mutagenesis 基于异源表达和定向诱变提高大肠杆菌 BL21 青霉素 G酰化酶水解活性的策略。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114356
Tong Ye , Zhengxu An , Mengge Song , Xiaobo Wei , Lu Liu , Xiangjun Zhang , Haojie Zhang , Huiyan Liu , Haitian Fang
Penicillin G acylase (PGA) serves as a critical biocatalyst for the hydrolysis of penicillin G, yielding 6-aminopenicillanic acid, a vital precursor for β-lactam semi-synthetic antibiotics. The catalytic efficiency of PGA, however, remains suboptimal in native Escherichia coli strains. To improve this, E. coli BL21 was engineered as a microbial cell factory via heterologous expression and site-directed mutagenesis to enhance PGA activity. The heterologous pga gene from Providencia rettgeri was integrated into E. coli BL21 (DE3) for the biosynthesis of PGA, achieving a PGA activity of 253 ± 2 U/mL after 16 hours of fermentation. The N167 site underwent mutation, producing the sites N167A and N167I. Plasmids carrying these mutations were introduced into E. coli BL21(DE3), and the enzymatic activities were recorded as 293 ± 3 U/mL for the N167A mutant and 238 ± 2 U/mL for the N167I mutant. This study not only introduces a novel approach to enhancing PGA activity but also illustrates the potential for catalytic optimization through targeted modifications of the enzyme's active site.
青霉素 G酰化酶(PGA)是水解青霉素 G 的关键生物催化剂,可产生 6-氨基青霉烷酸,这是β-内酰胺半合成抗生素的重要前体。然而,在本地大肠杆菌菌株中,PGA 的催化效率仍不理想。为了改善这一状况,我们通过异源表达和定点突变将大肠杆菌 BL21 改造成微生物细胞工厂,以提高 PGA 的活性。将来自 Providencia rettgeri 的异源 pga 基因整合到大肠杆菌 BL21 (DE3) 中,用于 PGA 的生物合成,发酵 16 小时后,PGA 活性达到 253 ± 2 U/mL。N167 位点发生突变,产生了 N167A 和 N167I 位点。将携带这些突变位点的质粒导入大肠杆菌 BL21(DE3),记录到 N167A 突变体的酶活性为 293 ± 3 U/mL,N167I 突变体的酶活性为 238 ± 2 U/mL。这项研究不仅介绍了一种提高 PGA 活性的新方法,而且还说明了通过对酶的活性位点进行靶向修饰来优化催化的潜力。
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引用次数: 0
Dexamethasone-loaded chitosan-decorated PLGA nanoparticles: A step forward in attenuating the COVID-19 cytokine storm? 地塞米松负载壳聚糖装饰PLGA纳米颗粒:在减弱 COVID-19 细胞因子风暴方面向前迈进了一步?
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114359
Mirsiane Pascoal Costa , João Octavio Carneiro Abdu , Maria Clara Machado Resende Guedes , Michelle Alvares Sarcinelli , Rodrigo Luiz Fabri , Frederico Pittella , Gilson Costa Macedo , Fernanda Maria Pinto Vilela , Helvécio Vinícius Antunes Rocha , Guilherme Diniz Tavares
This study aims to develop and characterize poly (lactic-co-glycolic acid) (PLGA) nanoparticles decorated with chitosan (CS) for the encapsulation of dexamethasone (DEX) (NP-DEX-CS), targeting improved efficacy in the treatment of severe acute respiratory syndrome (SARS) associated with COVID-19. The nanoparticles were systematically characterized for size, zeta potential (ZP), morphology, encapsulation efficiency, and in vitro drug release. Incorporation of CS resulted in significant modifications in the nanoparticles' physical properties, notably an increase in size (from 207.3 ± 6.7 nm to 264.4 ± 4.4 nm) and a shift in ZP to positive values (from −11.8 ±1.4 mV to +30.0 ± 1,6 mV). The NP-DEX-CS formulation achieved a high encapsulation efficiency (∼79 %) and a drug loading capacity of 6.53 ± 0.02 %.In addition, the in vitro release rate of DEX from NP-DEX-CS was lower compared to undecorated nanoparticles, with a reduction from approximately 64–37 % within 24 h. Microscopy analyses revealed a smoother surface on the CS-decorated nanoparticles. FTIR and XRD analyses confirmed successful chitosan coating and DEX encapsulation. The CS coating enhanced the tolerability of J774.A1 cells to the nanoparticles, particularly evident at the highest concentration (400ug/mL), resulting in a cell viability ≥70 %. Importantly, the NP-DEX-CS significantly reduced levels of nitric oxide and inflammatory cytokines (IL-1, IL-6, IL-12, and TNF-α). These findings suggest that CS-decorated PLGA nanoparticles hold promise as an effective dexamethasone delivery system for treating SARS related to COVID-19.
本研究旨在开发和表征用壳聚糖(CS)装饰的聚(乳酸-共聚-乙醇酸)(PLGA)纳米粒子,用于包封地塞米松(DEX)(NP-DEX-CS),以提高与 COVID-19 相关的严重急性呼吸系统综合征(SARS)的疗效。对纳米颗粒的尺寸、ZP、形态、封装效率和体外药物释放进行了系统表征。CS 的加入使纳米颗粒的物理性质发生了显著变化,尤其是尺寸增加(从 207.3 ± 6.7 nm 增加到 264.4 ± 4.4 nm),ZP 变为正值(从 -11.8 ± 1.4 mV 增加到 +30.0 ± 1,6 mV)。此外,NP-DEX-CS制剂的DEX体外释放率低于未装饰纳米颗粒,在24小时内降低了约64-37%。显微镜分析表明,经 CS 装饰的纳米颗粒表面更光滑。傅立叶变换红外光谱和 XRD 分析证实壳聚糖涂层和 DEX 封装成功。CS 涂层增强了 J774.A1 细胞对纳米粒子的耐受性,这在最高浓度(400ug/mL)时尤为明显,细胞存活率≥70%。重要的是,NP-DEX-CS 能显著降低一氧化氮和炎症细胞因子(IL-1、IL-6、IL-12 和 TNF-α)的水平。这些研究结果表明,CS装饰的PLGA纳米颗粒有望成为一种有效的地塞米松输送系统,用于治疗与COVID-19相关的SARS。
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引用次数: 0
Multienzyme-mimic Fe single-atom nanozymes regulate infection microenvironment for photothermal-enhanced catalytic antibacterial therapy. 多酶模拟铁单原子纳米酶调节感染微环境,用于光热增强催化抗菌疗法。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114363
Na Li, Jing Tang, Congxiao Wang, Minghui Wang, Guodong Chen, Lei Jiao, Qinglai Yang, Xiaofeng Tan

The rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O2 and H2O2 to superoxide anion free radical (•O2-) and hydroxyl radical (•OH), which possess an excellent bactericidal effect. Also, the glutathione peroxidase (GPX)-like activity of Fe SAzymes can consume glutathione in the infection microenvironment, thus facilitating ROS generation to enhance the sterilization effect. Besides, the intrinsic photothermal effect of Fe SAzymes further significantly boosts the enzyme-like activity to generate much more reactive oxygen species for efficient antibacterial therapy. Accordingly, both in vitro and in vivo results indicate that the Fe SAzymes with synergistically photothermal-catalytic performances exhibit satisfactory antibacterial effects and biocompatibility. This work provides new insights into designing highly efficient SAzymes for effective sterilization applications by an amount of ROS generation.

如何合理设计具有高效活性氧(ROS)生成能力的纳米酶来克服耐药性感染微环境仍是一项重大挑战。本文通过胶体二氧化硅诱导模板法制备了具有分层多孔纳米结构的高活性铁单原子纳米酶(Fe SAzymes)。所制备的铁单原子纳米酶具有令人满意的氧化酶(OD)样和过氧化物酶(POD)样活性,能将 O2 和 H2O2 转化为超氧阴离子自由基(-O2-)和羟自由基(-OH),具有很好的杀菌作用。同时,Fe SAzymes 的谷胱甘肽过氧化物酶(GPX)类活性可以消耗感染微环境中的谷胱甘肽,从而促进 ROS 的生成,增强杀菌效果。此外,Fe SAzymes 固有的光热效应还能进一步显著提高酶样活性,产生更多的活性氧,从而实现高效抗菌治疗。因此,体外和体内研究结果表明,具有光热催化协同作用的铁SAzymes具有令人满意的抗菌效果和生物相容性。这项工作为设计高效的 SAzymes 提供了新的见解,使其能够通过产生一定量的 ROS 有效杀菌。
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引用次数: 0
Precise photothermal treatment of bacterial infection mediated by charge-switchable nanoplatform with acylsulfonamide betaine surface. 具有酰基磺酰胺甜菜碱表面的电荷转移纳米平台介导的细菌感染精准光热疗法。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114362
Wenyuan Sun, Shumin Hu, Binzhong Lu, Yu Bao, Mengyao Guo, Yingying Yang, Qiuli Cheng, Leitao Zhang, Wenlan Wu, Junbo Li

Photothermal therapy (PTT) offers a promising approach for the treatment of drug-resistant bacterial-infected wounds, yet it requires precise targeting of thermal damage to bacteria rather than healthy tissues. Herein, ultrasmall CuS NPs modified with polyzwitterion containing acylsulfonamide betaine (PCBSA@CuS), which provides a sensitive and reversible charge conversion around pH 6.8, are used to enhance the healing of bacteria-infected wounds. In the acidic infection microenvironment, the majority of PCBSA@CuS can electrostatically adsorb onto bacterial cells through cationic exposure, resulting in direct damage and death of bacteria upon NIR irradiation. Additionally, the photothermal NPs rapidly return to a zwitterionic nature in normal physiological environments, ensuring lower affinity and avoiding thermal damage to healthy tissues during continuous PTT. Compared to inert photothermal systems such as PEG-modified CuS NPs, the NPs used in this study exhibited higher bactericidal and wound healing efficacy. Therefore, this nano-antibacterial agent with highly sensitive thermal-targeting function provides a novel photothermal strategy for efficient and biosafe treatment of infected wounds.

光热疗法(PTT)为治疗耐药细菌感染的伤口提供了一种前景广阔的方法,但它需要精确地将热损伤靶向细菌而非健康组织。在本文中,用含有酰基磺酰胺甜菜碱的聚齐聚醚(PCBSA@CuS)修饰的超小型CuS NPs被用于促进细菌感染伤口的愈合,PCBSA@CuS可在pH值为6.8时提供灵敏且可逆的电荷转换。在酸性感染微环境中,大部分 PCBSA@CuS 可通过阳离子暴露静电吸附到细菌细胞上,从而在近红外照射下直接损伤和杀死细菌。此外,光热 NPs 在正常生理环境中会迅速恢复到齐聚物性质,从而确保较低的亲和性,避免在持续 PTT 过程中对健康组织造成热损伤。与 PEG 改性 CuS NPs 等惰性光热系统相比,本研究中使用的 NPs 具有更高的杀菌和伤口愈合功效。因此,这种具有高灵敏度热靶向功能的纳米抗菌剂为高效、生物安全地治疗感染伤口提供了一种新的光热策略。
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引用次数: 0
Advances in the application of carbon dots-based fluorescent probes in disease biomarker detection. 碳点荧光探针在疾病生物标记物检测中的应用进展。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114360
Haoqi Zhang, Qingmei Zhang, Naihui Li, Guoqing Yang, Zewei Cheng, Xiujuan Du, Lingxiang Sun, Wei Wang, Bing Li

Carbon dots (CDs), as an emerging nanomaterial, have shown tremendous potential in disease biomarker detection. CDs can selectively interact with different target molecules, enabling highly sensitive and specific detection of these biomolecules. Compared to traditional detection methods, CDs sensors offer advantages such as rapid response, high detection sensitivity, and low cost. In this review, we summarize the latest advances in the application of CDs fluorescence probes for the detection of disease biomarkers, including sensing mechanisms, and their applications in the selective detection of metal ions, amino acids, enzymes, proteins, other biomolecules, as well as bacteria and viruses. We discuss the current challenges and issues associated with the practical application of CDs-based fluorescent probes. Furthermore, we propose future directions for the development of CDs. We hope that this review will provide new insights for researchers in the field of disease biomarker detection.

碳点(CD)作为一种新兴的纳米材料,在疾病生物标记物检测方面显示出巨大的潜力。碳点可以选择性地与不同的目标分子相互作用,从而实现对这些生物分子的高灵敏度和特异性检测。与传统检测方法相比,光盘传感器具有反应迅速、检测灵敏度高、成本低等优点。在这篇综述中,我们总结了应用 CDs 荧光探针检测疾病生物标志物的最新进展,包括传感机制及其在选择性检测金属离子、氨基酸、酶、蛋白质、其他生物大分子以及细菌和病毒中的应用。我们讨论了当前与基于 CD 的荧光探针的实际应用相关的挑战和问题。此外,我们还提出了 CD 的未来发展方向。我们希望这篇综述能为疾病生物标记物检测领域的研究人员提供新的见解。
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引用次数: 0
Synergistic catecholamine and coordination chemistry for enhanced bioactivity and secondary grafting activity of zirconia dental implants 儿茶酚胺和配位化学协同增强氧化锆牙科植入物的生物活性和二次移植活性。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-05 DOI: 10.1016/j.colsurfb.2024.114361
Peng Gao , Qihong Zhang , Yingyue Sun , Huan Cheng , Shuyi Wu , Yinyan Zhang , Wen Si , Haobo Sun , Ningyao Sun , Jing Yang , Kaiyong Cai , Lei Lu , Jinsong Liu
The inherent bioinertness of zirconia (ZrO2) hinders its early bone integration, presenting a significant obstacle to its widespread use in dental implant technologies. Addressing this, we developed a surface coating leveraging the synergistic effects of catecholamine and coordination chemistry inspired by the mussel byssus cuticle. This coating, named PDPA@Sr, is enriched with strontium ions and amine groups, resulting from a simple immersion of polydopamine (PD)-coated ZrO2 in an alkaline strontium chloride and poly(allylamine) (PA) solution. Compared to conventional mussel-inspired PD coatings, PDPA@Sr demonstrates enhanced aesthetic properties and mechanical stability. The continuous release of strontium ions from the coating significantly enhances osteogenesis, while the abundant surface amine groups offer notable antibacterial effects. More importantly, these amine groups also enable a variety of chemical modifications, including electrostatic adsorption, carbodiimide chemistry, Michael addition, Schiff base formation, and click chemistry, thus providing a multifaceted platform for the advanced surface modification of ZrO2 implants.
氧化锆(ZrO2)固有的生物惰性阻碍了其早期的骨整合,对其在牙科植入技术中的广泛应用构成了重大障碍。针对这一问题,我们开发了一种表面涂层,利用了儿茶酚胺和配位化学的协同作用,其灵感来自贻贝贝壳的角质层。这种被命名为 PDPA@Sr 的涂层富含锶离子和胺基团,是将涂有聚多巴胺 (PD) 的 ZrO2 简单浸泡在碱性氯化锶和聚烯胺 (PA) 溶液中产生的。与传统的贻贝启发型多巴胺涂层相比,PDPA@Sr 的美学特性和机械稳定性都有所提高。涂层中持续释放的锶离子可显著促进骨生成,而丰富的表面胺基团则具有明显的抗菌效果。更重要的是,这些胺基团还能进行多种化学修饰,包括静电吸附、碳化二亚胺化学、迈克尔加成、希夫碱形成和点击化学,从而为 ZrO2 植入物的高级表面改性提供了一个多元平台。
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引用次数: 0
Drug-induced self-assembled nanovesicles for chloroquine to sensitize MDR tumors to mitoxantrone hydrochloride. 药物诱导的氯喹自组装纳米囊,使 MDR 肿瘤对盐酸米托蒽醌敏感。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-04 DOI: 10.1016/j.colsurfb.2024.114358
Juan Wang, Xinchen Zhao, Liyan Qiu

Multidrug resistance (MDR) is an incidental trouble post-chemotherapy, necessitating innovative therapeutic strategies. This study explores the potential of chloroquine (CQ) as a sensitizer for mitoxantrone hydrochloride (MitH) in drug-resistant tumors and introduces a novel pH-responsive drug-induced self-assembly nanovesicle (DIV) based on an amphiphilic polyphosphonitrile (PPAP) for the co-delivery of MitH and CQ. PPAP cannot self-assemble into nanovesicles alone, but when a certain amount of MitH was added, the multiple non-covalent interactions between PPAP and MitH contributed to the formation of DIV, which exactly improved the co-loading content of MitH and CQ to a large extent. CQ prevents MitH efflux and autophagy to reverse MitH resistance. Given the synergy between MitH and CQ at a 1:2 mass ratio with a combination index of 0.40 in K562/ADR cells, MitH and CQ co-loaded DIV (MC-DIV) is constructed and demonstrates a sensitivity index of 7.1 on cytotoxicity compared to free MitH. Furthermore, MC-DIV achieves extended circulation time, synchronous dual-drug delivery, and improved tumor targeting following systemic administration, resulting in exceptional antitumor efficacy in K562/ADR xenograft models with a tumor inhibition rate of 83.0 %. Overall, MC-DIV provides a viable method to maximize the loading capacity of nanocarriers, and potentially serves as a promising formulation for various MitH-resistant tumors.

多药耐药性(MDR)是化疗后的一个附带问题,需要创新的治疗策略。本研究探讨了氯喹(CQ)作为盐酸米托蒽醌(MitH)的增敏剂在耐药肿瘤中的潜力,并介绍了一种基于两亲性聚磷腈(PPAP)的新型pH响应药物诱导自组装纳米微粒(DIV),用于联合递送MitH和CQ。PPAP不能单独自组装成纳米微粒,但当加入一定量的MitH后,PPAP与MitH之间的多种非共价相互作用促成了DIV的形成,从而在很大程度上恰好提高了MitH和CQ的共负载含量。CQ可防止MitH外流和自噬,从而逆转MitH抗性。鉴于 MitH 和 CQ 在 K562/ADR 细胞中以 1:2 的质量比发挥协同作用,其组合指数为 0.40,因此构建了 MitH 和 CQ 共载 DIV(MC-DIV),与游离 MitH 相比,其细胞毒性敏感性指数为 7.1。此外,MC-DIV 还能延长血液循环时间,实现同步双药递送,并在全身给药后提高肿瘤靶向性,从而在 K562/ADR 异种移植模型中发挥卓越的抗肿瘤功效,肿瘤抑制率高达 83.0%。总之,MC-DIV 为最大限度地提高纳米载体的负载能力提供了一种可行的方法,并有可能成为治疗各种 MitH 抗性肿瘤的一种有前途的制剂。
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引用次数: 0
Artemisinin and salinomycin co-loaded nanozymes to boost cascade ROS accumulation for augmented tumor ferroptosis. 青蒿素和盐霉素共载纳米酶促进级联 ROS 积累,从而增强肿瘤铁变态反应。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2024-11-02 DOI: 10.1016/j.colsurfb.2024.114352
MengXiao Liu, Ying Lu, JunSheng Zhao, YanZhao Yin, Jin Cao, Lin Wu, Song Shen

Ferroptosis, which depends on iron ions to generate reactive oxygen species (ROS), has been proved to be an effective strategy for cancer therapy. However, cells will initiate different programs, including reducing iron uptake and storing excess iron in ferritin, to lower the intracellular iron concentration. In this work, we reported a simple, one-pot method to synthesize bovine serum albumin stabilized MnFe2O4 nanoparticles (MnFe2O4@BSA NPs) for ferroptosis therapy of cancer. Artemisinin (ART) and salinomycin (Sali), which could induce the degradation of ferritin and enhance the uptake by increasing binding protein IRP2 and transferrin receptor, were loaded onto the MnFe2O4@BSA NPs to strengthen the killing effect. The prepared MnFe2O4@BSA-ART/Sali (MnFe2O4/ART/Sali) NPs could significantly increase the cellular iron concertation, enhancing the ROS generation in cells. After intravenous injection, the MnFe2O4/ART/Sali NPs showed superior anti-tumor effects, with a tumor inhibition rate of 67.65 %. Hence, the hybrid nanocomposite indicated the combined effect of MnFe2O4, ART, and Sali, providing a platform to enhance ferroptosis therapy of cancer.

铁变态反应依赖于铁离子产生活性氧(ROS),已被证明是一种有效的癌症治疗策略。然而,细胞会启动不同的程序,包括减少铁的吸收和将多余的铁储存在铁蛋白中,以降低细胞内的铁浓度。在这项工作中,我们报道了一种简单的一锅法合成牛血清白蛋白稳定的 MnFe2O4 纳米粒子(MnFe2O4@BSA NPs),用于癌症的铁氧化疗法。青蒿素(ART)和盐霉素(Sali)可诱导铁蛋白降解,并通过增加结合蛋白 IRP2 和转铁蛋白受体来提高铁蛋白的摄取量。制备的MnFe2O4@BSA-ART/Sali(MnFe2O4/ART/Sali)NPs能显著增加细胞中铁的协同作用,增强细胞中ROS的生成。经静脉注射后,MnFe2O4/ART/Sali NPs显示出卓越的抗肿瘤效果,肿瘤抑制率达67.65%。因此,该混合纳米复合材料显示了 MnFe2O4、ART 和 Sali 的联合作用,为加强癌症的铁氧化疗法提供了一个平台。
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Colloids and Surfaces B: Biointerfaces
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