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Computational exploration of the self-aggregation mechanisms of phenol-soluble modulins β1 and β2 in Staphylococcus aureus biofilms 金黄色葡萄球菌生物膜中酚溶性调节素β1和β2自聚集机制的计算探索。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-05 DOI: 10.1016/j.colsurfb.2025.114498
Huan Xu , Xiaohan Zhang , Zhongyue Lv , Fengjuan Huang , Yu Zou , Chuang Wang , Feng Ding , Yunxiang Sun
The formation of functional bacterial amyloids by phenol-soluble modulins (PSMs) in Staphylococcus aureus is a critical component of biofilm-associated infections, providing robust protective barriers against antimicrobial agents and immune defenses. Clarifying the molecular mechanisms of PSM self-assembly within the biofilm matrix is essential for developing strategies to disrupt biofilm integrity and combat biofilm-related infections. In this study, we analyzed the self-assembly dynamics of PSM-β1 and PSM-β2 by examining their folding and dimerization through long-timescale atomistic discrete molecular dynamics simulations. Our findings revealed that both peptides primarily adopt helical structures as monomers but shift to β-sheets upon dimerization. Monomeric state, PSM-β1 exhibited frequent transitions between helical and β-sheet forms, while PSM-β2 largely retained a helical structure. Upon dimerization, both peptides showed pronounced β-sheet formation around conserved C-terminal residues 21–44. Residues 21–33, largely unstructured as monomers, demonstrated strong tendencies for β-sheet formation and intermolecular interactions, underscoring their central role in the self-assembly of both peptides. Additionally, the PSM-β1 N-terminus formed β-sheets only when interacting with the C-terminus, whereas the PSM-β2 N-terminus remained helical and uninvolved in β-sheet formation. These distinct aggregation behaviors likely contribute to biofilm dynamics, with C-terminal regions facilitating biofilm formation and N-terminal regions influencing stability. Targeting residues 21–33 in PSM-β1 and PSM-β2 offers a promising therapeutic approach for disrupting biofilm integrity. This study advances our understanding of PSM-β1 and PSM-β2 self-assembly and presents new targets for drug design against biofilm-associated diseases.
金黄色葡萄球菌中酚溶性调节素(psm)形成功能性细菌淀粉样蛋白是生物膜相关感染的关键组成部分,为抗微生物药物和免疫防御提供了强大的保护屏障。阐明PSM在生物膜基质内自组装的分子机制对于制定破坏生物膜完整性和对抗生物膜相关感染的策略至关重要。在这项研究中,我们通过长时间尺度的原子离散分子动力学模拟,研究了PSM-β1和PSM-β2的折叠和二聚化,分析了它们的自组装动力学。我们的研究结果表明,这两种肽主要采用螺旋结构作为单体,但在二聚化时转变为β-片。在单体状态下,PSM-β1表现出螺旋和β片之间的频繁转变,而PSM-β2则基本保持螺旋结构。二聚化后,两种多肽在保守的c端残基21-44周围显示明显的β-薄片形成。残基21-33大部分是非结构化单体,表现出β-薄片形成和分子间相互作用的强烈倾向,强调了它们在两种肽的自组装中的核心作用。此外,PSM-β1 n -端仅在与c -端相互作用时形成β-片,而PSM-β2 n -端则保持螺旋状,不参与β-片的形成。这些不同的聚集行为可能有助于生物膜动力学,c端区域促进生物膜的形成,n端区域影响稳定性。靶向PSM-β1和PSM-β2残基21-33为破坏生物膜完整性提供了一种有前景的治疗方法。该研究促进了我们对PSM-β1和PSM-β2自组装的认识,并为生物膜相关疾病的药物设计提供了新的靶点。
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引用次数: 0
Coaxial bioprinting of a three-layer vascular structure exhibiting blood-brain barrier function for neuroprotective drug screening 具有血脑屏障功能的三层血管结构的同轴生物打印用于神经保护药物筛选。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-03 DOI: 10.1016/j.colsurfb.2025.114494
Zhichao Wang , Chuanzhen Huang , Zhenyu Shi , Hanlian Liu , Xu Han , Zhuang Chen , Shuying Li , Zhen Wang , Jun Huang
The in vitro blood-brain barrier (BBB) structures can offer advantages for studying cerebrovascular functions and developing neuroprotective drugs. However, currently developed BBB models are overly simplistic and inadequate for replicating the complex three-dimensional architecture of the in vivo BBB. In this study, a method is introduced for fabricating a three-layer vascular structure exhibiting BBB function using a coaxial extrusion bioprinting technique with a two-layer nozzle. Photocurable materials were incorporated into the inner layer of the coaxial nozzle, and photoinitiators from the outer layer diffused into the inner layer. As a result, only the materials in the inner layer at the interface between the inner and outer layers underwent crosslinking upon UV exposure. After removing the uncrosslinked materials, a two-layer vascular structure can be formed. Subsequently, a three-layer structure was established after seeding endothelial cells. The perfusion experiments demonstrated that the vascular structure facilitated the continuous flow of culture medium, thereby providing nutrients and oxygen to the surrounding neural tissue. The drug screening analysis indicated that this vascular structure could possess barrier function, allowing the passage of small molecular drugs while effectively blocking macromolecular drugs. Overall, these results suggest that the three-layer vascular structure exhibits excellent perfusion capacity and barrier function, making it a promising candidate for neuroprotective drug screening.
体外血脑屏障(BBB)结构为研究脑血管功能和开发神经保护药物提供了有利条件。然而,目前开发的血脑屏障模型过于简单,不足以复制体内血脑屏障复杂的三维结构。在这项研究中,介绍了一种利用同轴挤压生物打印技术和两层喷嘴制造具有血脑屏障功能的三层血管结构的方法。将光固化材料掺入同轴喷嘴的内层,光引发剂从外层扩散到内层。因此,在紫外线照射下,只有内层和外层之间的界面处的材料发生交联。去除非交联材料后,可形成两层维管结构。随后,内皮细胞植入后形成三层结构。灌注实验表明,血管结构促进了培养基的连续流动,从而为周围神经组织提供营养和氧气。药物筛选分析表明,该血管结构具有屏障功能,允许小分子药物通过,同时有效阻断大分子药物。综上所述,三层血管结构具有良好的灌注能力和屏障功能,是神经保护药物筛选的理想候选者。
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引用次数: 0
PAMAM/miR-144 nanocarrier system inhibits the migration of gastric cancer by targeting mTOR signal transduction pathway PAMAM/miR-144纳米载体系统通过靶向mTOR信号转导通路抑制胃癌的迁移。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-03 DOI: 10.1016/j.colsurfb.2024.114492
Yayun Qian , Dongxu Zhu , Qiong Xu , Yujie Wang , Xiwen Chen , Weiwei Hua , Juqun Xi , Feng Lu
Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.
外源性microRNA-144 (miR-144)具有抑制上皮-间质转化(epithelial-mesenchymal transition, EMT)的生物活性,被认为是治疗胃癌的潜在生物药物。然而,具体的分子机制尚未完全揭示。此外,它们易被血液中的RNA酶降解,限制了它们的生物利用度。本文制备了聚酰胺胺(PAMAM)包裹的miR-144 (PAMAM/miR-144)作为纳米载体体系来保护miR-144免受核酸酶降解。PAMAM/miR-144纳米载体系统通过将miR-144转移到人胃癌HGC-27细胞中,实现对胃癌迁移的最佳抗肿瘤活性,并降低mTOR蛋白的表达。同时,PAMAM/miR-144纳米载体系统通过靶向mTOR信号通路,显著降低HGC-27细胞的EMT,显著抑制裸鼠皮下胃癌异种移植物的生长。PAMAM/miR-144纳米载体体系有效提高了miR-144的生物利用度,为抗癌治疗提供了一种很有前景的联合方式。
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引用次数: 0
Integration of EMAP-II-targeted anti-angiogenesis and photodynamic therapy using zinc phthalocyanine nanosystem for enhanced cancer treatment 结合emap - ii靶向抗血管生成和光动力治疗,使用锌酞菁纳米系统增强癌症治疗。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-03 DOI: 10.1016/j.colsurfb.2024.114493
Liyun Chen , Linlin Li , Hailong Zhao , Hao Li , Jiahui Li , Chao Li , Yang Zhou , Luxuan Yang , Jun Liang , Honglian Zhang , Juan Li , Peng Xu , Cai Yuan , Zhenhua Liu , Mingdong Huang , Longguang Jiang
Angiogenesis provides essential nutrients and oxygen to tumors during tumorigenesis, facilitating invasion and metastasis. Consequently, inhibiting tumor angiogenesis is an established strategy in anti-cancer therapy. In this study, we engineered a dual-function nanosystem with both antiangiogenic and photodynamic properties. We transformed the hydrophobic photosensitizer zinc phthalocyanine (PS) into a hydrophilic form via protein renaturation, resulting in a novel photosensitizer: Monocyte-Activating Polypeptide-II (EMAP-II:PS@NPs). Characterization through dynamic light scattering (DLS) and UV–vis spectroscopy showed that these nanoparticles exhibited uniform size and stability, and enhanced solubility. We further demonstrated that EMAP-II:PS@NPs effectively target tumor vascular endothelia causing intracellular photodynamic cytotoxicity. Notably, EMAP-II:PS@NPs achieved effective ablation of solid tumors at significantly reduced dosages of drugs compared to conventional therapies, due to their potent apoptotic effects on light-exposed cells. This study highlights the potential of combining anti-angiogenic activity with phototherapy, paving the way for innovative cancer treatment strategies.
血管生成在肿瘤发生过程中为肿瘤提供必需的营养和氧气,促进肿瘤的侵袭和转移。因此,抑制肿瘤血管生成是抗癌治疗的既定策略。在这项研究中,我们设计了一种具有抗血管生成和光动力特性的双功能纳米系统。我们将疏水性光敏剂酞菁锌(PS)通过蛋白质复性转化为亲水性形式,得到了一种新型光敏剂:单核细胞激活多肽ii (EMAP-II:PS@NPs)。动态光散射(DLS)和紫外可见光谱表征表明,这些纳米颗粒具有均匀的尺寸和稳定性,并且具有增强的溶解度。我们进一步证明EMAP-II:PS@NPs有效靶向肿瘤血管内皮,引起细胞内光动力细胞毒性。值得注意的是,与传统疗法相比,EMAP-II:PS@NPs在显著减少的药物剂量下实现了实体瘤的有效消融,这是由于它们对暴露于光下的细胞具有强大的凋亡作用。这项研究强调了将抗血管生成活性与光疗相结合的潜力,为创新的癌症治疗策略铺平了道路。
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引用次数: 0
Self-assembled water soluble and bone-targeting phosphorylated quercetin ameliorates postmenopausal osteoporosis in ovariectomy mice 自组装水溶性和骨靶向磷酸化槲皮素改善卵巢切除术小鼠绝经后骨质疏松症。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-03 DOI: 10.1016/j.colsurfb.2025.114495
Peng Luo , Yanlong Zhong , Xiaowei Yang , Qi Lai , Shaorong Huang , Xiaoyong Zhang , Bin Zhang , Yen Wei
Natural compounds have shown promising application prospects in preventing or treating various diseases, including osteoporosis on account of their abundant sources, low price, multi-targeting and multiple biological effects. As a bioactive natural product, quercetin (Que) has previously demonstrated to ameliorate osteoporosis (OP), however, its poor bioavailability resulting from low water solubility, poor stability and lack of bone-targeting largely restricted its efficacy and clinical applications. Inspired by the bone-targeting capability of phosphate compounds, we reported a one-step procedure for synthesis of phosphorylated Que (p-Que) by direct phosphorylating phenol groups of Que for the first time. The phosphate groups on p-Que could not only improve the water dispersibility of Que, but also endow p-Que desirable bioavailability and bone-targeting feature. The results from biological assays suggested that p-Que could inhibit osteoclastogenesis and bone resorption and alleviate trabeculae loss in osteoporotic mice. In conclusion, this work demonstrated that phosphorylation strategy can effectively solve low water solubility, lack of bone-targeting capability and poor bioavailability of natural compounds, providing a novel and efficient approach for development of OP nanomedicines.
天然化合物以其来源丰富、价格低廉、多靶点和多种生物效应在预防或治疗包括骨质疏松症在内的多种疾病方面显示出广阔的应用前景。槲皮素(quercetin, Que)作为一种具有生物活性的天然产物,曾被证明具有改善骨质疏松症(osteoporosis, OP)的作用,但由于其水溶性低、稳定性差、缺乏骨靶向性等原因,其生物利用度较差,在很大程度上限制了其疗效和临床应用。受磷酸盐化合物骨靶向能力的启发,我们首次报道了通过直接磷酸化Que的酚基一步合成磷酸化Que (p-Que)的方法。p-Que上的磷酸基团不仅提高了Que的水分散性,而且赋予了p-Que良好的生物利用度和骨靶向特性。生物实验结果表明,p-Que能抑制骨质疏松小鼠破骨细胞生成和骨吸收,减轻骨质疏松小鼠小梁丢失。综上所述,本研究表明磷酸化策略可以有效解决天然化合物水溶性低、骨靶向能力不足和生物利用度差的问题,为OP纳米药物的开发提供了一种新的高效途径。
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引用次数: 0
Enhanced MRSA-infected wound healing using tannic acid cross-linked carboxymethyl chitosan/polyglutamic acid hydrogel for carbazole Delivery 使用鞣酸交联羧甲基壳聚糖/聚谷氨酸水凝胶进行卡巴唑给药,促进 MRSA 感染伤口的愈合。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-02 DOI: 10.1016/j.colsurfb.2024.114490
Soureh Sadat Mirzamani , Mohammad Reza Farahpour , Zohreh Ghazi Tabatabaei
The rampant use of commercial antibiotics not only increases drug resistance but also causes a significant threat to human health. This study assessed the wound healing efficacy of hydrogels crafted from carboxymethyl chitosan (Cmc), polyglutamic acid (γ-PGA), tannic acid (TA), and carbazole (Car), with the aim of expediting the wound healing process. Hydrogels were formulated using Cmc/γ-PGA, Cmc/γ-PGA/TA, and Cmc/γ-PGA/TA/Car, followed by a thorough evaluation of their physicochemical attributes. Additionally, assessments encompassed cytotoxicity, antibacterial efficacy, wound contraction rates, histopathological parameters, immunofluorescent staining of CD31, CD86, and COL1A, along with the determination of serum concentrations of IL-1β, IL-6, and IL-10. The physicochemical analyses validated the successful synthesis of the hydrogels, which exhibited both safety and potent antibacterial properties. Topical application of Cmc/γ-PGA/TA/Car hydrogels notably accelerated wound contraction, as evidenced by heightened expression of CD31 and COL1A, alongside reduced serum concentrations of IL-1β and IL-6. In essence, the Cmc/γ-PGA/TA/Car hydrogel demonstrated a dual effect of mitigating inflammation and modulating the proliferative phase, that shows their abilities for application in the wound healing process.
商业抗生素的猖獗使用不仅增加了耐药性,而且对人类健康造成了重大威胁。本研究评估了羧甲基壳聚糖(Cmc)、聚谷氨酸(γ-PGA)、单宁酸(TA)和咔唑(Car)制备的水凝胶的伤口愈合效果,旨在加速伤口愈合过程。采用Cmc/γ-PGA、Cmc/γ-PGA/TA和Cmc/γ-PGA/TA/Car配制水凝胶,并对其理化性质进行了全面评价。此外,评估包括细胞毒性、抗菌效果、伤口收缩率、组织病理学参数、CD31、CD86和COL1A的免疫荧光染色,以及血清IL-1β、IL-6和IL-10浓度的测定。物理化学分析证实了水凝胶的成功合成,该水凝胶具有安全性和强抗菌性。局部应用Cmc/γ-PGA/TA/Car水凝胶可显著加速创面收缩,CD31和COL1A表达升高,血清IL-1β和IL-6浓度降低。从本质上说,Cmc/γ-PGA/TA/Car水凝胶具有减轻炎症和调节增殖期的双重作用,显示了它们在伤口愈合过程中的应用能力。
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引用次数: 0
Albendazole nanosuspension coated granules for the rapid localized release and treatment of colorectal cancer. 用于快速局部释放和治疗结直肠癌的阿苯达唑纳米悬浮包衣颗粒。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-01 Epub Date: 2024-10-15 DOI: 10.1016/j.colsurfb.2024.114320
Yi Guo, Henis J Patel, Akanksha S Patel, Emilio Squillante, Ketan Patel

Albendazole (ABZ), an anthelmintic drug, has been repurposed to treat various types of cancers. However, poor solubility of ABZ, resulting in low bioavailability, limits its application. Nanosuspension is a versatile method for enhancing the dissolution of hydrophobic molecules, but a successful drying has been the biggest challenge in the field. The objective of this research is to formulate and optimize ABZ nanosuspension (NS) coated granules for rapid delivery of ABZ for the treatment of colorectal cancer. ABZ NS was prepared by dual centrifugation method using Kollidon® VA64 and sodium lauryl sulphate (SLS) as stabilizers. The processing method was optimized to obtain a stable nanosuspension with particle size < 300 nm. The optimized ABZ NS was coated on microcrystalline cellulose (MCC) to form the nano-coated granules (NCG) and filled in EUDRACAP® for colon targeted delivery. The ABZ NS and NCG achieved ∼ 60 % and ∼55 % drug release, respectively, in presence of bile salt at colonic pH. Half-maximal inhibitory concentration (IC50) of ABZ NS was found to be 1.18 ± 0.081 µM and 3.59 ± 0.080 µM in two colorectal cancer cell lines: HCT 116 and HT-29, respectively. In addition, In vitro 3D tumor assay revealed that ABZ NS has superior tumor growth inhibition activity compared to the control and pure ABZ. The preparation of ABZ NCG in EUDRACAP® could be a promising approach to achieve colon targeted delivery and to repurpose ABZ for the treatment of colorectal cancer.

阿苯达唑(ABZ)是一种驱虫药,已被重新用于治疗各种癌症。然而,阿苯达唑的溶解性差,导致生物利用率低,限制了其应用。纳米悬浮是一种提高疏水性分子溶解度的多功能方法,但成功干燥一直是该领域的最大挑战。本研究的目的是配制和优化 ABZ 纳米悬浮剂(NS)包衣颗粒,用于快速递送 ABZ 治疗结直肠癌。采用 Kollidon® VA64 和十二烷基硫酸钠(SLS)作为稳定剂,通过双离心法制备 ABZ NS。对加工方法进行了优化,以获得粒径小于 300 nm 的稳定纳米悬浮液。将优化后的 ABZ NS 涂覆在微晶纤维素(MCC)上形成纳米包衣颗粒(NCG),并填充到 EUDRACAP® 中进行结肠靶向给药。在胆盐存在的结肠pH条件下,ABZ NS和NCG的药物释放率分别为60%和55%。在两种结直肠癌细胞系中,ABZ NS 的半最大抑制浓度(IC50)分别为 1.18 ± 0.081 µM 和 3.59 ± 0.080 µM:分别为 1.18 ± 0.081 µM 和 3.59 ± 0.080 µM。此外,体外三维肿瘤试验显示,与对照组和纯 ABZ 相比,ABZ NS 具有更强的肿瘤生长抑制活性。在EUDRACAP®中制备ABZ NCG可能是实现结肠靶向给药和将ABZ重新用于治疗结直肠癌的一种很有前景的方法。
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引用次数: 0
Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity. 可编程释放药物的氧化还原反应降解抗菌剂,增强抗菌活性。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-01 Epub Date: 2024-10-09 DOI: 10.1016/j.colsurfb.2024.114308
Yue Zhang, Xuehan Yang, Yawei Zhao, Fangman Chen, Tongfei Shi, Ziping Wu, Xuenian Chen, Ming Zhang, Li Chen

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.

全球抗生素耐药性危机促使人们必须开发更有效的给药系统来治疗细菌感染。开发具有高生物相容性和靶向递送抗菌药物的系统仍是一项长期挑战。为了在感染部位可编程地释放高效抗菌素以增强抗菌活性,我们在本文中制备了具有高载药量的二硒化桥键介孔有机硅纳米颗粒-银纳米颗粒(Ag NPs),用于在一个给药系统(Ag-MON@TOB (Se))中联合给药妥布霉素(TOB)。制备出的 Ag-MON@TOB (Se) 在生理条件下具有高稳定性,因而具有良好的生物相容性。值得注意的是,这种Ag-MON@TOB(Se)具有可编程的结构失稳性,可根据细菌感染微环境中的氧化刺激触发药物的连续释放。与纳米载体框架内氧化稳定的二硫键分子(Ag-MON@TOB (S))不同,Ag-MON@TOB (Se)的可编程药物释放行为增强了体外和体内的抗菌治疗效果。这项工作代表了通过利用反应灵敏的可降解载体来提高细菌感染治疗效果的可编程药物释放策略的前景。
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引用次数: 0
Multifunctional mesoporous nanoselenium delivery of metformin breaks the vicious cycle of neuroinflammation and ROS, promotes microglia regulation and alleviates Alzheimer's disease. 多功能介孔纳米硒递送二甲双胍打破了神经炎症和 ROS 的恶性循环,促进了小胶质细胞的调节,缓解了阿尔茨海默病。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/j.colsurfb.2024.114300
Xian Guo, Borui Zhang, Yutong Chen, Zhi Jia, Xiaoyu Yuan, Li Zhang, Jie Liu, Yanan Liu

Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aβ protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aβ deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.

基于单一分子靶点的临床试验不断失败,Aβ蛋白聚集和神经炎症的不良影响亟待解决,阿尔茨海默病的治疗也是如此。本文通过设计一种具有高酶样活性的纳米级花介孔硒转运载体(Met@MSe@Tf),载入二甲双胍(Met),并修饰转铁蛋白(Tf)与转铁蛋白受体结合,促进受体介导的跨BBB转运。在AD病变环境中,与酸性环境反应解离,促进二甲双胍通过纳米花释放,在脑部病变部位达到治疗效果。二甲双胍是糖尿病代谢中的主要抗糖尿病药物,已被发现是神经退行性疾病的一个有希望的新治疗靶点。进一步的研究表明,二甲双胍药物从设计合成的转运纳米颗粒中释放,表现出较高的内在活性和降解相关底物的能力,尤其是降解大脑皮层和海马中的Aβ沉积,增加小胶质细胞的吞噬能力,从而同时缓解神经炎症。总之,体内实验证明,Met@MSe@Tf能显著增加AD小鼠海马中NeuN阳性神经元的数量,促进大脑神经血管正常化,改善AD转基因小鼠的认知功能障碍。因此,它为构建治疗阿尔茨海默病的高度模块化精准给药平台提供了临床前概念验证。
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引用次数: 0
Multifunctional NIR-II nanoplatform for disrupting biofilm and promoting infected wound healing. 用于破坏生物膜和促进感染伤口愈合的多功能 NIR-II 纳米平台。
IF 5.4 2区 医学 Q1 BIOPHYSICS Pub Date : 2025-01-01 Epub Date: 2024-10-23 DOI: 10.1016/j.colsurfb.2024.114330
Jinqiang Wu, Xiaolei Huo, Jinjia Liu, Fanqiang Bu, Pengfei Zhang

Healing wounds presents a significant challenge due to bacterial biofilm infections and the inherent drug resistance of these biofilms. This report introduces a multifunctional nanoplatform (NPs) designed to combat wound biofilm infections using NIR-II photothermal therapy. The NPs are self-assembled from amphiphilic polymers (AP) to encapsulate photothermal polymers (PT) through classic electrostatic interactions. Importantly, these NPs are electrically neutral, which enhances their ability to penetrate biofilms effectively. Once inside the biofilm, the NPs achieve complete thermal ablation of the biofilm under NIR-II laser irradiation. Additionally, when exposed to laser and the GSH microenvironment, the NPs exhibit strong photothermal effects and self-degradation capabilities. In vitro tests confirm that the NPs have excellent antibacterial and anti-biofilm properties against methicillin-resistant Staphylococcus aureus (MRSA). In vivo studies demonstrate that the NPs can efficiently clear wound biofilm infections and promote wound healing. Notably, the NPs show superior photothermal effects under NIR-II laser irradiation compared to NIR-I lasers. In summary, the developed NPs serve as an integrated diagnostic and therapeutic nano-antimicrobial agent, offering promising applications for biofilm wound infections and wound healing.

由于细菌生物膜感染以及这些生物膜固有的抗药性,伤口愈合是一项重大挑战。本报告介绍了一种多功能纳米平台(NPs),旨在利用近红外-II 光热疗法对抗伤口生物膜感染。NPs 由两亲聚合物 (AP) 自组装而成,通过典型的静电相互作用封装光热聚合物 (PT)。重要的是,这些 NPs 呈电中性,这增强了它们有效穿透生物膜的能力。一旦进入生物膜,NPs 就能在近红外-II 激光照射下实现对生物膜的完全热消融。此外,在激光和 GSH 微环境的作用下,NPs 表现出很强的光热效应和自我降解能力。体外试验证实,这种 NPs 对耐甲氧西林金黄色葡萄球菌(MRSA)具有出色的抗菌和抗生物膜特性。体内研究表明,NPs 能有效清除伤口生物膜感染,促进伤口愈合。值得注意的是,在近红外-II 激光照射下,NPs 比近红外-I 激光显示出更优越的光热效应。总之,所开发的 NPs 可作为一种集诊断和治疗为一体的纳米抗菌剂,在生物膜伤口感染和伤口愈合方面具有广阔的应用前景。
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Colloids and Surfaces B: Biointerfaces
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