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Isolation-free measurement of single urinary extracellular vesicles by imaging flow cytometry. 成像流式细胞术对单个尿细胞外囊泡的无隔离测定。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-12-01 DOI: 10.2139/ssrn.4240649
Liang Wu, W. Woud, C. Baan, D. Hesselink, E. van der Pol, G. Jenster, K. Boer
Urinary extracellular vesicles (uEVs) are promising biomarkers for various diseases. However, many tools measuring uEVs rely on time-consuming uEV isolation methods, which could induce sample bias. This study demonstrates the detection of single uEVs without isolation using imaging flow cytometry (IFCM). Unstained urine samples contained auto-fluorescent (A-F) particles when characterized with IFCM. Centrifugation successfully removed A-F particles from the unprocessed urine. Based on the disappearance of A-F particles, a gate was defined to distinguish uEVs from A-F particles. The final readouts of IFCM were verified as single EVs based on detergent treatment and serial dilutions. When developing this protocol to measure urine samples with abnormally high protein levels, 25 mg/mL dithiothreitol (DTT) showed improved uEV recovery over 200 mg/mL DTT. This study provides an isolation-free protocol using IFCM to quantify and phenotype single uEVs, eliminating the hindrance and influence of A-F particles, protein aggregates, and coincidence events.
尿细胞外囊泡(uEVs)是一种很有前景的生物标志物。然而,许多测量uEV的工具依赖于耗时的uEV分离方法,这可能会导致样本偏差。本研究展示了成像流式细胞术(IFCM)在不分离的情况下检测单个uev。未染色的尿液样本含有自动荧光(A-F)颗粒,用IFCM进行表征。离心成功地从未处理的尿液中去除A-F颗粒。基于a - f粒子的消失,定义了一个栅极来区分uev和a - f粒子。根据洗涤剂处理和连续稀释,IFCM的最终读数被验证为单个ev。在制定该方案以测量异常高蛋白水平的尿液样本时,25 mg/mL二硫苏糖醇(DTT)比200 mg/mL DTT显示出更高的uEV回收率。本研究提供了一种无分离的方案,使用IFCM对单个uev进行量化和表型分析,消除了A-F颗粒、蛋白质聚集体和巧合事件的阻碍和影响。
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引用次数: 3
Muscle cytotoxicity and immuno-reactivity analysis of the porous carbon nanospheres fabricated by high temperature calcination. 高温煅烧制备多孔碳纳米球的肌肉细胞毒性和免疫反应性分析。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-11-01 DOI: 10.2139/ssrn.4182790
Jingwen Huang, Xiaoting Jian, Mengmeng Xu, Han Wang, Zhaohong Liao, Hai-ying Lan, Linge Wang, Jijie Hu, Qianqian Yu, Hua Liao
Carbon-based nanomaterials have a high specific surface area, biocompatibility, and controlled mesopore structures. These characteristics make carbon nanospheres excellent carriers for drugs, biological dyes, photosensitizers, etc. Nevertheless, little is known about the impact of topological features on the surface of carbon nanomaterials on their in vivo immunoreactivity. In this study, we fabricated mesoporous carbon nanoparticles (MCNs) and solvent-processable carbon vesicles (CVs) by high-temperature calcination. The hematoxylin and eosin (H&E) staining suggested CVs' relatively poor dispersion capacity compared to MCNs and carbon precursors (CPs), leading to more severe muscle inflammation and necrosis. Immunostaining and Fluorescence Activated Cell Sorter (FACS) analysis further showed that both MCNs and CVs triggered a transient immune response in transplanted muscle and muscle-draining lymph nodes, but did not alter muscle resistance to exogenous viruses. In conclusion, this study provides insights into how carbon nanoparticles modulate the activation of immune responses in vivo.
碳基纳米材料具有高比表面积、生物相容性和可控的介孔结构。这些特性使碳纳米球成为药物、生物染料、光敏剂等的优良载体。然而,对于碳纳米材料表面的拓扑特征对其体内免疫反应性的影响知之甚少。在这项研究中,我们通过高温煅烧制备了介孔碳纳米颗粒(MCNs)和溶剂可加工碳囊泡(CVs)。苏木精和伊红(H&E)染色表明,与mcn和碳前体(CPs)相比,CVs的分散能力相对较差,导致更严重的肌肉炎症和坏死。免疫染色和荧光活化细胞分选(FACS)分析进一步表明,mcn和CVs在移植肌肉和肌肉引流淋巴结中触发了短暂的免疫反应,但没有改变肌肉对外源性病毒的抵抗力。总之,本研究提供了碳纳米颗粒如何调节体内免疫反应激活的见解。
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引用次数: 0
A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting. 利用外膜囊泡的组合化疗免疫疗法,通过 RGD 靶向增强癌症治疗。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-10-15 DOI: 10.1016/j.nano.2022.102610
Shuping Li, Xiaodong Gao

Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.

癌症疗法因药物渗透性差而受到限制,从而阻碍了对肿瘤的有效治疗。本研究通过将诱导免疫反应的细菌外膜囊泡纳米载体和多柔比星(DOX)装入天然免疫平台 OMV 进行孵育,克服了这一难题。通过在 OMVs 表面使用靶向肽 6-Mal- Arg-Gly-Asp (RGD),增加与细胞表面整合素 αvβ3 的结合,从而提高药物在肿瘤部位的蓄积。OMV 通过减少 TAM 和 Treg、增加 CD8+ T 和 M1 以及促进 DC 成熟来逆转免疫抑制性肿瘤微环境 (TME),从而刺激免疫反应。DOX 和 OMVs 的结合弥补了单一疗法(如化疗和免疫疗法)的不足,扩大了癌症治疗的疗效,同时有助于新型纳米载体的选择和有效治疗方案的开发。
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引用次数: 0
A combinational chemo-immune therapy using outer membrane vesicles for enhanced cancer therapy by RGD targeting. 一种利用外膜囊泡增强肿瘤RGD靶向治疗的化学免疫联合疗法。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-10-01 DOI: 10.2139/ssrn.4156334
Shuping Li, Xiaodong Gao
Cancer therapies are limited by poor drug penetration that impedes effective tumor treatment. This was overcome in the present study by loading the immune reaction inducing nanocarriers of the bacterial outer membrane vesicles (OMVs) and doxorubicin (DOX) into the natural immunity platform OMV via incubation. Drug accumulation at the tumor site was improved by using the targeting peptide 6-Mal- Arg-Gly-Asp (RGD) on the surface of OMVs to increase internalization via binding to cell surface integrin αvβ3. OMVs stimulate immune responses by reversing the immune-suppressive tumor microenvironment (TME) via decreasing TAM and Treg, increasing CD8+ T and M1, and promoting DC maturation. The combination of DOX and OMVs compensates for the shortcomings of monotherapy (e.g., chemotherapy and immunotherapy) and amplifies the therapeutic efficacy of cancer treatment, while aiding selection of novel nanocarriers and development of effective therapeutic regimens.
由于药物渗透性差,阻碍了肿瘤的有效治疗,癌症治疗受到了限制。本研究通过将诱导免疫反应的细菌外膜囊泡(OMVs)和阿霉素(DOX)纳米载体通过孵育加载到天然免疫平台OMV中,克服了这一问题。利用omv表面的靶向肽6-Mal- arg - gy - asp (RGD),通过与细胞表面整合素αvβ3结合,增加药物内化,提高了药物在肿瘤部位的蓄积。omv通过降低TAM和Treg,增加CD8+ T和M1,促进DC成熟来逆转免疫抑制性肿瘤微环境(TME),从而刺激免疫应答。DOX和omv的联合治疗弥补了单一治疗(如化疗和免疫治疗)的不足,提高了癌症治疗的疗效,同时有助于选择新的纳米载体和开发有效的治疗方案。
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引用次数: 1
Multifunctional nanoprobe for real-time in vivo monitoring of T cell activation. 实时监测T细胞活化的多功能纳米探针。
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-08-01 DOI: 10.2139/ssrn.4094098
O. Betzer, Yue Gao, Astar Shamul, M. Motiei, T. Sadan, R. Yehuda, Ayelet Atkins, C. Cohen, Mingwu Shen, Xiangyang Shi, R. Popovtzer
Genetically engineered T cells are a powerful new modality for cancer immunotherapy. However, their clinical application for solid tumors is challenging, and crucial knowledge on cell functionality in vivo is lacking. Here, we fabricated a nanoprobe composed of dendrimers incorporating a calcium sensor and gold nanoparticles, for dual-modal monitoring of engineered T cells within a solid tumor. T cells engineered to express a melanoma-specific T-cell receptor and loaded with the nanoprobe were longitudinally monitored within melanoma xenografts in mice. Fluorescent imaging of the nanoprobe's calcium sensor revealed increased intra-tumoral activation of the T cells over time, up to 24 h. Computed tomography imaging of the nanoprobe's gold nanoparticles revealed the cells' intra-tumoral distribution pattern. Quantitative analysis revealed the intra-tumoral T cell quantities. Thus, this nanoprobe reveals intra-tumoral persistence, penetration and functional status of genetically engineered T cells, which can advance T cell-based immunotherapy and promote next-generation live cell imaging.
基因工程T细胞是癌症免疫治疗的一种强有力的新方式。然而,它们在实体肿瘤中的临床应用具有挑战性,并且缺乏关于细胞在体内功能的关键知识。在这里,我们制造了一个由树状大分子组成的纳米探针,结合钙传感器和金纳米颗粒,用于实体肿瘤内工程T细胞的双峰监测。T细胞被改造成表达黑色素瘤特异性T细胞受体,并装载纳米探针,在小鼠黑色素瘤异种移植物中进行纵向监测。纳米探针钙传感器的荧光成像显示,随着时间的推移,肿瘤内T细胞的活化增加,可达24 h。纳米探针的金纳米粒子的计算机断层成像显示了细胞在肿瘤内的分布模式。定量分析显示肿瘤内T细胞数量。因此,这种纳米探针揭示了基因工程T细胞在肿瘤内的持久性、穿透性和功能状态,可以推进基于T细胞的免疫治疗和促进下一代活细胞成像。
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引用次数: 0
Cerium dioxide, a Jekyll and Hyde nanomaterial, can increase basal and decrease elevated inflammation and oxidative stress 二氧化铈是一种具有双重人格的纳米材料,可以增加和减少炎症和氧化应激
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-07-01 DOI: 10.1016/j.nano.2022.102565
Robert A. Yokel PhD , Marsha L. Ensor MSc , Hemendra J. Vekaria PhD , Patrick G. Sullivan PhD , David J. Feola PharmD, PhD , Arnold Stromberg PhD , Michael T. Tseng PhD , Douglas A. Harrison PhD

It was hypothesized that the catalyst nanoceria can increase inflammation/oxidative stress from the basal and reduce it from the elevated state. Macrophages clear nanoceria. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Inflammatory responses were quantified by IL-1β level, arginase activity, and RT-qPCR and metabolic changes and oxidative stress by the mito and glycolysis stress tests (MST and GST). Morphology was determined by light microscopy, macrophage phenotype marker expression, and a novel three-dimensional immunohistochemical method. Nanoceria blocked IL-1β and arginase effects, increased M0 cell OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness. M2-like cells had greater volume than M0 macrophages. The results are overall consistent with the hypothesis.

假设催化剂纳米粒可以从基础状态增加炎症/氧化应激,从升高状态减少炎症/氧化应激。巨噬细胞清除纳米细胞。为了验证这一假设,我们将M0(非极化)、M1-(经典活化、促炎)和m2样(选择性活化、调节性表型)的RAW 264.7巨噬细胞暴露在纳米细胞中。通过IL-1β水平、精氨酸酶活性和RT-qPCR量化炎症反应,通过mito和糖酵解应激试验(MST和GST)量化代谢变化和氧化应激。形态学通过光镜、巨噬细胞表型标记表达和一种新的三维免疫组织化学方法来确定。纳米粒阻断了IL-1β和精氨酸酶的作用,增加了M0细胞向M2表型的OCR和GST,并改变了多个M1和M2样细胞的端点向M0水平。m1样细胞体积更大,圆度更小。m2样细胞体积大于M0巨噬细胞。结果总体上与假设一致。
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引用次数: 3
Correlative imaging to resolve molecular structures in individual cells: Substrate validation study for super-resolution infrared microspectroscopy 相关成像分析单个细胞分子结构:超分辨率红外微光谱底物验证研究
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-07-01 DOI: 10.1016/j.nano.2022.102563
Agnes Paulus PhD , Sahana Yogarasa BSc , Mustafa Kansiz PhD , Isak Martinsson PhD , Gunnar K. Gouras MD, PhD, Professor , Tomas Deierborg PhD, Professor , Anders Engdahl PhD , Ferenc Borondics PhD , Oxana Klementieva PhD

Light microscopy has been a favorite tool of biological studies for almost a century, recently producing detailed images with exquisite molecular specificity achieving spatial resolution at nanoscale. However, light microscopy is insufficient to provide chemical information as a standalone technique. An increasing amount of evidence demonstrates that optical photothermal infrared microspectroscopy (O-PTIR) is a valuable imaging tool that can extract chemical information to locate molecular structures at submicron resolution. To further investigate the applicability of sub-micron infrared microspectroscopy for biomedical applications, we analyzed the contribution of substrate chemistry to the infrared spectra acquired from individual neurons grown on various imaging substrates. To provide an example of correlative immunofluorescence/O-PTIR imaging, we used immunofluorescence to locate specific organelles for O-PTIR measurement, thus capturing molecular structures at the sub-cellular level directly in cells, which is not possible using traditional infrared microspectroscopy or immunofluorescence microscopy alone.

近一个世纪以来,光学显微镜一直是生物学研究中最受欢迎的工具,最近产生了具有精细分子特异性的详细图像,达到了纳米尺度的空间分辨率。然而,光显微镜作为一种独立的技术不足以提供化学信息。越来越多的证据表明,光学光热红外微光谱(O-PTIR)是一种有价值的成像工具,可以提取化学信息,在亚微米分辨率上定位分子结构。为了进一步研究亚微米红外微光谱在生物医学应用中的适用性,我们分析了基质化学对在不同成像基质上生长的单个神经元获得的红外光谱的贡献。为了提供一个相关的免疫荧光/O-PTIR成像的例子,我们使用免疫荧光定位特定的细胞器进行O-PTIR测量,从而直接在细胞中捕获亚细胞水平的分子结构,这是使用传统的红外显微光谱或免疫荧光显微镜无法实现的。
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引用次数: 4
Fabrication of tumor targeting rare-earth nanocrystals for real-time NIR-IIb fluorescence imaging-guided breast cancer precise surgery 实时NIR-IIb荧光成像引导乳腺癌精准手术的肿瘤靶向稀土纳米晶体制备
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-07-01 DOI: 10.1016/j.nano.2022.102555
Kang-Liang Lou BA , Pei-Yuan Wang PhD , Rui-Qin Yang MA , Yi-Yang Gao MA , Hai-Na Tian MA , Yong-Ying Dang BA , Yang Li PhD , Wen-He Huang BA , Min Chen PhD , Xiao-Long Liu PhD , Guo-Jun Zhang MD, PhD

The near-infrared fluorescence imaging has been integrated into the operating room to guide tumor resection, potentially reducing the positive margin rates in breast-conserving surgery (BCS). Relative to the widely used first near-infrared fluorescence imaging, imaging in the second near-infrared (NIR-II) region possesses higher contrast and deeper tissue penetration, particularly in the NIR-IIb window, offering many new opportunities for imaging-guided BCS. Here, we fabricated the c(RGDfC) functionalized erbium-based rare-earth nanoparticles (ErNPs@cRGD) with superior optical property in NIR-IIb region. Owing to deeper tissue penetration and efficient tumor targeting, ErNPs@cRGD-based NIR-IIb fluorescence imaging achieved enhanced signal-to-background ratios in tumor visualization, which was able to guide more complete tumor resection, identify multiple microtumors and distinguish malignant lesions from normal tissues in various mice models. Based on these, this NIR-IIb imaging strategy for surgical navigation can significantly reduce positive margin rates and improve prognosis, laying a foundation for the clinical resection of breast cancer.

近红外荧光成像已被纳入手术室指导肿瘤切除,可能降低保乳手术(BCS)的阳性切缘率。相对于广泛使用的第一近红外荧光成像,第二近红外(NIR-II)区成像具有更高的对比度和更深的组织穿透,特别是在NIR-IIb窗口,为成像引导的BCS提供了许多新的机会。在这里,我们制备了c(RGDfC)功能化的铒基稀土纳米粒子(ErNPs@cRGD),在NIR-IIb区具有优异的光学性能。ErNPs@cRGD-based NIR-IIb荧光成像由于具有更深的组织穿透性和高效的肿瘤靶向性,在肿瘤可视化中实现了更高的信本比,在各种小鼠模型中能够指导更完整的肿瘤切除,识别多发微肿瘤,区分恶性病变与正常组织。在此基础上,采用NIR-IIb影像策略进行手术导航,可显著降低阳性切缘率,改善预后,为乳腺癌临床切除奠定基础。
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引用次数: 6
Antioxidant enzymes immobilized on gold and silver nanoparticles enhance DNA repairing systems of rat skin after exposure to ultraviolet radiation 金、银纳米颗粒固定化抗氧化酶增强紫外线照射后大鼠皮肤DNA修复系统
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-07-01 DOI: 10.1016/j.nano.2022.102558
Agnieszka M. Pudlarz Dr , Katarzyna Ranoszek-Soliwoda Dr hab. , Michał S. Karbownik Dr , Ewa Czechowska Dr , Emilia Tomaszewska Dr , Grzegorz Celichowski Prof. , Jarosław Grobelny Prof. , Ewa Chabielska Prof. , Anna Gromotowicz-Popławska Dr hab. , Janusz Szemraj Prof.

The aim of the study was to investigate in vivo whether the application of immobilized superoxide dismutase (SOD) and catalase (CAT) could enhance DNA repairing systems and reduce level of CPD (cyclobutane pyrimidine dimers) and 6-4PP ((6-4) pyrimidine-pyrimidone photoproducts), and whether the immobilization on gold (AuNPs) and silver (AgNPs) nanoparticles affects the outcome. The study presents secondary analysis of our previous research. Three-day application of SOD and CAT in all forms of solution decreased the levels of CPD and 6-4PP boosted by UV irradiation. The mRNA expression level of the nucleotide excision repair (NER) system genes (XPA, XPC, ERCC1, ERCC2, ERCC3, LIG1) increased after application of immobilized and free enzymes. Increased by UV irradiation, p53 mRNA expression level normalized with the enzyme application. In conclusion, application of free and immobilized antioxidant enzymes accelerates removal of harmful effects of UV radiation in the rat skin by increasing expression level of NER genes.

本研究的目的是研究体内应用固定化超氧化物歧化酶(SOD)和过氧化氢酶(CAT)是否能增强DNA修复系统,降低CPD(环丁烷嘧啶二聚体)和6-4PP((6-4)嘧啶-嘧啶光产物)的水平,以及金(AuNPs)和银(AgNPs)纳米颗粒固定化是否影响结果。本研究是对前人研究的二次分析。在所有形式的溶液中施用3 d的SOD和CAT降低了紫外线照射引起的CPD和6-4PP水平。应用固定化酶和游离酶后,核苷酸切除修复(NER)系统基因(XPA、XPC、ERCC1、ERCC2、ERCC3、LIG1) mRNA表达水平升高。在紫外线照射下,p53 mRNA的表达水平随着酶的使用而正常化。综上所述,游离和固定化抗氧化酶的应用通过提高NER基因的表达水平,加速了紫外线辐射对大鼠皮肤有害影响的清除。
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引用次数: 3
A nanotherapy responsive to the inflammatory microenvironment for the dual-targeted treatment of atherosclerosis 一种对炎症微环境有反应的纳米疗法,用于动脉粥样硬化的双靶向治疗
IF 5.4 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-07-01 DOI: 10.1016/j.nano.2022.102557
Ge Li PhD , Fei Xu PhD , Bo Yang MSc , Xinyue Lu MSc , Xiangyu Li PhD , Yanfei Qi PhD , Lesheng Teng PhD , Youxin Li PhD , Fengying Sun PhD , Wenhua Liu PhD

Atherosclerosis remains the main cause of death and disability, as well as a leading cause of coronary arterial disease. Inflammation is one of the pathogenic factors of arteriosclerosis; however, the current treatments based on lowering the level of inflammation in the plaque tissue of patients with atherosclerosis are not clinically used. Herein, we hypothesize that αvβ3 receptor affinity and low pH sensitivity may be regarded as a valid therapeutic strategy for targeting sites of atherosclerosis according to the microenvironments of inflammation. To prove this tentative hypothesis, an acid-labile material polyketal named PK3 was synthesized, and the cRGDfc peptide was used to modify nanoparticles composed of poly(lactide-co-glycolide) (PLGA), lecithin, and PK3, loaded with the anti-atherosclerotic drug rapamycin (RAP). The nanoparticles were prepared using an O/W method and then characterized, which showed an appropriate particle size and fulfilling responsive behaviors. In vitro release studies and stability tests showed that these nanoparticles can be effectively internalized by human umbilical vein endothelial cells (HUVEC), and also show a good in vitro anti-inflammatory effect. After intravenous (i.v.) injection, RGD targeted by pH-responsive nanotherapy (RAP-Nps-RGD) may be accumulated at the plaque site in ApoE−/− mice with atherosclerosis and can effectively attenuate plaque progression compared to other formulations. Moreover, its good safety profile and biocompatibility have been revealed in both in vitro and in vivo estimations. Accordingly, the prospect of nanoparticles responsive to the inflammatory microenvironment for preventing atherosclerotic through inflammation modulation provides great feasibility for the administration of alternate drug molecules to inflamed sites to slow down the process of arteriosclerosis.

动脉粥样硬化仍然是死亡和残疾的主要原因,也是冠状动脉疾病的主要原因。炎症是动脉硬化的致病因素之一;然而,目前基于降低动脉粥样硬化患者斑块组织炎症水平的治疗尚未临床应用。在此,我们假设αvβ3受体亲和性和低pH敏感性可能被认为是根据炎症微环境靶向动脉粥样硬化部位的有效治疗策略。为了证明这一初步假设,我们合成了一种酸不稳定的聚酮材料PK3,并利用cRGDfc肽修饰由聚丙交酯-乙醇酸酯(PLGA)、卵磷脂和PK3组成的纳米颗粒,装载抗动脉粥样硬化药物雷帕霉素(RAP)。采用O/W法制备了纳米颗粒,并对其进行了表征,结果表明纳米颗粒尺寸合适,具有良好的响应特性。体外释放研究和稳定性试验表明,这些纳米颗粒能被人脐静脉内皮细胞(HUVEC)有效内化,并表现出良好的体外抗炎作用。静脉注射后,ph反应性纳米疗法(RAP-Nps-RGD)靶向的RGD可能在ApoE−/−动脉粥样硬化小鼠的斑块部位积累,与其他制剂相比,可以有效地减缓斑块进展。此外,其良好的安全性和生物相容性已在体外和体内试验中得到证实。因此,纳米颗粒对炎症微环境的反应,通过炎症调节来预防动脉粥样硬化的前景,为将替代药物分子施用于炎症部位以减缓动脉硬化过程提供了巨大的可行性。
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引用次数: 4
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