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基于DSPE-PEG-Alkyne的靶向抗体纳米系统构建与表征
发布时间:2025-06-25     作者:kx   分享到:
基本概念DSPE-PEG-Alkyne的靶向疗法*体奈米系统的倡导与研究方法链接搜索://aacrjournals.org/mct/article/12/12/2628/91625/Urokinase-Plasminogen-Activator-System-Targeted著者:张依林; 希拉里·A·肯尼; 埃尔登·P·斯温德尔; 阿尼尔班·K·米特拉; 帕特里克·L·汉金斯; 理查德·W·安; 卡佳·格温; 安德鲁·P·马扎尔; 托马斯·V·奥哈洛伦; 恩斯特·伦吉尔通迅著者 节选:过载As2O3的尿激酶*体偶联纳米技术粒子的获得与定量分析上皮性子宫恶性肿癌核在原发性肿癌和很多肚子转意瘤通常情况下平滑理解爱高综合水平的 u-PAR(图 1A )。对 cBio 肝癌什么是什么是基因组学门户网 ( 30 ) 上的TCGA 子宫癌数据统计库 ( 29 ) 的概述揭示,都身患 u-PAR 什么是什么是基因理解爱影响的子宫癌病员的综合存在期 (19.5 三个月大时间左右 vs. 44.3 三个月大时间左右) 和无病存在期 (12.0 三个月大时间左右 vs. 17.5 三个月大时间左右;及时补充维生素图 S1A) 严重不佳。各位以往的机构微阵列设计揭示,u-PAR 在上皮性肿癌 ( 19 ) 中高理解爱,是指 90% 大于的临床实践子宫癌标本采集 ( 20 )。这体统阐述一个多种能能性,即高 u-PAR 理解爱不仅能能能有所成为上皮性子宫恶性肿癌核侵蚀性性的标志图案,还能能应用于采取性向这血内部膜核递送*可行反力。对今天说明的工作,各位评定了 u-PAR 理解爱高的(HeyA8、ES-2)和低的(SKOV3ip1、MONTY-1 和 CaOV3)子宫恶性肿癌核系,这血内部膜核系也理解爱 uPA(图 1B)。原因 uPA 体统在子宫癌中高理解爱(18、20、31),各位检测设计也可以主动地靶点理解爱 uPA/u-PAR 的子宫恶性肿癌核的复合型納米箱。选购在小鼠中出现的采取 uPA 的 kringle 结构设计域的单克隆*体 (ATN-291) 有所成为靶点配体,毕竟它人与人 uPA 紧密联系可以通过,Kd ≈ 0.5 nmol /L,而且也也不会破环 uPA/u-PAR 可以通过(18)。納米箱由胆固、DSPC 和 DSPE-PEG 拼装而成,并负可载砷/镍共结晶物(图 1C;及时补充维生素图 S1B;参考使用选取医学论文12、14、15)。收起来,将 DSPE-PEG-炔烃后进到这一领域双层玻璃膜中,以增强叠氮化物功用化的 uPA *体可以通过点开电学上的展开可以通过。该方式可保证 靶点*体也也不会暴漏在能能使得转化的持续高温下(图 1C;参考使用选取医学论文32)。只为以及表现*体-納米箱可以通过物,在点开电学上的以往用 Alexa Fluor 647 标志*体。蛋清电离后对 Alexa Fluor 647 展开太阳光的紫外线/隐约不可见光概述揭示,每一家载砷納米箱大概设计装饰有 8.5 个*体(表 1)。各位还得知,可以通过后,ATN-291 靶点納米塑料颗粒依然以纳摩尔可以通过亲和与 uPA 可以通过。

DSPE-PEG-Alkyne

DSPE-PEG-Alkyne

DSPE-PEG-Alkyne

原文翻译:Synthesis and characterization of urokinase antibody–conjugated nanobins loaded with As2O3Epithelial ovarian cancer cells homogeneously express elevated levels of u-PAR in the primary tumor and all abdominal metastasis (Fig. 1A). Analysis of the TCGA ovarian cancer database (29) at the cBio cancer genomics portal (30) showed that patients with ovarian cancer with u-PAR gene expression alterations had a significantly worse overall (19.5 vs. 44.3 months) and disease-free survival (12.0 vs. 17.5 months; Supplementary Fig. S1A). And our previous tissue microarray studies demonstrated that u-PAR is highly expressed in epithelial tumors (19) including more than 90% of clinical ovarian cancer specimens (20). This raises the possibility that high u-PAR expression might not only function as a marker of aggressiveness for epithelial ovarian cancer cells but could also be used to specifically deliver a therapeutic payload to those cells. For the experiments described below, we identified ovarian cancer cell lines with high (HeyA8, ES-2) and with low (SKOV3ip1, MONTY-1, and CaOV3) u-PAR expression, all of which also express uPA (Fig. 1B). Because the uPA system is highly expressed in ovarian cancer (18, 20, 31), we sought to develop novel nanobins that would actively target uPA/u-PAR–expressing ovarian cancer cells. A monoclonal antibody raised against the kringle domain of uPA in mice (ATN-291) was chosen as a targeting ligand as it binds tightly to human uPA with a Kd ≈ 0.5 nmol/L and does not disrupt uPA/u-PAR binding (18). The nanobins were assembled from cholesterol, DSPC, and DSPE-PEG, and loaded with an arsenic/nickel coprecipitate (Fig. 1C; Supplementary Fig. S1B; refs. 12, 14, 15). Next, DSPE-PEG-alkyne was postinserted into the bilayer to facilitate the conjugation of the azide-functionalized uPA antibody using click chemistry. This method ensures that the targeting antibodies are not exposed to potentially denaturing high temperatures (Fig. 1C; ref. 32). To facilitate characterization of antibody–nanobin conjugates, the antibody was labeled with Alexa Fluor 647 before click chemistry. UV/Vis analysis of Alexa Fluor 647 after proteolysis showed that the arsenic-loaded nanobins were decorated with an average of 8.5 antibodies per nanobin (Table 1). We also found that, after conjugation, the ATN-291–targeted nanoparticle still bound uPA with nanomolar binding affinity (data not shown).杭州杏彩体育平台 生物技术提拱涉及到的类产品:DSPE-PEG-SP94(SFSHHTPILPLC; 二硬脂酰基磷脂酰工业乙醇胺-聚乙二醇-肝癌靶向治疗肽)DSPE-PEG-THRPPMWSPVWP(二硬脂酰基磷脂酰无水乙醇胺-聚乙二醇-转铁淀粉酶靶点肽)DSPE-PEG-HAIYPRH(二硬脂酰基磷脂酰乙酸乙酯胺-聚乙二醇-转铁核蛋白靶点肽)DSPE-PEG-ferroceneDSPE-PEG-WGADSPE-PEG-StreptavidinDSPE-PEG-BSADSPE-PEG-LysozymeDSPE-PEG-PLLDSPE-PEG-HeparinDSPE-PEG-InsulinDSPE-PEG-LectinsDSPE-PEG-lactoferrinDSPE-PEG-GalactoseDSPE-PEG-DextranDSPE-PEG-ChitosanDSPE-PEG-MannoseDSPE-PEG-GlucoseDSPE-PEG-HADSPE-PEG-Alginate左右稿件知识來源各种杂志或论文资料,知悉侵犯商标权请找各位删掉!