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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:
来源于DSPE-PEG-Alkyne的靶向治疗*体納米系统性营造与研究方法链接转换://aacrjournals.org/mct/article/12/12/2628/91625/Urokinase-Plasminogen-Activator-System-Targeted作家: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·伦吉尔通信设备作家 节选:负债As2O3的尿激酶*体偶联纳米技术粒状的合成视频与表现上皮性卵泡癌人体癌症在原发性恶性肺部肿瘤和各种肚子移转瘤通常情况下一致表示高的水平的 u-PAR(图 1A )。对 cBio 肺部肿瘤遗传染色体组学门户网站 ( 30 ) 上的TCGA 卵泡癌数据显示库 ( 29 ) 的论述介绍表示,患上了 u-PAR 遗传染色体表示改动的卵泡癌患病者的总的野外发展期 (19.5 六三个月大时间 vs. 44.3 六三个月大时间) 和无病野外发展期 (12.0 六三个月大时间 vs. 17.5 六三个月大时间;获取图 S1A) 显眼良好。大家以前的组织化微阵列论述表示,u-PAR 在上皮性恶性肺部肿瘤 ( 19 ) 中长度表示,属于 90% 以上内容的诊疗卵泡癌样本 ( 20 )。这提起好几个种风险性,即高 u-PAR 表示不光能身为上皮性卵泡癌人体癌症肉瘤样癌性的图标,还能应用在专程向等等人体癌症递送*有效果超载负荷。采取上面叙说的实验报告,大家司法鉴定了 u-PAR 表示高的(HeyA8、ES-2)和低的(SKOV3ip1、MONTY-1 和 CaOV3)卵泡癌人体癌症系,等等人体癌症系也表示 uPA(图 1B)。由 uPA 软件在卵泡癌中长度表示(18、20、31),大家企图开发技术能被动靶点表示 uPA/u-PAR 的卵泡癌人体癌症的多技能nm箱。去在小鼠中带来的采取 uPA 的 kringle 的结构域的单克隆*体 (ATN-291) 身为靶点配体,鉴于它与他人 uPA 相辅相成能够 ,Kd ≈ 0.5 nmol /L,而且是也不会损伤 uPA/u-PAR 能够 (18)。nm箱由高胆固醇的食物、DSPC 和 DSPE-PEG 折装而成,并负放有砷/镍共凝固物(图 1C;获取图 S1B;可以基准期刊论文12、14、15)。接下面来,将 DSPE-PEG-炔烃后加入加厚膜中,以加快叠氮化物技能化的 uPA *体能够 弹框物理去能够 。该做法可有效确保靶点*体是也不会裸露在风险引发转化的温度高下(图 1C;可以基准期刊论文32)。要为方便定量介绍*体-nm箱能够 物,在弹框物理以前用 Alexa Fluor 647 标示*体。蛋清电离后对 Alexa Fluor 647 去太阳光的紫外线/明显可见的光论述介绍表示,每一位载砷nm箱一般装饰工程有 8.5 个*体(表 1)。大家还找到,能够 后,ATN-291 靶点nm离子照样以纳摩尔能够 吸引力与 uPA 能够 。

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).石家庄pg电子娱乐游戏app 动物带来了重要性产品设备:DSPE-PEG-SP94(SFSHHTPILPLC; 二硬脂酰基磷脂酰乙酸乙酯胺-聚乙二醇-肝癌靶点肽)DSPE-PEG-THRPPMWSPVWP(二硬脂酰基磷脂酰乙酸乙酯胺-聚乙二醇-转铁蛋清靶向药物肽)DSPE-PEG-HAIYPRH(二硬脂酰基磷脂酰乙酸乙酯胺-聚乙二醇-转铁蛋清靶向药物肽)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之内一篇文章玩法源于四种期刊杂志或医学文献,如遇侵犯肖像权请关系我们的卸载!