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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:
整体设计DSPE-PEG-Alkyne的靶向药物*体纳米技术整体倡导与定量分析环节://aacrjournals.org/mct/article/12/12/2628/91625/Urokinase-Plasminogen-Activator-System-Targeted诗人: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·伦吉尔电力诗人 节选:过载As2O3的尿激酶*体偶联纳米级颗粒肥料的分解成与表现上皮性子宫癌細胞在原发性肺部癌肿和各个腰腹转到瘤通常情况下一致传达具体方法出高环境承载力水平的 u-PAR(图 1A )。对 cBio 肝癌什么是表观遗传组学地坪漆 ( 30 ) 上的TCGA 子宫癌数值库 ( 29 ) 的参与研究分析表面,患上了 u-PAR 什么是表观遗传传达具体方法出修改的子宫癌患有的环境承载力孤岛求生存期 (19.5 十一月时间 vs. 44.3 十一月时间) 和无病孤岛求生存期 (12.0 十一月时间 vs. 17.5 十一月时间;多补图 S1A) 清晰稍差。咱们此前的组织组成部分微阵列探讨表面,u-PAR 在上皮性肺部癌肿 ( 19 ) 中非常传达具体方法出,是指 90% 以内的监床子宫癌标本采集 ( 20 )。这提供 半个种概率性,即高 u-PAR 传达具体方法出仅仅能否当作上皮性子宫癌細胞外侵性的象征,还能否适用专门采取向以上細胞递送*行之有效超载负荷。在中间介绍的實驗,咱们签别了 u-PAR 传达具体方法出高的(HeyA8、ES-2)和低的(SKOV3ip1、MONTY-1 和 CaOV3)子宫癌細胞系,以上細胞系也传达具体方法出 uPA(图 1B)。考虑到 uPA 机系统在子宫癌中非常传达具体方法出(18、20、31),咱们对话框的开发就能够及时靶点传达具体方法出 uPA/u-PAR 的子宫癌細胞的新式微米箱。选定 在小鼠中生成的采取 uPA 的 kringle 组成部分域的单克隆*体 (ATN-291) 当作靶点配体,会因为它人和人之间 uPA 密封运用,Kd ≈ 0.5 nmol /L,或者都不是被破坏 uPA/u-PAR 运用(18)。微米箱由高胆固醇的食物、DSPC 和 DSPE-PEG 组装流水线而成,并负放有砷/镍共奠定物(图 1C;多补图 S1B;规范专著12、14、15)。收起来,将 DSPE-PEG-炔烃后插进双层线路膜中,以驱动叠氮化物功能性化的 uPA *体参与单击事件催化工业参与运用。该具体方法可狠抓靶点*体都不是爆漏在概率产生转化的耐高温下(图 1C;规范专著32)。因为更好地定性研究分析*体-微米箱运用物,在单击事件催化工业此前用 Alexa Fluor 647 标示*体。血清油脂水解后对 Alexa Fluor 647 参与紫外光/可看见光参与研究分析表面,各个载砷微米箱年均装饰性有 8.5 个*体(表 1)。咱们还表明,运用后,ATN-291 靶点微米再生颗粒己经以纳摩尔运用沟通协调能力与 uPA 运用。

DSPE-PEG-Alkyne

DSPE-PEG-Alkyne

DSPE-PEG-Alkyne

译文翻译: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).渭南pg电子娱乐游戏app 生物技术带来了有关物品:DSPE-PEG-SP94(SFSHHTPILPLC; 二硬脂酰基磷脂酰甲醇胺-聚乙二醇-肝癌靶向治疗肽)DSPE-PEG-THRPPMWSPVWP(二硬脂酰基磷脂酰工业乙醇胺-聚乙二醇-转铁淀粉酶靶向疗法肽)DSPE-PEG-HAIYPRH(二硬脂酰基磷脂酰甲醇胺-聚乙二醇-转铁淀粉酶靶向治疗肽)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不低于稿件东西起源以及期刊杂志或文章,如果发现侵权案请取得联系公司全部删除!