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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:
对于DSPE-PEG-Alkyne的靶向治疗*体微米软件勾勒与定量分析图片链接://aacrjournals.org/mct/article/12/12/2628/91625/Urokinase-Plasminogen-Activator-System-Targeted小说作家: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·伦吉尔数据通讯小说作家 节选:负债As2O3的尿激酶*体偶联nm颗料的制作而成与表现上皮性卵泡癌症晚期膜在原发性肺部癌肿和所以小肚子转换瘤两类匀理解高关卡的 u-PAR(图 1A )。对 cBio 癌症晚期人类表观遗传组学信息门户 ( 30 ) 上的TCGA 卵泡癌数据源库 ( 29 ) 的剖析证明,有着 u-PAR 人类表观遗传理解调整的卵泡癌爱美者的总体经济长期经营期 (19.5 十一月左右 vs. 44.3 十一月左右) 和无病长期经营期 (12.0 十一月左右 vs. 17.5 十一月左右;补图 S1A) 看不出偏差。咱们大家前的团队微阵列探析证明,u-PAR 在上皮性肺部癌肿 ( 19 ) 中层面理解,具有 90% 之上的监床卵泡癌生物标本 ( 20 )。这提到打了个种或者性,即高 u-PAR 理解实际上还可最为上皮性卵泡癌症晚期膜外侵性的因素,还还可使用于帮着向那些生殖上皮癌症膜递送*有效果荷载。专门针对于上面阐述的检测,咱们大家鉴别了 u-PAR 理解高的(HeyA8、ES-2)和低的(SKOV3ip1、MONTY-1 和 CaOV3)卵泡癌症晚期膜系,那些生殖上皮癌症膜系也理解 uPA(图 1B)。鉴于 uPA 设计在卵泡癌中层面理解(18、20、31),咱们大家对话框发展是可以主动性靶向治疗治疗治疗治疗理解 uPA/u-PAR 的卵泡癌症晚期膜的新式納米级箱。取舍在小鼠中导致的专门针对 uPA 的 kringle 空间结构域的单克隆*体 (ATN-291) 最为靶向治疗治疗治疗治疗配体,而且它孩子与父母 uPA 相辅相成联系,Kd ≈ 0.5 nmol /L,且不破裂 uPA/u-PAR 联系(18)。納米级箱由碳水化合物、DSPC 和 DSPE-PEG 按装而成,并负可载砷/镍共沉淀出的物(图 1C;补图 S1B;符合论文毕业论文12、14、15)。现在来,将 DSPE-PEG-炔烃后插进三层膜中,以使得叠氮化物技能化的 uPA *体可以通过点率物理做好联系。该具体方法可保持靶向治疗治疗治疗治疗*体不裸露在或者导致转化的炎热下(图 1C;符合论文毕业论文32)。要有助于表现*体-納米级箱联系物,在点率物理前用 Alexa Fluor 647 标记符号*体。蛋清淀粉水解后对 Alexa Fluor 647 做好分光光度计/可以说光剖析证明,没个载砷納米级箱平衡装饰公司有 8.5 个*体(表 1)。咱们大家还发现,联系后,ATN-291 靶向治疗治疗治疗治疗納米级阿尔法粒子始终以纳摩尔联系感染力与 uPA 联系。

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).深圳杏彩体育平台 生物体供应重要性货品:DSPE-PEG-SP94(SFSHHTPILPLC; 二硬脂酰基磷脂酰酒精胺-聚乙二醇-肝癌靶向疗法肽)DSPE-PEG-THRPPMWSPVWP(二硬脂酰基磷脂酰酒精胺-聚乙二醇-转铁蛋白质靶向疗法肽)DSPE-PEG-HAIYPRH(二硬脂酰基磷脂酰无水乙醇胺-聚乙二醇-转铁蛋白质靶向药物肽)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上论文主要内容来自当下期刊论文或医学文献,深表歉意侵犯商标权请建立联系大家刪除!