...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Archives of Pharmacal Research >Evaluation of interstitial protein delivery in multicellular layers model
【24h】

Evaluation of interstitial protein delivery in multicellular layers model

机译：评估间质蛋白在多细胞层模型中的传递

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The limited efficacy of anticancer protein drugs is related to their poor distribution in tumor tissue. We examined interstitial delivery of four model proteins of different molecular size and bioaffinity in multicellular layers (MCL) of human cancer cells. Model proteins were tumor necrosis factor-related apoptosis-including ligand (TRAIL), cetuximab, RNase A, and IgG. MCLs were cultured in Transwell inserts, exposed to drugs, then cryo-sectioned for image acquisition using fluorescence microscopy (fluorescent dye-labeled TRAIL, RNase A, IgG) or immunohistochemistry (cetuximab). TRAIL and cetuximab showed partial penetration into MCLs, whereas RNase A and IgG showed insignificant penetration. At 10-fold higher dose, a significant increase in penetration was observed for IgG only, while cetuximab showed an intense accumulation limited to the front layers. PEGylated TRAIL and RNase A formulated in a heparin-Pluronic (HP) nanogel showed significantly improved penetration attributable to increased stability and extracellular matrix binding, respectively. IgG penetration was significantly enhanced with paclitaxel pretreatment as a penetration enhancer. The present study suggests that MCL culture may be useful in evaluation of protein delivery in the tumor interstitium. Four model proteins showed limited interstitial penetration in MCL cultures. Bioaffinity, rather than molecular size, seems to have a positive effect on tissue penetration, although high binding affinity may lead to sequestration in the front cell layers. Polymer conjugation and nanoformulation, such as PEGylation and HP nanogel, or use of penetration enhancers are potential strategies to increase interstitial delivery of anticancer protein drugs.
机译：抗癌蛋白药物的有限功效与其在肿瘤组织中的分布不均有关。我们检查了人类癌细胞多细胞层（MCL）中分子大小和生物亲和力不同的四种模型蛋白的间质传递。模型蛋白是肿瘤坏死因子相关的凋亡，包括配体（TRAIL），西妥昔单抗，RNase A和IgG。 MCL在Transwell插入物中培养，接触药物，然后冷冻切片，使用荧光显微镜（荧光染料标记的TRAIL，RNase A，IgG）或免疫组化（西妥昔单抗）进行图像采集。 TRAIL和西妥昔单抗显示出部分渗透入MCL，而RNase A和IgG显示出微不足道的渗透。在高10倍的剂量下，仅IgG的渗透率显着增加，而西妥昔单抗显示出强烈的积累，仅限于前层。肝素-Pluronic（HP）纳米凝胶中配制的PEG化TRAIL和RNase A分别由于增加的稳定性和细胞外基质结合而显着改善了穿透力。紫杉醇预处理作为渗透增强剂可显着增强IgG的渗透。本研究表明，MCL培养可用于评估肿瘤间质中的蛋白传递。四种模型蛋白在MCL培养物中显示出有限的间隙渗透。尽管高亲和力可能导致前细胞层的隔离，但生物亲和力而不是分子大小似乎对组织渗透具有积极作用。聚合物缀合和纳米制剂（例如PEG化和HP纳米凝胶）或使用渗透增强剂是增加抗癌蛋白药物间隙递送的潜在策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号