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对瘤微环境的重新定位和增强瘤向药物输送

Ilaria Biancacci¹, Daniele De Santis^1,2, Elena Rama¹

¹RWTH Aachen University, Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Forckenbeckstrasse 55, 52074, Aachen, Germany.

Advanced therapeutics

|October 8, 2024

概括

塔莫西芬 (TMX) 不能改善纤维化瘤中的药物输送. 在胰腺和乳腺癌模型中的研究表明,TMX未能增强纳米粒子积累或改变瘤微环境.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
瘤微环境 (TME) 研究研究

背景情况:

纤维性瘤中密集的 stromal 基质阻碍了药物输送.
托莫西芬 (TMX) 是一种雌激素受体调节剂,可以重新编程瘤微环境 (TME) 并减少脱.
将TMX重新用作TME重塑剂可以增强纳米粒子药物输送.

研究的目的:

为了调查TMX,在自由和纳米配方形式,可以重塑TME.
在胰腺管腺癌和三阴性乳腺癌模型中评估TMX在改善纳米颗粒瘤积累方面的有效性.
评估TMX对关键TME参数的影响,如血管化, perfusion 和原密度.

主要方法:

使用PANC-1和4T1小鼠模型,分别用于胰腺癌和乳腺癌.
管理自由和纳米配方的TMX.
评估了使用体内成像进行临床阶段Cy7标记的核心交叉连接聚合物微粒 (CCPM) 的瘤积累.
进行了瘤组织的基因病理免疫光分析.

主要成果:

基线CPM积累在PANC-1瘤 (16.7%的IDg-1),高于在4T1瘤 (11.0%的IDg-1).
无论是自由的还是纳米配方的TMX在任何瘤模型中都没有显著改善CCPM的输送.
TMX治疗没有显著改变血管化,输液,巨细胞透,原蛋白密度或原蛋白纤维厚度.

结论:

在PANC-1和4T1小鼠模型中,TMX治疗并不能使TME受益.
在这些模型中,TMX不会增强纳米颗粒的瘤向药物输送.
需要进一步的研究来确定有效的TME调节策略,以改善癌症纳米药物输送.

关键词:

药物输送是药物输送的过程.纳米医学是一种纳米医学.聚合物微粒是多聚合物的.塔莫西芬 (Tamoxifen) 是一种瘤微环境是一个微环境.

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