Fraunhofer Institute for Biomedical Engineering, Department Bioprocessing & Bioanalytics, Joseph-von-Fraunhofer-Weg 1, 66280 Sulzbach (Germany).
biolitec research GmbH, Otto-Schott-Strasse 15, 07745 Jena (Germany).
Eur J Pharm Sci. 2022 Jan 1;168:106046. doi: 10.1016/j.ejps.2021.106046. Epub 2021 Oct 17.
The development of new tumor models for anticancer drug screening is a challenge for preclinical research. Conventional cell-based in vitro models such as 2D monolayer cell cultures or 3D spheroids allow an initial assessment of the efficacy of drugs but they have a limited prediction to the in vivo effectiveness. In contrast, in vivo animal models capture the complexity of systemic distribution, accumulation, and degradation of drugs, but visualization of the individual steps is challenging and extracting quantitative data is usually very difficult. Furthermore, there are a variety of ethical concerns related to animal tests. In accordance with the 3Rs principles of Replacement, Reduction and Refinement, alternative test systems should therefore be developed and applied in preclinical research. The Hen's egg test on chorioallantoic membrane (HET-CAM) model provides the generation of vascularized tumor spheroids and therefore, is an ideal test platform which can be used as an intermediate step between in vitro analysis and preclinical evaluation in vivo. We developed a HET-CAM based intestine tumor model to investigate the accumulation and efficacy of nano-formulated photosensitizers. Irradiation is necessary to activate the phototoxic effect. Due to the good accessibility of the vascularized tumor on the CAM, we have developed a laser irradiation setup to simulate an in vivo endoscopic irradiation. The study presents quantitative as well as qualitative data on the accumulation and efficacy of the nano-formulated photosensitizers in a vascularized intestine tumor model.
开发用于抗癌药物筛选的新肿瘤模型是临床前研究的一个挑战。传统的基于细胞的体外模型，如 2D 单层细胞培养或 3D 球体，允许初步评估药物的疗效，但它们对体内效果的预测有限。相比之下，体内动物模型可以捕捉到药物在体内的系统分布、积累和降解的复杂性，但可视化各个步骤具有挑战性，并且提取定量数据通常非常困难。此外，动物测试还存在各种伦理问题。因此，根据替代、减少和优化的 3R 原则，应开发和应用替代测试系统。鸡胚绒毛尿囊膜（HET-CAM）模型提供了血管化肿瘤球体的生成，因此是一种理想的测试平台，可作为体外分析和体内临床前评估之间的中间步骤。我们开发了一种基于 HET-CAM 的肠道肿瘤模型，用于研究纳米制剂光敏剂的积累和疗效。辐照是激活光毒性效应所必需的。由于 CAM 上血管化肿瘤的良好可及性，我们开发了一种激光辐照装置来模拟体内内窥镜辐照。该研究提供了定量和定性数据，说明纳米制剂光敏剂在血管化肠道肿瘤模型中的积累和疗效。
