Laboratory of Precision NanoMedicine, Tel Aviv University, Tel Aviv 69978, Israel.
Nanoscale. 2020 Jan 23;12(3):1894-1903. doi: 10.1039/c9nr09572a.
The failure of cancer therapies in clinical settings is often attributed to the lack of a relevant tumor model and pathological heterogeneity across tumor types in the clinic. The objective of this study was to develop a robust in vivo tumor model that better represents clinical tumors for the evaluation of anti-cancer therapies. We successfully developed a simple mouse tumor model based on 3D cell culture by injecting a single spheroid and compared it to a tumor model routinely used by injecting cell suspension from 2D monolayer cell culture. We further characterized both tumors with cellular markers for the presence of myofibroblasts, pericytes, endothelial cells and extracellular matrix to understand the role of the tumor microenvironment. We further investigated the effect of chemotherapy (doxorubicin), nanomedicine (Doxil®), biological therapy (Avastin®) and their combination. Our results showed that the substantial blood vasculature in the 3D spheroid model enhances the delivery of Doxil® by 2.5-fold as compared to the 2D model. Taken together, our data suggest that the 3D tumors created by simple subcutaneous spheroid injection represents a robust and more vascular murine tumor model which is a clinically relevant platform to test anti-cancer therapy in solid tumors.
在临床环境中，癌症疗法的失败通常归因于缺乏相关的肿瘤模型和临床肿瘤类型之间的病理异质性。本研究的目的是开发一种更能代表临床肿瘤的稳健体内肿瘤模型，以评估抗癌疗法。我们通过注射单个球体成功地开发了一种基于 3D 细胞培养的简单小鼠肿瘤模型，并将其与常规使用的从 2D 单层细胞培养中注射细胞悬浮液的肿瘤模型进行了比较。我们进一步用肌成纤维细胞、周细胞、内皮细胞和细胞外基质的细胞标志物对两种肿瘤进行了特征描述，以了解肿瘤微环境的作用。我们进一步研究了化疗（多柔比星）、纳米医学（多柔比星脂质体）、生物疗法（阿瓦斯汀）及其组合的作用。我们的结果表明，与 2D 模型相比，3D 球体模型中大量的血管系统将 Doxil®的递送增加了 2.5 倍。总之，我们的数据表明，通过简单的皮下球体注射产生的 3D 肿瘤代表了一种稳健且更具血管的小鼠肿瘤模型，这是一个临床相关的平台，可用于测试实体瘤中的抗癌疗法。
