Abstract：
BACKGROUND: Classical two-dimensional (2D) cell culture as a drug or nanoparticle test system only poorly recapitulates in vivo conditions. Animal studies are costly, ethically controversial, and preclude large-scale testing.
RESULTS: We established a three-dimensional (3D) tissue slice air-liquid interface (ALI) culture model for nanoparticle testing. We developed an optimized procedure for the reproducible generation of large sets of tissue slices from tumor xenografts that retain their tissue architecture. When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture. While nanoparticle efficacies between cell culture and the tissue slice model overall correlated, the tissue slice model also identified particularly suitable candidates whose efficacy was underestimated in 2D cell culture and had already been shown in previous in vivo studies.
CONCLUSIONS: The ex vivo 3D tissue slice ALI culture model is a powerful system that allows the effective evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment. It is comparably inexpensive, time-saving, and follows the 3R principle, while allowing the identification of critical nanoparticle properties and optimal candidates for in vivo applications.
RESULTS: We established a three-dimensional (3D) tissue slice air-liquid interface (ALI) culture model for nanoparticle testing. We developed an optimized procedure for the reproducible generation of large sets of tissue slices from tumor xenografts that retain their tissue architecture. When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture. While nanoparticle efficacies between cell culture and the tissue slice model overall correlated, the tissue slice model also identified particularly suitable candidates whose efficacy was underestimated in 2D cell culture and had already been shown in previous in vivo studies.
CONCLUSIONS: The ex vivo 3D tissue slice ALI culture model is a powerful system that allows the effective evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment. It is comparably inexpensive, time-saving, and follows the 3R principle, while allowing the identification of critical nanoparticle properties and optimal candidates for in vivo applications.
摘要：
背景：作为药物或纳米颗粒测试系统的经典二维（2D）细胞培养仅很少能概括体内条件。动物研究是昂贵的，道德上有争议，并排除大规模测试。
结果：我们建立了用于纳米颗粒测试的三维（3D）组织切片气-液界面（ALI）培养模型。我们开发了一种优化的程序，用于从保留其组织结构的肿瘤异种移植物中重复生成大量组织切片。当用于分析基于化学修饰的聚乙烯亚胺（PEI）的纳米颗粒以递送siRNA或DNA时，在转染效率和细胞毒性之间的差异观察到纳米颗粒比在2D细胞培养更清楚。虽然细胞培养和组织切片模型之间的纳米颗粒功效总体相关，组织切片模型还确定了特别合适的候选者,其功效在2D细胞培养中被低估,并且已经在先前的体内研究中得到证实.
结论：离体3D组织切片ALI培养模型是一种强大的系统，可在完整的组织环境中有效评估生物纳米颗粒的功效和生物相容性。它相对便宜，节省时间,并遵循3R原则，同时允许识别关键的纳米颗粒特性和体内应用的最佳候选物。本文受版权保护。保留所有权利。
结果：我们建立了用于纳米颗粒测试的三维（3D）组织切片气-液界面（ALI）培养模型。我们开发了一种优化的程序，用于从保留其组织结构的肿瘤异种移植物中重复生成大量组织切片。当用于分析基于化学修饰的聚乙烯亚胺（PEI）的纳米颗粒以递送siRNA或DNA时，在转染效率和细胞毒性之间的差异观察到纳米颗粒比在2D细胞培养更清楚。虽然细胞培养和组织切片模型之间的纳米颗粒功效总体相关，组织切片模型还确定了特别合适的候选者,其功效在2D细胞培养中被低估,并且已经在先前的体内研究中得到证实.
结论：离体3D组织切片ALI培养模型是一种强大的系统，可在完整的组织环境中有效评估生物纳米颗粒的功效和生物相容性。它相对便宜，节省时间,并遵循3R原则，同时允许识别关键的纳米颗粒特性和体内应用的最佳候选物。本文受版权保护。保留所有权利。
