Three Dimensional Cell Culture: A Window into Transport of Nanomedicine in Tumor Tissue.

3D cell culture;Nanotechnology;Drug delivery;Cancer treatment;Monte-Carlo simulation;Carbon nanotube;Biomedical Engineering;Engineering;Biomedical Engineering

Wang, YichunXu, Zhen ;

University of Michigan

关键词: 3D cell culture;    Nanotechnology;    Drug delivery;    Cancer treatment;    Monte-Carlo simulation;    Carbon nanotube;    Biomedical Engineering;    Engineering;    Biomedical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/120907/yichunw_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Recent growth in nanotechnology has been accelerating the identification and evaluation of new drug candidates. The development, optimization of nanomedicine and preclinical drug screening is critical but long and expensive. These studies are challenging due to the lack of test platforms that can incorporate sufficient human-relevant physiological complexity for reliable and standardized prediction. Current preclinical models based on animals are expensive and has poor predictivity due to the variety of animals and limitation of imaging technologies. Two-dimensional (2D) cell cultures used in the preclinical phase drug screening cannot adequately restore original cellular behaviors to nanomedicine in three-dimensional (3D) tissues. 3D cell culture models with the ability to independently manipulate microenvironmental factors can be used as a platform, to explore fundamental biological response to novel therapeutic nanoparticles. Transport of nanomedicine through solid tumors can be adequately evaluated in specially prepared 3D cell culture as platform. This is important for validating drug doses and administration regimens required to achieve desired therapeutic effects.In coupling with Monte-Carlo sampling and analysis of conditioned microenvironment, the standardized and uniform-sized liver tumor spheroids culture model in Inverted Colloidal Crystal (ICC) scaffolds can be used to quantitatively identify or validate predictive nanoparticle (NP) transport, while transparency of the platform allowed convenient real-time monitoring with high resolution. This dissertation established the experimental and conceptual framework for quantitative evaluation of NP transport in the tumor tissue ex vivo as a part of drug discovery, and explored a new opportunity of carbon nanotubes as a promising nano-sized carrier for drug delivery. Beside, this platform has been improved to develop patient/disease-specific model for individualized study of drug safety and efficacy or drug–drug interactions with 3D stem cell culture. In this part of dissertation, ICC scaffolds with uniform, controllable porous structure combined with a layer-by-layer (LBL) bone mimetic modification technique served as a platform for engineered stem cells.Overall, this dissertation introduces a promising and standardized 3D cell culture platform as a window to fundamental understanding of nanomedicine, as well as a practical and valuable tool for drug discovery regarding drug delivery and transport through complex 3D tissues.