The “Tumor microenvironment” (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions between TME constituents has hampered in-depth research into the TME.
Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner using tumor cell-line, tumor spheroid, and patient-derived organotypic culture. This work demonstrated morphological and gene expression changes in tumor cells when co-cultured with stromal cells (e.g., endothelial cells and fibroblasts). Furthermore, our tumor-on-a-chip enabled direct observation of vascularized 3D in vitro tumor tissues with pathologically relevant conditions. This work also covered various nanoparticle (NP) (e.g., HDL mimetic NPs and cationic polymer NPs) and drug delivery through vasculature and investigated the role of autophagy in tumor and tumor-stroma interaction. To overcome inherent fabrication and usage limitations in conventional soft lithographic polydimethylsiloxane (PDMS) based microfluidic platform, this work additionally suggested standardized and mass producible injection molded microfluidic chip for pharmaceutical investigations requiring robust high-throughput and high contents assays.
We believed that this in vitro biomimetic model and experimental concepts; from cell-line culture to patient-derived organotypic culture will help to shed light on the complex biology of the TME and provide the most effective and efficient tool for developing precision personalized medicine that combined with targeted agents and conventional cancer therapy in terms of high-throughput and high-contents screening.