Tumor-on-a-chip Mimicking The Kidney Cancer Metastasis To The Liver For Evaluating Anti-tumor Treatment Of Drug-loaded Nanoparticles

Metastasis is one of the most important factors that lead to poor prognosis in cancer patients,and effective suppression of the growth of primary cancer cells in a metastatic site is paramount in averting cancer progression.However,there is a lack of biomimetic three-dimensional(3D)in vitro models that can closely mimic the continuous growth of metastatic cancer cells in an organ-specific extracellular microenvironment(ECM)for assessing effective therapeutic strategies.In this metastatic tumor progression model,kidney cancer cells(Caki-1)and hepatocytes(i.e.,Hep LL cells)were co-cultured at an increasing ratio from 1:9 to 9:1 in a decellularized liver matrix(DLM)/gelatin methacryloyl(Gel MA)-based biomimetic liver microtissue in a microfluidic device.Via this model,we successfully demonstrated a linear anti-cancer relationship between the concentration of anti-cancer drug 5-Fluorouracil(5-FU)and the percentage of Caki-1 cells in the co-culture system(R~2=0.89).Furthermore,the Poly(lactide-co-glycolide)(PLGA)-poly(ethylene glycol)(PEG)-based delivery system showed superior efficacy to free 5-FU in killing Caki-1 cells.In this study,we present a novel 3D Tumor-on-a-chip model mimicking the progression of kidney cancer cells metastasized to the liver for predicting treatment efficacy.Taken together,our study proved that the tumor progression model based on metastasis-on-a-chip with organ-specific ECM would provide a valuable tool for rapidly assessing treatment regimens and developing new chemotherapeutic agents.