J Control Release. 2021 Apr 22:S0168-3659(21)00190-5. doi: 10.1016/j.jconrel.2021.04.024. Online ahead of print.
The complexity and heterogeneity of the three-dimensional (3D) tumor microenvironment have brought challenges to tumor studies and cancer treatment. The complex functions and interactions of cells involved in tumor microenvironment have led to various multidrug resistance (MDR) and raised challenges for cancer treatment. Traditional tumor models are limited in their ability to simulate the resistance mechanisms and not conducive to the discovery of multidrug resistance and delivery processes. New technologies for making 3D tissue models have shown the potential to simulate the 3D tumor microenvironment and identify the mechanisms underlying the MDR. This review overviews the main barriers against multidrug delivery in the tumor microenvironment and highlights the advances in microfluidic-based tumor models with the success in simulating several drug delivery barriers. It also presents the progress in modeling various genetic and epigenetic factors involved in regulating the tumor microenvironment as a noticeable insight in 3D microfluidic tumor models for recognizing multidrug resistance and delivery mechanisms. Further correlation between the results obtained from microfluidic drug resistance tumor models and the clinical MDR data would open up avenues to gain insight into the performance of different multidrug delivery treatment strategies.