Microfluidic design of tumor vasculature and nanoparticle uptake by cancer cells

Abstract

The most challenging phase in the clinical translation of drugs is the complex process of screening various drugs and evaluating their therapeutic effects in vitro and in vivo. Microfluidic models have been recognized as an interesting alternative to animal models for drug screening. Enhanced permeation and retention (EPR) effect is one of the most widely used standard for drug delivery in solid tumors with high vascular density and active angiogenesis. The nascent blood vessels in the tumor vicinity have large gaps between the endothelial junctions which allow nanoparticles to pass through them, resulting in selective extravasation and passive accumulation in the tumor regions. In this study, an attempt has been made to mimic some of the physiological characteristics in solid tumors such as endothelial gap junctions, obstructed blood vessels and EPR using a microfluidic platform for drug screening under dynamic culture conditions. The microfluidic chip was fabricated using soft lithography technique. Numerical simulations were performed to analyze the flow patterns inside the chip. Fluorescent gold nanoclusters (Au NCs) were synthesized and their accumulation in the tumor cells cultured inside the microfluidic chip was studied. The experimental results showed an increased uptake of Au NCs in the cells near the endothelial gap junctions in comparison to the cells away from the junctions. The observations in the study correlated with the leaky nature of the tumor vasculature, owing to the enhancement of vascularization and thereby EPR effect. Hence, the fabricated microfluidic device has the potential of minimizing the number of pre-clinical trials using animal models, allowing easier drug screening.