  This paper presents the development of a vascularized breast tumor and
healthy or tumorigenic liver microenvironments-on-a-chip connected in series.
This is the first description of a vascularized multi tissue-on-a-chip
microenvironment for modeling cancerous breast and cancerous/healthy liver
microenvironments, to allow for the study of dynamic and spatial transport of
particles. This device enables the dynamic determination of vessel
permeability, the measurement of drug and nanoparticle transport, and the
assessment of the associated efficacy and toxicity to the liver. The platform
is utilized to determine the effect of particle size on the spatiotemporal
diffusion of particles through each microenvironment, both independently and in
response to the circulation of particles in varying sequences of
microenvironments. The results show that when breast cancer cells were cultured
in the microenvironments they had a 2.62-fold higher vessel porosity relative
to vessels within healthy liver microenvironments. Hence, the permeability of
the tumor microenvironment increased by 2.35- and 2.77-fold compared to a
healthy liver for small and large particles, respectively. The ECM accumulation
rate of larger particles was 2.57-fold lower than smaller particles in a
healthy liver. However, the accumulation rate was 5.57-fold greater in the
breast tumor microenvironment. These results are in agreement with comparable
in vivo studies. Ultimately, the platform could be utilized to determine the
impact of the tissue or tumor microenvironment, or drug and nanoparticle
properties, on transport, efficacy, selectivity, and toxicity in a dynamic, and
high throughput manner for use in treatment optimization.
