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This paper presents the development of a vascularized breast tumor andhealthy or tumorigenic liver microenvironments-on-a-chip connected in series.This is the first description of a vascularized multi tissue-on-a-chipmicroenvironment for modeling cancerous breast and cancerous/healthy livermicroenvironments, to allow for the study of dynamic and spatial transport ofparticles. This device enables the dynamic determination of vesselpermeability, the measurement of drug and nanoparticle transport, and theassessment of the associated efficacy and toxicity to the liver. The platformis utilized to determine the effect of particle size on the spatiotemporaldiffusion of particles through each microenvironment, both independently and inresponse to the circulation of particles in varying sequences ofmicroenvironments. The results show that when breast cancer cells were culturedin the microenvironments they had a 2.62-fold higher vessel porosity relativeto vessels within healthy liver microenvironments. Hence, the permeability ofthe tumor microenvironment increased by 2.35- and 2.77-fold compared to ahealthy liver for small and large particles, respectively. The ECM accumulationrate of larger particles was 2.57-fold lower than smaller particles in ahealthy liver. However, the accumulation rate was 5.57-fold greater in thebreast tumor microenvironment. These results are in agreement with comparablein vivo studies. Ultimately, the platform could be utilized to determine theimpact of the tissue or tumor microenvironment, or drug and nanoparticleproperties, on transport, efficacy, selectivity, and toxicity in a dynamic, andhigh throughput manner for use in treatment optimization.

In Vitro Vascularized Liver and Tumor Tissue Microenvironments on a Chip for Dynamic Determination of Nanoparticle Transport and Toxicity