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

TL;DR

This study introduces a novel multi-tissue-on-a-chip platform that models vascularized breast tumor and liver microenvironments to analyze nanoparticle transport and toxicity dynamically, aiding in cancer treatment optimization.

Contribution

It is the first to develop a vascularized multi-tissue microenvironment platform for studying nanoparticle transport and toxicity in cancer and liver tissues.

Findings

Breast tumor microenvironments showed 2.62-fold higher vessel porosity.

Permeability increased by 2.35- and 2.77-fold for small and large particles in tumor tissues.

Larger particles had a 5.57-fold higher accumulation rate in breast tumors.

Abstract

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.