Recapitulating solid stress on tumor on a chip for nanomedicine diffusive transport prediction

Abstract

The characteristic mechanical forces at play within tumors include the abnormal solid and fluid stresses. These, together with the increased extracellular matrix (ECM) stiffness, are the major transport barriers affecting the nanomedicine delivery to solid tumors. Due to the elevated pressure within the tumor microenvironment, the transport of nanomedicines through the interstitial space is limited to diffusion. While this particular scenario is central for nanomedicine delivery to solid tumors, it has not been modeled in vitro before. To this end, herein, a tumor-on-a-chip microfluidic device is developed that is capable of recapitulating the solid stress scenario in tumors. This is achieved by integrating a pneumatic actuation to apply compression to the enclosed hydrogel ECM filling medium. Transport studies of model nanoparticles (NPs) across this medium are performed to determine their diffusion. For these NPs, it is demonstrated that their transport is drastically reduced by 65% due to the compression of the ECM gel matrix, reducing its pore size, with only an applied pressure of 4 Pa. The results obtained show that the actuated tumor-on-a-chip device can be used to evaluate the diffusive penetration capability of nanomedicines within a mechanical-constrained microenvironment such that of tumors.