A Dynamic 3D Tumor Spheroid Chip Enables More Accurate Nanomedicine Uptake Evaluation

Abstract

Nanomedicine has brought great advances for drug delivery by improving the safety and efficacy of pharmaceuticals. However, many nanomaterials showing good distribution property in vitro often display poor cellular uptake during in vivo administration. Current cellular uptake research models are mainly based on the traditional 2D culture system, which is a single layer and static system, thus the results cannot accurately reflect the distribution of nanoparticles (NPs) in vivo. In the present study, a multiple tumor culture chip (MTC-chip) is constructed to mimic solid tumor and dynamic fluid transport, in order to better study NPs penetration in vitro. Cellular uptake of mesoporous silica particles (MSNs) is evaluated using the 3D tumor spheroids on chip, and it is found that: 1) continuous administration results in larger MSNs penetration than transient administration at the same dose; 2) the size effect on cellular uptake is less significant than reported by previous in vitro studies; and 3) pretreatment with hyaluronidase (HAase) enhances the tumor penetration of large-size MSNs.