Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine

TLDR

Traditional 2D in vitro and animal models fail to emulate the 3D tissue complexity, compromising translation to clinical success. The study develops a tumor‑on‑a‑chip model to evaluate precision nanomedicine delivery and validate drug‑loaded nanoparticle efficacy in a gradient. The model uses microfluidic biomimetic chambers with a CMCht/PAMAM nanoparticle gradient, and viability assays with live imaging confirm dose‑response effects. Gene‑expression analysis showed down‑regulation of MMP‑1, Caspase‑3, and Ki‑67, indicating the model’s potential for personalized precision nanomedicine.

Abstract

Awareness that traditional two-dimensional (2D) in vitro and nonrepresentative animal models may not completely emulate the 3D hierarchical complexity of tissues and organs is on the rise. Therefore, posterior translation into successful clinical application is compromised. To address this dearth, on-chip biomimetic microenvironments powered by microfluidic technologies are being developed to better capture the complexity of in vivo pathophysiology. Here, we describe a "tumor-on-a-chip" model for assessment of precision nanomedicine delivery on which we validate the efficacy of drug-loaded nanoparticles in a gradient fashion. The model validation was performed by viability studies integrated with live imaging to confirm the dose-response effect of cells exposed to the CMCht/PAMAM nanoparticle gradient. This platform also enables the analysis at the gene expression level, where a down-regulation of all the studied genes (MMP-1, Caspase-3, and Ki-67) was observed. This tumor-on-chip model represents an important development in the use of precision nanomedicine toward personalized treatment.