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

Dendrimer nanoparticles for colorectal cancer applications

“…View Article Online DOI: 10.1039/C9TB02289A Efforts can be mane also namely to reduce cytotoxicity and enhance transepithelial transport [37], for interaction with coupling molecules such as natural-based polymers [37], fluorescent probes [37], and an inner hydrophobic core where other molecules can be trapped [66,67]. Among the myriad possibilities, dendrimers can also find applications as imaging agents [66,68,69], and scaffolds for TERM [70].…”

Human‐on‐Leaf‐Chip: A Biomimetic Vascular System Integrated with Chamber‐Specific Organs

“…After the removal of PMMA sheets, the cell samples in each chamber could be acquired by punching the PDMS layer with a biopsy punch and further transferred into other containers gently. [ 39 ]…”

Functionally Graded Biomaterials for Use as Model Systems and Replacement Tissues

“…In another example, microfluidic systems were used to study the efficacy of a colorectal cancer treatment, demonstrating increasing cell death up the concentration gradient. [77] This is a valuable tool for determining both effective dose and diffusive properties of drugs. Alternatively, microfluidic devices can model gradients of cytotoxic chemicals and their dosedependent effect on cells.…”