Purdue University researchers have developed a chip capable of simulating a tumor’s “microenvironment” to test the effectiveness of nanoparticles and drugs that target cancer. The new tumor-microenvironment-on-chip (T-MOC) will allow researchers to study the complex environment surrounding tumors and the barriers that prevent targeted delivery of therapeutic agents, said Bumsoo Han, a Purdue associate professor of mechanical engineering. Researchers are trying to perfect “targeted delivery” methods using various agents, including an assortment of tiny nanometer-size structures, to selectively attack tumor tissue. The endothelial cells that make up healthy blood vessels are well organized and have small pores in the tight junctions between them. So one approach is to design nanoparticles that are small enough to pass through pores in the blood vessels surrounding tumors but too large to pass though the pores of vessels in healthy tissue. The problem: the endothelial cells in blood vessels around tumors are irregular and misshapen, with larger pores in the gaps between the cells. “It was thought that if nanoparticles were designed to be the right size they could selectively move toward only the tumor,” Han said. But the pressure of “interstitial fluid” inside tumors is greater than that of surrounding healthy tissue. This greater pressure pushes out most drug-delivery and imaging agents, with only a small percentage of them reaching the target tumor.
Now, new research findings suggest that the T-MOC system is capable of simulating the complex environment around tumors and providing detailed information about how nanoparticles move through this environment. Such information could aid efforts to perfect targeted delivery methods. The findings are detailed in a research paper appearing online this month and will be published in a print edition of the Journal of Controlled Release in November. The T-MOC chip is about 4.5 centimeters (1.8 inches) square and contains “microfluidic” channels where tumor cells and endothelial cells are cultured. The chip also incorporates extracellular matrix – a spongy, scaffold-like material made of collagen found between cells in living tissue.