Researchers have developed a chip capable of simulating a tumour’s microenvironment and plan to use the new system to test the effectiveness of nanoparticles and drugs that target cancer.
The tumour-microenvironment-on-chip (T-MOC) device will allow researchers to study the complex environment surrounding tumours and the barriers that prevent the targeted delivery of therapeutic agents, said Bumsoo Han, a Purdue University associate professor of mechanical engineering.
Researchers are trying to perfect so-called targeted delivery methods using various agents, including nanometre-size structures, to selectively attack tumour tissue.
According to the Indiana-based university, one approach is to design nanoparticles small enough to pass through pores in blood vessels surrounding tumours but too large to pass though the pores of vessels in healthy tissue. The endothelial cells that make up healthy blood vessels are well organised and have small pores in the tight junctions between them. However, the endothelial cells in blood vessels around tumours 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 tumour,’ Han said in a statement.
However, one complication hindering the success of this strategy is that the pressure of interstitial fluid inside tumours 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 tumour.
New research findings suggest that the T-MOC system is capable of simulating the complex environment around tumours 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 the Journal of Controlled Release in November. The paper was authored by postdoctoral research associate Bongseop Kwak; graduate students Altug Ozcelikkale and Crystal S. Shin; Kinam Park, the Showalter Distinguished Professor of Biomedical Engineering and a professor of pharmaceutics; and Han.
The T-MOC chip is about 4.5cm square and contains microfluidic channels where tumour cells and endothelial cells are cultured. The chip also incorporates extracellular matrix, which is a spongy, scaffold-like material made of collagen found between cells in living tissue.
The new chip is claimed to offer an alternative to conventional experimental methods. Studies using cancer cells in petri plates exclude the complex microenvironment surrounding tumours, and research with animals does not show precisely how proposed therapies might work in people.
However, the T-MOC system has the potential to mimic cancer in humans, Han said.
The researchers tested the technology using human breast cancer and endothelial cells and studied how nanoparticles moved within the microenvironment.
Future work will expand to the study of anticancer drugs. Eventually, the devices might be used to grow tumour cells from patients to gauge the effectiveness of specific drugs in those people.