Pathologist slide image of breast cancer cells (Cecil Fox, National Cancer Institute
2 November 2017. Biomedical engineers designed a device that simulates the supportive environment in which tumors grow, and in tests was shown to work as well as lab mice for assessing cancer drugs. Researchers at Purdue University in West Lafayette, Indiana are publishing their findings in a paper scheduled to appear in the November 2017 issue of the Journal of Controlled Release (paid subscription required).
The team from Purdue’s Biotransport Phenomena Laboratory, led by engineering professor Bumsoo Han, is seeking better tools for early testing of drug candidates that today often rely on lab cultures or small animals. While these tests can be helpful, they often do not adequately recreate the environment in which the new drugs are asked to work, and thus can provide misleading results.
This problem is particularly acute, say the authors, in tumor microenvironments, the surrounding network of cells and proteins that support the unchecked growth of solid cancer tumors. Recreating a tumor microenvironment in lab animals is difficult, because of the complex factors in humans that do not often occur in the same way with smaller and simpler mammals.
To address this problem, Han and colleagues are developing microfluidic chip devices, often called labs-on-a-chip, with fine channels etched in plastic and lined with cells like those found in the human tissue and organs. The researchers call these devices tumor-microenvironments-on-chips, or T-Mocs, designed to simulate the regions in human tissues and organs with solid tumors. T-Mocs are created in three dimensions made with extracellular matrix material, the framework matter supporting living cells.
In their paper, the Purdue team tested T-Mocs simulating breast cancer with two types of breast cancer cells. The devices, about 4.5 centimeters square, simulate the interstitial flow of fluid that transports cells through tissues, as well as plasma clearance, the filtering of drugs through the tumor. The researchers tested two formulations of the chemotherapy drug Doxorubicin, in its original small-molecule form and as nanoscale particles in hyaluronic acid. In the devices, both types of breast cancer cells took up the Doxorubicin, although the original small-molecule form of the drug penetrated the tumor cells better than the nanoparticles, which the researchers attribute to the smaller form of the original drug.
In comparing the results to similar tests with conventional petri-dish lab cultures, the researchers found the T-Moc devices were more likely to show resistance developing to Doxorubicin than in ordinary lab cultures. In later tests with lab mice, the team found the T-Mocs performed similarly to mice, with resistance developing to the drug in both mice and chips. The results suggest devices like T-Mocs could substitute for mice, making discovery of new drugs a somewhat simpler process.
These proof-of-concept findings suggest T-Mocs are feasible for drug discovery and testing, and the researchers plan to expand their tests to include pancreatic and prostate cancers. The long-term goal of the project is to create a platform for personalized medicine, where cancer cells taken from individuals’ biopsies can populate the chips to test alternative therapies in the lab before giving them to patients.
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