August 14, 2006
Microfluidics Device Screens Cancer Drug Activation
A promising new approach to cancer therapy, known as directed enzyme-prodrug therapy, involves administering a drug designed only to be toxic after being chemically activated by an enzyme that is also delivered into the tumor cell. To help drug developers find these so-called prodrugs, researchers at the Georgia Institute of Technology have created a microfluidic reactor that screens large numbers of chemicals for their ability to be activated by the delivered enzyme.
Reporting its work in the journal Biomacromolecules, a team of investigators led by Jim Spain, Ph.D., described their development of silica nanobeads containing immobilized enzymes. The researchers constructed these nanoscale reactors by first linking the enzyme nitrobenzene nitroreductase (NbzA) to a water-soluble polymer known as poly(ethyleneimine), or PEI. The investigators then grew a silica shell around this polymer-enzyme construct, producing porous silica beads with diameters ranging from 500 to 1,000 nanometers that they could use to fill the channels of a microfluidic device.
With the device in hand, the researchers used it to measure activation of several model compounds by the enzyme. Their results showed that the immobilized enzyme could activate the test compounds and that the amount of activation could be easily measured using a standard spectrophotometer, an instrument that measures color change. The researchers note that the enzyme was stable in its encapsulated form, suggesting that it should be possible to entrap a wide variety of enzymes in silica beads for use in high-throughput activation assays.
This work is detailed in a paper titled, “Application of a microfluidic reactor for screening cancer prodrug activation using silica-immobilized nitrobenzene nitroreductase.” Investigators from the Air Force Research Laboratory at Tyndall Air Force Base, Florida, also participated in this study. This paper was published online in advance of print publication. An abstract is available at the journal’s website.