Zombie-like Cells Can Help Quicken Drug Discovery

Researchers are using zombie-like cells that behave normally on the outside but are filled with magnetic particles inside. They are being used to screen potential drugs from natural products.

This method uses magnetic nanoparticles that are coated with biological cell membrane as a lure to get pharmacologically active compounds from natural organisms such as fungi and compounds from plants. It can sort through hundreds and even thousands of compounds found in the natural product quickly. It usually just lasts for a few days and it typically can take weeks or even months if traditional screening methods are used.

This was done in the labs of Dr. Lukasz M. Ciesla, UA assistant professor of biological sciences, and Dr. Yuping Bao, UA associate professor of chemical and biological engineering. The lead author is Dr. Jennifer Sherwood, a former researcher in Bao's lab who earned her doctorate from UA in 2018.

This solves one of the main problems and bottlenecks in drug discovery from natural products," Ciesla said. "It dramatically speeds up the process of the identification of new drug leads."

Around 70 percent of drugs that are approved by the federal Food and Drug Administration was first discovered in nature but teasing out the possible chemical compounds from them is time-consuming. Pharmaceutical research has turned to studies of synthesized chemical compounds that are tuned for a purpose. However, nature is diverse in the compounds that it has and creates, and the plants produce compounds that are designed for a biological response.

"Plants produce chemicals with structures we cannot possibly imagine," Ciesla said.

Natural samples are complex. An extract of the plant produces chemical compounds and finding one that shows a promise in the pharmacological world is done by isolating and screening the compounds individually. The newly discovered method uses ionic solvents to lure out the innards of a cell and wrapping its shell around iron oxide nanoparticles. They are placed into a plant extract.

This can then keep the function of the transmembrane proteins that act as receptors for active compounds, which then binds them to the coated nanoparticles. It is like a zombie that is still moving even though it is dead, the cell is no longer active, yet its membrane is still functioning. This advantage can help differentiate it from computational methods that simulate chemical interaction in one, static state.

"We have the receptor in its natural environment behaving the way it normally behaves in a cell," he said.

The method was discovered at the University of Alabama, could help quicken a normally laborious task that usually slows drug discovery, according to findings in a paper published in the journal Nanoscale.

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