At first glance, drilling holes into cells may seem unconventional and perhaps counterproductive. But for a Johns Hopkins materials scientist, it’s a strategy that could someday allow the delivery of life-saving medication directly into those infinitesimal structures.
Supported by the National Institute of Health’s National Institute of General Medical Studies, Kalina Hristova and researchers at Tulane University and The University of Bucharest in Romania are creating those minuscule holes in an attempt to understand nanopores, nanometer-scaled openings or channels naturally formed in cells by proteins.
“Our goal is to unlock new ways of generating these holes and using them to expedite treatment for serious conditions such as cancer,” said Hristova, a core researcher of the Johns Hopkins Institute for NanoBioTechnology. “We are drilling those holes to discover how pores form, so we can then use them to get medication where it will be most effective.”
Nanopores allow large polar molecules—which make up many of today’s medicines—to infiltrate cells. Polar molecules dissolve in water but are blocked from entering the cell by its fatty plasma membrane, meaning the medicine can’t reach its target: the cell’s inner protein. Currently, only a few non-polar drugs, such as aspirin, are small enough to pass through a cell’s outer wall without nanopore assistance.
“They don’t reach the site of action,” explains Hristova, “and very few drugs can go through the cell membrane. This research is for drugs that are large and polar, not like aspirin.”
The first step is finding out how tiny proteins, called peptides, gather to form the pores. Hristova will trigger the tiny holes by changing the pH or acidic levels surrounding cells, looking at the movement of peptides into pores. She wants to identify and control the exact assembly of peptides, which will enhance the pore formation process.
“Once we have formed the pores, we work to understand what keeps them together,” says Hristova.
The researchers believe that revealing the characterization and stabilization of nanopores will pave the way for their use in biotechnology and medicine.
“We hope that what we learn will inform best practices for medicine delivery to patients fighting cancer or other life-threatening conditions,” she says.