Harnessing protein power to deliver medicine

The proof-of-concept research could potentially pave the way to develop more accurate delivery of cytotoxic drugs. Commonly used in chemotherapy, they work by killing cells and can cause significant side effects if not delivered to the exact site of the disease they are targeting.

Led by Dr Taylor Szyszka and Associate Professor Yu Heng Lau from the University's School of Chemistry, a team of researchers has developed protein cages which have been able to package a commonly used chemotherapy drug.

Their findings were published today in leading chemistry journal Angewandte Chemie International Edition.

Known by most as a source of nutrition, proteins are essential to our existence in many ways. There are 42 million proteins in every human cell and each protein comprises varying configurations of 20 different amino acids. The characteristics of those amino acids determine a protein's characteristics and function.

"Nearly everything that happens in a cell, from building its protective membranes to producing energy, requires a protein," said Dr Szyszka.

Dr Szyszka and her team research and develop protein cages, groups of identical proteins bound together to form a spherical shell. They focus on encapsulins -- a sub-group of protein cages -- which are highly stable, able to protect their cargo from outside attackers and also prevent its escape.

The encapsulin underpinning this research was first identified, through separate findings by US researchers, in bacteria found in a compost heap in 2019. Dr Szyszka's team re-engineered the newly discovered encapsulin by fusing it to another protein. This prevented the encapsulin from assembling before the drug was added; had that occurred the encapsulin would have been unable to hold or transport drugs.

The researchers then loaded their turbocharged encapsulin with doxorubicin, a chemotherapy drug, and successfully triggered its assembly in vitro, outside a living organism.

"Doxorubicin is a fluorescent drug and the fluorescent signal we detected after loading demonstrated the drug was successfully packaged during our triggered encapsulin assembly," said Dr Szyszka.

"This is a first. Until now it hasn't been possible for encapsulins to efficiently load drugs. Previously this could happen only by pulling encapsulins apart, loading them with a drug and then reassembling them, a messy process which compromises the encapsulin's stability."

The findings mark the very preliminary stages of harnessing encapsulins as a new, precise, drug delivery mechanism. The next stage in this research is to continue protein engineering the encapsulin so it can gravitate to its target.

"It's now all about engineering the shell's exterior so the encapsulin we developed can target specific cells," said Dr Szyszka. "If it holds a drug designed to treat liver disease for instance, we want the encapsulin to find its way to liver cells.

"We've built the car, now we need to learn how to drive it."