An international team including researchers from the University of Santiago de Compostela has described a mechanism to bring bioactive agents into the cell using boron compounds that are capable of disordering water molecules and dehydrating the load they carry. In this way, they can cross the cell membrane without damaging it and deliver the cargo, which may be of great interest for administering drugs.

One of the great challenges in drug design is introducing water-soluble molecules into the cell since the cell membrane is a semi-permeable barrier that these types of substances cannot easily cross. To overcome it, experts have been using different artificial vehicles such as polymers, lipids and some types of peptides that successfully carry their cargo inside the cell.

To date, all of these carriers have an amphiphilic structure  (with one end water-bound and the other lipid-bound), allowing them to transiently mask their charge in a hydrophobic envelope to break through the lipid membrane. But this strategy has its limitations: sometimes this same behavior can damage the membrane, and in other cases, amphiphilic compounds show poor solubility, which can limit their effectiveness.

Now researchers from the Singular Center for Research in Biological Chemistry and Molecular Materials (CiQUS) of the University of Santiago de Compostela, in collaboration with scientists from the Jacobs University of Bremen (Germany), have developed a new class of molecular vehicles to administer drugs that it transcends amphiphilic dogma. The progress is published in an open access article in Nature.

The new carriers are clusters of boron atoms with a spherical shape, negative charge and excellent solubility in water. The key lies in their superchaotropic nature, a property that allows them to mess up water molecules and thus dehydrate the charge they carry in order to pass through the hydrophobic membrane.

“We have identified an entirely new class of vehicles that could be used to deliver different drugs into cells. Superchaotropic anions are a new tool, totally different from those that existed to date, to be able to internalize hydrophilic substances in the cell whose potential has just begun to be explored”, highlights Guilia Salluc from CiQUS, one of the first two co-authors of the study.

In particular, a boron and bromine compound (B 12 Br 12 2- ) has been found to be the optimal candidate for this new class of superchaotropic boron carriers. It interacts with the molecules to be transported in a totally new way, without the need to aggregate with it or have to encapsulate it.

The new strategy serves to efficiently deliver a wide variety of bioactive substances, from small molecules to larger peptides. These boron complexes can successfully transport them into living cells, as the ICFO group, led by Professor Javier Montenegro, has shown. 

“We anticipate that the broad and distinct delivery spectrum of our superchaotropic carriers will be the starting point for conceptually distinct cell-biological, neurobiological, physiological, and pharmaceutical studies,” the authors conclude in their paper.

Source: SINC