Imitation Virus Could be Best Way to Administer Drugs to Cells

New method may improve treatment for a number of diseases.

French scientists recently determined a method to imitate viruses in order to administer drugs to cells more efficiently, according to a new study. To achieve this, the team used 2 polymers they designed, which notably can self-assemble or dissociate, depending on the conditions.

While biotechnical advances have inspired a wealth of compounds with therapeutic potential, many of these compounds remain inactive until they enter the cell through the difficult-to-penetrate lipid membrane. The challenge, therefore, is to find transfer solutions that can cross this barrier.

By imitating the ability of viruses to penetrate into cells, chemists in the Laboratoire de Conception et Application de Molecules Bioactives (CNRS/Universite de Strasbourg) sought to design particles capable of releasing macromolecules that are only active inside cells.

In order to achieve this, the particles must remain stable in the extracellular medium, must be able to bind to the cells so that they be internalized, and they must be more fragile inside the cells so that they can release their content. The scientists were successful in creating a chemical virus that meets these conditions by using the 2 polymers designed by the team.

The first polymer, pGi-Ni2+, serves as a substrate for the proteins that bind to it. The second, πPEI, encapsulates this assembly thanks to its positive charges, which bind to the negative charges of pGi-Ni2+.

The particles obtained are able to recognize the cell membrane and bind to it. This binding leads to the nanoparticle surrounded by a membrane fragment to enter the intracellular compartment called the endosome.

Although they remain stable outside the cell, the assemblies are attacked by the acidity that is abundant within this new environment. The drop in pH allows the πPEI to burst the endosome, releasing its content of active compounds.

In using this method, scientists were successful in concentrating enough active proteins within the cells to achieve a notable biological effect. In this way, scientists were able to deliver a protein called caspase 3 into cancer cell lines, killing 80% of cells infected with the disease.

The in vitro results are encouraging, particularly since this “chemical virus” only becomes toxic at a dose ten times higher than that used during the study. Preliminary results in the mouse have not yielded any results of excess mortality.

However, elimination by the body of the two polymers remains an open question. The next step for scientists is to test the method in other animals and humans. In the meantime, this system will serve as a research tool to vectorize recombinant and chemically modified proteins into cells.

Long-term goals include the use of this method in the administration of drugs to cells in order to combat deadly diseases such as cancer. The methodology could lead to breakthroughs in new drugs for patients.