The ability of antibodies to recognize specific cancer cells is used in oncology to specifically target these cells with small active agents. Research published in the journal Angewandte Chemie shows that scientists have now built a transport system that even delivers large protein-based drugs into cancer cells. This study demonstrates how proteins can arrive intact at their target, protected from destructive proteases by polymer brushes.

The development of anticancer treatments poses two recurring problems for researchers. An active agent must be able to kill the cells of the body at the root of the cancer, and it must be active in target cancer cells rather than healthy cells. Many medical researchers are therefore working on the concept of cargo packages. The active agent remains protected and conditioned until it reaches the target location, while antibodies that only bind to cancer cells help “find the right place”.

These antibodies recognize specific receptor structures on the outer membrane of cancer cells. They attach to these structures and the cell absorbs the active agent. However, this strategy fails when the active agents are large proteins. Proteins of this type are generally soluble in water and cannot cross the cell membrane. Another problem is caused by the body’s own protease enzymes, which break down transported proteins before they can reach their target location.

Sankaran Thayumanavan and his colleagues at the University of Massachusetts Amherst, USA, have now developed a particular protected nanoscale cargo package, which meets both the requirements of targeted delivery and keeping the cargo intact. They use tiny silicon dioxide beads with a diameter of just 200 nanometers. The surface of these beads is covered with brush-shaped polyethylene glycol (PEG) polymer strands that can be doubly functionalized, resulting in tiny “brush beads”.

The researchers attached the desired active agent protein and antibodies to the polymer bristles using simple click chemistry. The finished bead-shaped packages contain antibodies entirely on the outside, the proteins being safely hidden in the forest of polymer strands.

In addition to being able to transport water-soluble proteins, this type of protein-antibody conjugate (PAC) also offered researchers another potential advantage: the ability to achieve a high protein-to-antibody ratio in this format. They say that, at least in theory, more than 10,000 proteins could be carried by (expensive) antibodies using the researchers’ PACs, unlike the maximum of four active agents per antibody in previous antibody-drug combinations.

The team tested their system on various cell cultures with different antibodies and test proteins. As expected, the proteins reached their targets in the cell and fulfilled their lethal role.

The team’s next steps are to determine whether cargo packages can be protected from body macrophages. However, they are optimistic because the PEG functionalities and surface antibodies are designed for rapid delivery while minimizing clearance by macrophages.

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About the Author

Principal Investigator, Dr. Sankaran Thayumanavan is a professor at the University of Massachusetts Amherst, United States. His group is interested in the chemistry and (bio) physics of supramolecular assemblies in water, reactive nanomaterials and molecular assemblies that deliver biological cargoes to target cells in active forms.

https: //elements.chem.umass.edu /thaigroup /

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