Proteins with medical potential

Proteins are the micro-machines of life that keep our cells running smoothly. Hironori Yamazoe wants to use them to treat disease too. At the National Institute of Advanced Industrial Science and Technology, in Osaka, Japan, he is developing methods to combine a variety of fragile natural proteins into stable and tiny solid-state medical devices. He reports a “proof of concept” example in the journal Biomaterials.

The proof of concept particle is designed to tackle the problem of chemicals known as “reactive oxygen species” (ROS), which are a major cause of damage to cells in many diseases, including cardiovascular disease. The oxidative damage caused by ROS is the reason behind the widely known interest in “antioxidant” chemicals in foods and cosmetics, which may counteract the effects of ROS.

Yamozoe’s particle is based on the natural stability of a protein found in the blood called albumin. Albumin is used to carry and stabilize an enzyme—superoxide dismutase—that degrades one of the most active forms of ROS. The final crucial building blocks are antibody molecules that can bind to the cells that most actively secrete ROS. Drugs can also be added for delivery to the targeted cells, such as the antioxidant diapocynin used in the proof of concept work. These components are fabricated into a flat and thin microparticle that can capture and “treat” several cells at the same time (see image). Changing the antibody molecules could change the type of cells that are targeted.

Yamazoe explains that combining proteins into multi-protein particles, fibers, or films has thus far been limited by the proteins’ fragility. Crucial structural and functional characteristics can be lost when the molecules are combined.

“Due to this limitation, previous work has not taken full advantage of what proteins can do,” says Yamazoe. “I decided to try to construct solid-state protein microparticles without losing the native functions.” Some researchers have tackled this challenge by combining the proteins with other materials. Yamazoe suggests that his own protein-only approach might be more compatible with the body, raising fewer safety concerns. He has found construction methods that can achieve stability while retaining functions, by joining a variety of different proteins into cross-linked structures.

At this early stage of development, the system has been tested using only cultured cells as targets. The activity of the enzyme reduces the level of ROS species that have been secreted by and are found surrounding treated cells by approximately 70%. Additionally, the diapocynin can diffuse out of the microparticle, enter the cells, and decrease the production of ROS by 67%.

“The next crucial step, a study in live animals, is now underway,” says Yamazoe. Success in these animal studies will hopefully lead the research on toward clinical trials and real medical applications.

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Yamazoe, H.: "Multifunctional protein particles for medical applications," Biomaterials (2018)