Using Red Blood Cells, Lights, and Honey Bee Peptides to Deliver Therapeutic Proteins to Specific Areas in the Body.

The orange-red dye indicates that blood clots are forming in the ears of mice where thrombin is released from light-triggered RBCs. Bar scale, 50 μm. Credit: Adapted from ACS Central Science 2020, DOI: 10.1021 / acscentsci.0c01151

Protein therapy is often stronger and chooses the direction of biochemical targets than other types of drugs, especially small molecules. However, proteins are also more easily degraded by enzymes or cleared from the blood by the kidneys, which limits its clinical use. Now, researchers report on ACS Science Center has engineered red blood cell carriers (RBCs) that release therapeutic proteins when stimulated by light, with the help of honey bee peptides.

Because protein drugs are unstable in the body, they need to be stored at a high level, which can cause side effects. Scientists have been trying to protect protein therapy from degradation by relying on carriers, such as liposomes, nanoparticles and RBCs. But it is challenging for operators to release their cargo at the right place and time. Brianna Vickerman, David Lawrence and colleagues want to work with RBC engineers to release therapeutic proteins in specific areas of the body when triggered by light wavelengths.

Researchers attribute peptides, called melittin, to RBCs cell membranes. The component of the European honey bee venom, melittin usually causes RBC rupture. But the team changed the peptide so that it would be done only when illuminated by a specific wavelength of light. As proof of concept, researchers loaded thrombin – a blood clotting enzyme used to prevent excessive bleeding – into engineered and injected RBCs into mice. They then highlight the light in a small area of ​​each rat’s ear and examine the tissue parts. Analysis shows that blood clotting associated with thrombin is only at the luminous site. Strategies can prove useful for releasing light proteins, peptides and nuclei sour therapeutics of a variety of lipid-based carriers, researchers think.

Reference: December 9, 2020, ACS Science Center,
DOI: 10.1021 / acscentsci.0c01151

The authors claim funding from the Eshelman Institute for Innovation and the American Heart Association.

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