Organelles perform a range of necessary functions in cells, making them an important target for drug development. According to a new study, University of Basel scientists have now succeeded in integrating artificial organelles into the cells of living zebrafish embryos, an approach with potential for treating a range of diseases. Their results were published online today in Nature Communications.
The artificial organelles are designed as tiny capsules that form spontaneously in solution from polymers and can enclose macromolecules such as enzymes. The ones created for this study contain a peroxidase enzyme that only acts in response to specific molecules entering the capsule. To control the substances that enter, chemically modified natural membrane proteins are incorporated into the wall of the capsule. These pores only open in response to a glutathione concentration beyond a certain threshold.
The researchers chose zebrafish embryos to test out these artificial organelles because they are transparent, allowing them to track the implants under a microscope. When the organelles were injected, they were engulfed by macrophages, thus making their way into the embryos. The peroxidase enzyme was activated in response to hydrogen peroxide produced by the macrophages entering the protein gates.
"In this study, we showed that the artificial organelles, which are inspired by nature, continue to work as intended in the living organism, and that the protein gate we incorporated not only works in cell cultures but also in vivo," explained Toma Einfalt, the first author of the article.
A potential use for these artificial organelles could be in carrying enzymes into the cell that convert a pharmaceutical into an active substance that gets released “on-demand”, allowing treatment to be delivered in response to specific pathologic conditions.
Image: These are artificial organelles in the scavenger cells of a zebrafish that were made visible by a fluorescent reaction. The fluorescence only occurs when the enclosed peroxidase enzyme is activated and reacts hydrogen peroxide produced by the scavenger cells. The researchers have thus provided evidence that the artificial organelles function in vivo. Image courtesy of the University of Basel, Department of Pharmaceutical Sciences