The nuclei of cells in our bodies is where much of the important intracellular processes take place. The genomic code is mostly stored within the nucleus and gene expression is controlled there, so getting drugs inside this most important organelle is a long sought goal of many researchers. Some viruses have been used to deliver therapies, but overall this is often impractical and risky.
Researchers at University of Basel in Switzerland have now developed polymer nanocontainers that can move through the nuclear membrane and into the nucleus, ferrying drugs along.
Nuclear pore complexes are very selective at what they let pass through, controlling the movement of chemical compounds coming and going into the interior. The new nanocontainers pretend to be a naturally occurring and safe compound that the pore complexes are willing to let through.
“These polymersomes, which are about 60 nanometers in size, are encapsulated by a flexible polymer membrane that mimics natural membranes,” said Professor Cornelia Palivan, one of the senior authors of the study appearing in Proceedings of the National Academy of Sciences. “However, they are more robust than lipid vesicles and can be functionalized as needed.”
The polymersomes have special chemical signals attached to them that disguise their true nature and that open up the nuclear membrane to let them pass.
“The presence of nuclear localization signals enables the polymersomes to hijack the cellular transport machinery that delivers cargo through the nuclear pore complexes,” said Roderick Lim, the other senior author of the study. “This strategy is also used by some viruses.”
To verify that these containers actually enter the nucleus, the researchers filled them with a variety of dyes and monitored their progress using various microscopy techniques. In the future, the dyes can be replaced with therapeutic agents that act on the processes within cellular nuclei, potentially helping to overcome a wide range of diseases that currently have limited treatment options.
Study in Proceedings of the National Academy of Sciences: Organelle-specific targeting of polymersomes into the cell nucleus
Via: University of Basel