University of Basel researchers have created a direct path for artificial nanocontainers to enter into the nucleus of living cells. They specifically produced biocompatible polymer vesicles that can pass through the pores that decorate the membrane of the cell nucleus.
A big challenge in the field of nanomedicine has been the development of a reliable method of introducing active substances specifically into the cell nucleus. These new tiny nanocontainers that do just that. These nanocontainers can pass through the nuclear pore complexes that control the transport of molecules into and out of the cell nucleus.
Researchers used a trick to direct the artificial nanocontainers through the nuclear pore complexes: "These polymersomes, which are about 60 nanometers in size, are encapsulated by a flexible polymer membrane that mimics natural membranes," explained Cornelia Palivan, co-author of the paper published today in PNAS. "However, they are more robust than lipid vesicles and can be functionalized as needed."
The team also constructed the polymersomes with nuclear localization signals bound to them—giving them an entry ticket into the nucleus. Cells use these signals to differentiate between molecules that need to be transported into the nucleus and those that should be kept out. In this way, the nuclear localization signals are used to disguise the artificial nanocontainers as permissible cargo.
"The presence of nuclear localization signals enables the polymersomes to hijack the cellular transport machinery that delivers cargo through the nuclear pore complexes," Roderick Lim reported. This property is similarly based on nature: "This strategy is also used by some viruses," he added.
The researchers were able to track the path of the polymersomes into the cell nucleus by filling them with different dyes and observing them using various microscopic techniques. This confirmed the successful transport of the artificial nanocontainers into the cell nucleus in vitro as well as in vivo within living cells.