Protein-based therapy is a relatively new way to treat a range of maladies, from inflammation, lysosomal storage diseases, certain cerebrovascular disorders and cancers. The technique involves introducing proteins into host cells but progress in the field has been difficult for lack of efficient delivery methods.

The new protein delivery technique developed by Vincent Rotello and colleagues involves assembling a protein payload on the surface of an oil droplet using gold nanoparticles, so generating supramolecular capsules (NPSCs). Incubating biological cells with the NPSCs then results in the protein entering directly into the cytosols of the cells thanks to hydrophobic interactions between the capsules and cell membrane. The cytosol, also known as intracellular fluid, is the liquid matrix found inside all living cells.

In their experiments, Rotello and colleagues showed that they could rapidly and efficiently deliver the biomedically important enzyme Caspase-3 into the cytosol of HeLa cells using NPSCs. Caspase-3 belongs to a family of delicate enzymes that would easily inactivate during delivery and the fact that the researchers have succeeded in delivering it into cells is proof that their technique works. The team has also managed to deliver green fluorescent protein (GFP) into the biological cells and follow its movement using spectroscopy and flow cytometry techniques.

The researchers formed their NPSCs using a commercial homogenizer, commonly used by dentists to prepare fillings. They mixed gold nanoparticles, oil and water together and then briefly homogenized the ensemble. The NPSCs were then incubated with protein or Caspase-3 at room temperature for 10 minutes.

"There are numerous examples in which such in vitro protein delivery would be useful," says Rotello. "For example, in cell biology studies and tissue engineering. On the in vivo side, our system has the potential to revolutionize protein-based therapies thanks to its efficiency and simplicity."

Indeed, the team says that it is now already testing its technique for in vitro tissue engineering applications. "We are also beginning in vivo experiments to see how well these work in animal models," Rotello told "We expect that we will need to tune the system for these studies as protein release rates will be very important."

The present work is published in ACS Nano DOI: 10.1021/nn402753y.

Further reading

Large surface hole in mesoporous silica capsules expands cargo options (Feb 2012)
Surface hydrophilicity of carbon nanotube array affects protein delivery (Jul 2011)
Delivering proteins with nanoscale precision (Jul 2005)
Striped nanoparticles enter cells with ease (Jun 2008)
Pluronic nanocapsule carries molecules into living cells (Jun 2009)