Researchers create new 'smart' nanocapsule delivery system for use in protein therapy

In what could signal a major advance in protein therapeutics, researchers at the UCLA Henry Samueli School of Engineering and Applied Science have developed a new intracellular delivery platform that uses nanocapsules made up of a single-protein core with a thin polymer shell that can be engineered to either degrade or remain stable based on the cellular environment.

Their research appeared in the December / January 2010 edition of the journal Nature Nanotechnology.

"For proteins in general, it's very difficult to cross the cell membrane. The protease will usually digest it, making stability an issue," said lead study author Yunfeng Lu, a UCLA professor of chemical and biomolecular engineering. "Here, we've been able to use this new technology to stabilize the protein, making it very easy to cross the cell membrane, allowing the protein to function properly once inside the cell. This is one of our biggest achievements."

Nanocapsules are submicroscopic containers composed of an oily or aqueous core - in this case a single protein - surrounded by a thin, permeable polymer membrane roughly several to tens of nanometers thick. The membranes of the nanocapsules used in the new UCLA delivery method can degrade or remain intact depending on the size of the molecular substrates with which their embedded protein must interact.

Non-degradable nanocapsules are more stable, and small molecular substrates can readily diffuse to the protein embedded inside. The capsule's non-degradable skin meanwhile protects the cargo from protease attacks and stabilizes the protein from other factors, like varying temperatures and pH levels.

However, a non-degradable skin may also prevent substrates of larger molecular weight from reaching the embedded protein. In order for the protein to be able to interact with a large substrate, a degradable skin can also be used.