A new intracellular delivery platform using nanocapsules has been developed by researchers at the UCLA Henry Samueli School of Engineering and Applied Science.
Protein therapy - the delivery of healthy proteins directly into human cells to replace malfunctioning proteins - is considered one of the most direct and safe approaches for treating diseases. But its effectiveness has been limited by low delivery efficiency and the poor stability of proteins, which are frequently broken down and digested by cells' protease enzymes before they reach their intended target.
AdvertisementNow the boffins claim that the delivery system can be engineered to either degrade or remain stable based on the cellular environment.
Their research appears Dec. 29 in the January 2010 edition of the journal Nature Nanotechnology and is currently available online.
"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.
When the protein nanocapsule is taken in by the cell, it will stay within the endosome initially.
Endosomes generally have lower pH levels than the outside cellular environment; the lower pH triggers the degradation of the polymer skin layer, releasing the protein cargo intracellularly.
You May Also Like