Protein therapy, or direct replacement of problematic proteins within cells, has been looked into as a possible alternative to gene therapy. Gene therapy is currently used in certain cases to fix the production of defective proteins, but there is a real potential for side effects when messing with one’s DNA. The problem with delivering proteins is that they are often metabolized by the body and few actually get to where they’re needed. Researchers at UCLA have now developed a method to encapsulate proteins within a polymer shell that can provide safe transport to the target therapy site.
The nanocapsules consist of a single-protein core and thin polymer shell anchored covalently to the protein core. Depending on whether degradable or non-degradable crosslinkers are used in synthesizing the nanocapsule, the skin of the capsule is either degradable or non-degradable. This is an important feature since for enzymes with large substrates, or other proteins that need to interact with other proteins inside the cell, a degradable capsule is essential.
Segura notes that the novel nanocapsules can improve current protein therapeutic delivery with regard to several aspects: increased stability of the protein against protease degradation; enhanced cellular internalization; endosomal escape; and the hydrogel capsule allows for the diffusion of small substrates inside the capsule, so if the protein at the core of the capsule is an enzyme the enzyme is able to catalyze a reaction without degrading the capsule.
“The protein cores can be chosen from a vast library of proteins, including enhanced green fluorescent protein, horseradish peroxidase, bovine serum albumin, superoxide dismutase and caspase-3, which makes this a very versatile delivery platform” says Segura. “This method can also be generalized to multiple protein delivery while maintaining low toxicity. Such a multiple protein delivery method has great potential for therapies in which proteins act synergistically or in tandem.”
Image: (Left) Transmission electronic microscopic (TEM) image of single-protein nanocapsules with uniform size distribution (~30 nm in diameter) and (right) a schematic of the nanocapsule consisting of an encased protein and a skin layer of crosslinked polymer network. (Images: Professor Yunfeng Lu, UCLA)
More from Nanowerk: Highly effective single-protein nanocapsules improve prospects for protein therapies…
Abstract in Nature Nanotechnology: A novel intracellular protein delivery platform based on single-protein nanocapsules