UCLA

Proteins play the most dynamic and diverse roles among all the biomacromolecules in living organisms. With the fast development in biotechnology, protein gains more and more interests for a wide range of applications, such as biochemical synthesis, sensing, environmental protection and medical applications. However, the vulnerable nature of proteins has hindered their boarder applications. Developing vectors and stabilizers that help to more effectively deliver protein therapeutics or stabilize proteins has been an essential theme of the field.

In this dissertation, novel strategies have been developed for protein delivery by a method of in-situ free-radical polymerization or by a self-assembling/ crosslinking approach. Protein nanocapsules made from the in-situ polymerization method were also used building blocks to synthesize protein composites with dramatically enhanced stability. This dissertation research consist with four topics outlined below:

1. Organophosphorus hydrolase (OPH) nanocapsules were synthesized by in-situ free-radical polymerization with enhanced activity and stability. These nanocapsules are highly potent for decontamination, as well as in vivo detoxification of organophosphorus as prophylactics or antidotes.

2. Protein nanocapsules made by the in-situ polymerization technique were used as building blocks to synthesize protein-silica composites through a sol-gel process. The microenvironment around the proteins was engineered through judicious choices of the polymer monomers and the silica precursors, enabling the synthesis robust enzyme composites with high activity for various industry applications.

3. Protein nanocapsules were synthesized by assembling the proteins with self-crosslinking cell penetrating polymer (SCP). Self-crosslinking by disulfide-bond formation within the SCP leads to the formation of robust protein nanocapsules with highly retained activity. These nanocapsules were able to be effectively internalized by cells without significant cytotoxicity, and the protein cargo could be effectively released upon exposure to glutathione that break down the disulfide bonds.

4. Protein nanocapsules with zwitterionic shells were synthesized by a self-assembling approach. The zwitterionic shells protected the nanocapsules from being uptake by macrophages, while such shells could be detached once exposing to a low pH environment. This approach provides a suitable platform towards protein therapeutics with prolonged circulation time with ability of being delivered into the cells.

Overall, this dissertation work provides novel strategies toward better protein-delivery vectors, as well as composites with better protein stability and activity, for a broad range of applications.