Protein Nanocapsule for Drug Delivery
Technology: University of California researchers are investigating a protein scaffold system for molecular transport, namely, the E2 protein of Bacillus stearothermophilus in the pyruvate dehydrogenase complex. This model system has many features that make it attractive as a generalizable scaffold for drug delivery. Although it is a large complex, it self-assembles from smaller subunits that are easily heterologously expressed in E. coli. Since it is derived from a thermophilic organism, it is quite stable. In contrast to other self-assembling spherical complexes (such as icosahedral viral capsids) the core can accommodate large foreign peptides and proteins that are genetically engineered to the surface while retaining its self-assembling capabilities. This allows targeting regions to be easily incorporated into the system.
UC researchers will engineer self-assembled protein complexes to encapsulate and transport drug molecules with varying chemical properties. To engineer this complex for solubilization and delivery of drug molecules, the characteristics of the protein will be investigated. Molecular modeling of the structure will aid the selection of amino acid targets. UC researchers will also test cell targeting and internalization by peptides and proteins. One important advantage of this system over other caged protein systems for drug delivery is the ability to genetically use foreign peptides and proteins without critically affecting the self-assembly behavior of the icosahedral core. UC researchers will also determine the molecular parameters in the self-assembly of the engineered protein scaffold. Understanding the reasons behind this protein self-assembly and stability is key to the development of an engineered complex based on human E2. This aim will investigate the important interactions which promote the self-assembly and themostability of the E2 protein. Application: Proposed uses are in the area of drug formulation and delivery: (1) hydrophobic drug encapsulation; and (2) definition of internal and external surface properties of a nanocapsule for drug delivery. The basis of designing biomaterials for broader applications: (1) cross-linked to form bigger complex to serve as a drug depot, etc. (2) attachment of inorganic nanoparticles to the interior of the cage, together with surface functionality, for applications such as medical imaging or intracellular trafficking probes.
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