Enzymes are biological catalysts that have many promising biomedical applications. However, they are rapidly degraded and can lead to immune responses when administered intravenously, thereby limiting their usefulness in vivo. There is a need for a versatile enzyme-encapsulation strategy to increase the biological half-life and effectiveness of enzymes. We developed two approaches to encapsulate enzymes in nanoporous silica nanoparticles that shield the enzyme from large biomacromolecules while allowing the entrance of small molecules. We hypothesize that our encapsulation methods will improve enzyme stability and eliminate immune responses from the body. In the first approach, we directly modified the surface of the enzyme to generate a silica precursor, then coated it with silica by hydrolyzing tetraethyl orthosilicate (TEOS) followed by conjugating polyethylene glycol (PEG) groups. In the second approach, we used reverse emulsion conditions by dispersing an aqueous solution of enzyme in decane, with CO-520 and hexanol as surfactant and cosurfactant respectively. Then, we added TEOS and base to grow the silica network, followed by conjugation of PEG groups. We used catalase as a model enzyme because its ability to degrade hydrogen peroxide to oxygen has potential applications for the detection of inflammation and radiosensitization of tumors. We encapsulated catalase in silica nanoparticles of approximately 100 nm, as characterized with dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy. We measured catalase activity electrochemically and demonstrated their protection from proteolysis. We radiolabeled the particles with 89Zr to determine their biodistribution in tumor-bearing mice. Finally, we conjugated anti-EpCAM antibodies and demonstrated their targeting against hepatocyte-derived carcinoma cells in vitro. We demonstrated that we encapsulated catalase in nanoporous silica nanoparticles with high activity and optimal protection, along with the ability to conjugate antibodies for targeting properties. We are currently evaluating the potential of this formulation in vivo for the radiosensitization of tumors.

Enzyme encapsulation in porous silica nanoparticles for potential therapeutic applications

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.