TRANSLATIONAL APPLICATIONS OF THERMOSTABLE EXOSHELLS: A DETAILED STUDY

Abstract

The delivery and stabilization of active enzymes remain a challenge for the field of nanotechnology. Thermostable exoshell (tES) is a representative 12 nm NP with an 8 nm interior cavity. In this thesis, we show that the encapsulated enzymes remain highly stable in vitro. Local injection of tES-HRP in vivo, followed by systemic administration of indole-3-acetic acid (a naturally occurring plant hormone) results in complete regression of an orthotropic, triple-negative breast cancer xenograft. Given the importance of oral administration as the preferred mode of delivery, we improved the tES stability with multiple inter-subunit disulfide bonds. In vitro/in vivo results exhibited potential applications for DS-tES as a carrier for oral delivery. Hypothetically, internalizing a substrate within tES would avoid the aggregation and protect the encapsulated substrate from denaturation during lyophilization and storage. Our results exhibited >14-fold enhancement for encapsulated enzyme after lyophilization compared to the free enzyme in different storage temperatures.