Loading and release of large protein molecules and separation of lanthanides using mesoporous materials

Abstract

Protein therapeutics are promising candidates for disease treatment due to their high specificity and minimal adverse side effects; however, targeted protein delivery to specific sites has proven challenging. Mesoporous silica nanoparticles (MSN) have demonstrated to be ideal candidates for this application, given their high loading capacity, biocompatibility, and ability to protect host molecules from degradation. These materials exhibit tunable pore sizes, shapes and volumes, and surfaces which can be easily functionalized. This serves to control the movement of molecules in and out of the pores, thus entrapping guest molecules until a specific stimulus triggers release. The benefits of using MSN as protein therapeutic carriers will be covered, demonstrating that there is great diversity in the ways MSN can be used to service proteins. Methods for controlling the physical dimensions of pores via synthetic conditions, applications of therapeutic protein loaded MSN materials in cancer therapies, delivering protein loaded MSN materials to plant cells using biolistic methods, and common stimuli-responsive functionalities will be discussed. New and exciting strategies for controlled release of proteins will also be covered. Mesoporous silica nanoparticles (MSN) with enlarged pores were prepared and characterized, and reversibly dissociated subunits of large protein molecules such Concanavalin A were entrapped in the mesopores, as shown by multiple biochemical and material characterizations. When loaded in the MSN, we demonstrated protein stability from proteases and, upon release, the subunits re-associated into active proteins. We have demonstrated a versatile and facile method to load homomeric proteins into MSN with potential applications in enhancing the delivery of large therapeutic proteins. Similarly dissociated Yeast alcohol dehydrogenase (ADH) can be loaded into MSN and regain activity upon release. This shows our method can be extended to multi-subunit enzymes as well as proteins. Adjacent lanthanides are among the most challenging elements to separate, to the extent that current separations materials would benefit from transformative improvement. Ordered mesoporous carbon (OMC) materials are excellent candidates, owing to their small mesh size and uniform morphology. Herein, two OMC materials were physisorbed with bis-(2-ethylhexyl) phosphoric acid (HDEHP) and the relationships between surface areas, pore sizes, and recovery performance were explored using a 152/154Eu radiotracer. The HDEHP-OMC materials displayed higher distribution coefficients and loading capacities than current state-of-the-art materials.