Nanoparticle-Mediated Cytoplasmic Delivery of Proteins To Target Cellular

Despite recent advances in nanomaterial-based delivery systems, their applicability as carriers of cargo, especially proteins for targeting cellular components and manipulating cell function, is not well- understood. Herein, we demonstrate the ability of hydrophobic silica nanoparticles to deliver proteins, including enzymesandantibodies,toadiversesetofmammaliancells,includinghumancancercellsandratstemcells,while preserving the activity of the biomolecule post-delivery. Specifically, we have explored the delivery and cytosolic activity of hydrophobically functionalized silica nanoparticleprotein conjugates in a human breast cancer cell line(MCF-7)andratneuralstemcells(NSCs)andelucidatedthemechanismofcytosolictransport.Importantly,the proteins were delivered to the cytosol without extended entrapment in the endosomes, which facilitated the retention of biological activity of the delivered proteins. As a result, delivery of ribonuclease A (RNase A) and the antibodytophospho-Akt(pAkt)resultedintheinitiationofcelldeath.Deliveryofcontrolproteinconjugates(e.g., those containing greenfluorescent protein or goat antirabbit IgG) resulted in minimal cell death, indicating that thecarrier-mediatedtoxicitywaslow.Theresultspresentedhereprovideinsightintothedesignofnanomaterials as protein carriers that enable control of cell function.