Recent decades have led to the development of numerous pharmacological treatments for human disease. Though these treatments have largely proven effective, many are limited by their non-specificity; their inability to distinguish healthy from diseased tissue. Nanoscale delivery systems have the potential to maximize therapeutic outcomes by enabling target specific delivery of these therapeutic molecules. Among the materials investigated for nanoscale delivery applications, mesoporous silica nanoparticles (MSNs) have garnered particular interest due to their high structural stability, tunable synthesis, versatile chemistry, and biological inertness. However, this material, like many of the materials that have been investigated for use as molecular carriers, exhibit poorly controlled intracellular localization leading to sequestration in degradative cellular pathways and limiting the efficacy of their payloads. Numerous proteins, particularly bacterial toxins, have evolved mechanisms to subvert the degradative mechanisms of the cell. Herein, we demonstrate a strategy for shunting intracellular delivery of encapsulated cargoes from these pathways by modifying MSNs with the well-characterized bacterial toxin Cholera toxin subunit B (CTxB). This approach makes possible the delivery of sensitive biomolecular cargoes such as proteins and nucleic acids that would normally be degraded by their target cells. After demonstrating the potential of CtxB-functionalized nanoparticles for targeted subcellular delivery, we used this approach to develop a hollow mesoporous silica material amenable to intracellular protein delivery. The efficacy of this system was then demonstrated by using it to deliver a location specific cytotoxic protein.

Cholera toxin subunit B-modified mesoporous silica nanoparticles as vehicles for the improved intracellular delivery of proteins

249th National Meeting (2015)

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