Hydrolytic surface erosion of mesoporous silica nanoparticles for efficient intracellular delivery of cytochrome c

Delivery of apoptosis-associated proteins is an attractive approach to treat cancer, but their large molecular sizes and membrane-impermeability require the use of a suitable delivery carrier. As a versatile drug carrier, mesoporous silica nanoparticles (MSNs) have been utilized to transport a variety of therapeutic molecules. However, the use of MSNs for protein delivery has been limited because their conventionally obtainable pore size (ca. 2–3 nm in diameter) is too small to load large-sized biomolecular cargos. In this article, we present surface erosion of MSNs by hydrolytic degradation as a new strategy to obtain a mesoporous colloidal carrier for effective delivery of a bulky apoptosis-inducible protein, cytochrome c (CYT). A series of physicochemical properties of particles were analyzed before and after the hydrolytic surface erosion of pristine small-pored MSNs and the subsequent CYT loading. The results showed that hydrolytic degradation of MSNs imparts beneficial structural features for CYT loading and release, i.e., enlarged pores (up to ~10 nm in diameter) and roughened surface texture, leading to significantly enhanced intracellular delivery of CYT over conventional small-pored MSNs. The present results may offer a useful insight into silica degradability for tuning the internal/external surface characteristics of MSN-based colloidal particles to open a wide range of biomedical applications.