Silicon nanomaterials provide an excellent platform for the development of new biologically active agents because of their stability, ease of chemical modification, and their biocompatibility. One such field of study is the use of silicon nanoparticles (SiNPs) as potential delivery vehicles for therapeutic agents. Untargeted SiNPs have already been shown to preferentially concentrate within blood vessels of tumors in vivo. However, with the addition of targeting ligands, these nanoparticles could be directed to sites within the body that are traditionally difficult to deliver therapeutics to, such as the brain, owing to the difficulty of crossing the blood brain barrier (BBB). One potential ligand we have been investigating is a metalloprotease isolated from the fungus Cryptococcus neoformans.            C. neoformans is a fungal pathogen that infects individuals with compromised immune systems, where it gets into the bloodstream, and invades the brain by, crossing the BBB. We have identified and isolated a metalloprotease (Mpr1) in this fungus, that when knocked out, results in reduced crossing of the BBBin both in vitro and in vivo models. In addition, expressing Mpr1 in an unrelated fungus, the baker's yeast Saccharomyces cerevisiae, confers the same crossing ability to this non-pathogenic yeast.            A collaboration with the Kauzlarich research group has resulted in the development of a brain-specific drug delivery platform that couples SiNP with Mpr1. We have synthesized Mpr1-SiNP nanocarriers, and determined that  both the fluorescence properties of the SiNPs and the biochemical properties of the Mpr1 are retained.

Coupling a fungal secreted ligand and silicon nanoparticles for the development of brain specific drug delivery platform

248th National Meeting (2014)

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