DEVELOPMENT OF TARGETED MESOPOROUS SILICA SUPPORTED LIPID BILAYER NANOPARTICLES FOR DELIVERY OF NUCLEIC ACID CARGO
Ayse Muniz1, Amanda Lokke1, Paul Durfee1, Kimberly Butler1, Jason Townson2, Yu-Shen Lin2, Jeffrey Brinker1,3.
1The University of New Mexico, Albuquerque, NM, 2Oncothyreon Incorporated, Seattle, WA, 3Sandia National Laboratories, Albuquerque, NM.
Gene therapy remains a promising approach for treatment of a diverse range of diseases. However, providing reliable, cell-specific delivery of nucleic acids to cells in vivo remains a significant challenge. Improvement of delivery efficacy likely requires greater control over cargo stability, cellular specificity, gene integration, and expression. Current non-viral methods of in vivo nucleic acid delivery in mice such as cationic liposomes, polymers, peptides, or other nanoparticle-based complexes, have emerged as safer and cheaper alternatives to their viral counterparts. However, maximizing efficiency and specificity while minimizing toxicity using these methods is currently limited. Mesoporous silica nanoparticles (MSNPs) serve as an attractive option for targeted interaction with cells due to their ability to undergo surface modification while maintaining stability. We have modified MSNPs with 8 nm pore sizes to efficiently encapsulate and deliver nucleic acid cargos including DNA, siRNA, and mRNA to HeLa cells in vitro and highly vascularized chicken embryo models in vivo. Variables including nanoparticle shape, charge and size, and various liposomal formulations were explored to understand their effects on nucleic acid delivery. We demonstrate in vitro plasmid transfection efficiencies greater than 80% after 48 hours, greater than 95% efficiency for mRNA delivery, and 50% gene knockdown with siRNA delivery using our MSNP platform. It remains the goal of this research to modify MSNPs to deliver nucleic acids to targeted cells with high efficiency in vivo. By developing a universal nucleic acid carrier, current delivery methods could be dramatically improved to achieve higher specificity and lower toxicity.