(96j) Iron Sulfide Supraparticles As Artificial Viruses for Gene and Gene Editing Therapies

Gene and gene editing therapies have been widely investigated for treatment of inherited or acquired genetic diseases. Efficient delivery of therapeutic agents has become a significant barrier in clinical applications due to the toxicity and instability of the vectors in the complex intracellular environment. Among non-viral vectors, individual inorganic nanoparticles (NPs) have become a popular strategy for nucleic acid delivery. However, the nanoshell geometry of viruses is advantageous for the gene/CRISP cargo protection. Therefore, we synthetized L-cysteine stabilized iron-based inorganic nanoparticles which self-assemble into supraparticles with nanoshell geometry. Transmission electron microscopy (TEM), TEM tomography and dynamic light scattering (DLS) were used to characterize the virus-like supraparticles size, shape, and charge. Our results indicate that virus-like supraparticles contain continuous compartments, are positively charged (25±7.2 mV) and 74±21 nm in diameter. We loaded the DNA in the compartments during the formation of supraparticles. We tested these complexes in circular dichroism, UV-Vis spectroscopy, electrophoretic mobility shift and protection assays. Since iron sulfide is a natural material, it presumably has low cytotoxicity and high biocompatibility. Supraparticles can condense DNA, protect it against degradation, penetrate through cellular membranes and facilitate endolysosomal escape in gene therapy. Therefore, development of these particles can be used as an effective cargo delivery tool for gene and gene editing therapies.