142. Functionalized Selenium Nanoparticles for mRNA Delivery

The use of inorganic nanoparticles as gene and drug delivery agents has raised expectations in cancer treatment and diagnostics, and is considered as a promising research orientation for oncotherapy. Selenium, an essential trace element plays a fundamental role in cell metabolism, being responsible for the functioning of many enzymes and other proteins, and is also known for its chemopreventative and chemotherapeutic activities. However, its use as a gene delivery vehicle remains largely unexplored. In this study, chitosan, a positively charged natural polysaccharide was grafted onto selenium nanoparticles. Functionalized and non-functionalized SeNPs were synthesized and characterized using Transmission and Scanning Electron Microscopy, UV spectroscopy, IR spectroscopy and Nanoparticle Tracking Analysis. This study demonstrates that the coating of SeNPs with chitosan influences nanoparticle size, distribution and charge. Gel retardation and enzyme protection studies confirmed that these chitosan functionalized SeNPs were capable of binding, condensing and protecting the mRNA luc from degradation. Evaluation of the effects of functionalized and non-functionalized SeNPs on the cell viability of the human colon adenocarcinoma (HT-29) cancer cell line and Human Embryonic Kidney (HEK293) non-cancer cell line was studied using the MTT cell viability assay. SeNPs at concentrations of up to 200 µg mL−1, demonstrated low toxicity to both cell lines with percentage cell survival over 70 %. Complexes of NP: mRNA at different weight ratios (w/w) similarly exhibited low toxicity levels to both cell lines. Transfection studies were accomplished using the luciferase reporter gene assay. Results showed that the functionalized SeNPs (FSeNPs) produced greater transgene activity than the cationic polymer/mRNA complexes on their own. The results of this study suggest that FSeNP's low cytotoxicity coupled with their small particle size and surface properties, make them suitable non-viral gene delivery vectors. However further engineering and modifications of the FSeNPs may be required to enable in vivo gene delivery. The use of SeNPs has opened a new direction for synergistic treatment of cancer with higher efficiency and reduced side effects.