(731f) Enhancing Electroporation Transfection with AuNP Polyplex

Gene delivery to mammalian cells relies on either viral infection or nonviral membrane perturbation (including chemical or physical approaches). Non-viral methods have been explored as replacements of viral systems for their low toxicity and immunogenicity. In nonviral systems, chemical methods involve the use of nanoparticles such as lipoplex and polyplex to carry therapeutic materials and facilitate their delivery while physical methods such as biolistics and electroporation, relies on also applied for gene delivery recently. Great improvements have been achieved over the years. However, they have yet to reach levels competitive to their viral counterparts on the delivery efficiency, cell viability, and targeting specificity. We hypothesize that the combination of some physical and chemical methods could improve the performance of nonviral delivery systems. Our hypothesis was evaluated by using gold nanoparticles conjugated polyplex (a chemical approach) to enhance DNA delivery by electroporation (a physical approach). Gold nanoparticles (AuNPs) of various sizes and geometries were conjugated with polyethylenimine (PEI)-plasmid polyplex under various N/P ratios. The conjugated nanoparticles were then mixed with cells and electroporated using a commercial instrument. The delivery efficiency was evaluated with both model anchor cells (i.e., NIH 3T3) and suspension cells (i.e., K562), together with their impact on cell viability. We found that AuNP polyplex showed significant enhancement on transfection efficiency. No significant increase of toxicity was found. Such a combination of physical and chemical delivery concept may stimulate further exploration in the delivery of various therapeutic materials for both in vitro and in vivo applications.