Preparation Of Gene Vectors Based On Au Nanoparticles

Gene therapy demonstrates great potential to cure cancer and genetic disorders while the development of efficient and safe gene vectors is gene vector is still the main challenge of gene therapy. In comparison with other gene vectors, cationic gene vectors show low host immunogenicity and can be produced on a large scale, and received increasing attention for their potential applications in gene therapy. Due to good biocompatibility, low cytotoxicity and unique physical and chemical properties, Au nanoparticles (Au NPs)-based materials have been widely used in biomedicine. Recently, Au NPs-based gene vectors with high transfection efficiency and low cytotoxicity become pursuing target.A facile strategy to combine the advantages of gold nanorods (Au NRs) and polycations through surface functionalization was developed. Different Au NR carriers with a controlled amount of poly(2-(N,N-dimethyl amino)ethyl methacrylate) (PDMAEMA) brushes could be readily synthesized via surface-initiated atom transfer radical polymerization to achieve optimized nanohybrids for gene transfection. The obtained gene carriers demonstrate much higher gene transfection efficiency and lower cytotoxicity compared with polyethylenimine (25 kDa, gold standard of nonviral gene vector) in both COS7 and HepG2 cell lines. In addition, the potential of the PDMAEMA-grafted Au NR carriers to be utilized as a computed tomography contrast agent for the imaging of cancer cells has also been investigated. This strategy may realize the gene therapy and real-time imaging within one nanostructure and facilitate biomedical applications.There is now ample evidence that physicochemical properties, such as size, shape, and surface chemistry, can dramatically influence the behaviors of Au NPs in biological systems and the investigation on these parameters could be fundamentally helpful for their applications as gene carriers. In this work, we designed a series of novel gene carriers employing polycation modified Au NPs with five different morphologies while keeping uniform surface functionality. Then the effects of particle size and shape of these five different carriers on gene transfection were investigated. The morphology of Au NPs is demonstrated to play an important role in gene transfection. Arrow headed Au nanorods (Au AHNRs) were found to fabricate the most efficient gene carriers with compromised cytotoxicity. These results may provide new avenues to develop promising gene carriers and useful information for the interaction of Au NPs with biological systems.