Capsid-like biodegradable poly-glycolic acid nanoparticles for a long-time release of nucleic acid molecules

Gene therapy can be described as the direct transfer of genetic material to cells or tissue for thetreatment of inherited and acquired diseases. Viral vectors have long been proven to be the mostefficient and stable vectors for transgene delivery into the cell, but they still have some safety issues.Non-viral nanosystems can overcome these safety problems and limitations of viral vectors. FDAapprovedpolymers are particularly attractive for gene delivery applications. Here, sustained release ofplasmid DNA encoding the EGFP protein, used as a model, showed efficient delivery through newcapsid-like biodegradable polyglycolic acid (PGA) nanoparticles (NPs). PGA NPs showed a mean size of135 nm, with a polyhedron structure. Prior to loading into the PGA NPs, the pT7-EGFP plasmid wascomplexed with pH- and enzyme-responsive polycation polymers in order to guarantee high loading,stability, and controlled plasmid release over time. Our PGA NPs are hemocompatible, non-cytotoxicand have the ability to protect the gene cargo from DNase and serum action. Further, our PGA NPsexhibited a controlled and sustained transfection of cells that grow in suspension (human Tlymphocytes, Jurkat) and adherent cell lines (human neuroblastoma cells, SH-SY5Y, and human cervixcarcinoma cells, HeLa), with respect to transfection with commercial Lipofectamine 3000. In addition,our PGA NPs showed the ability to penetrate into 3D neurospheres, allowing transfection of inner cells.Our capsid-like NPs, thanks to their properties of biocompatibility, biodegradability, hemocompatibility,and sustained plasmid release, can be used as an efficient tool for transfection to overcome theproblems of viral vectors.