Investigating the interaction between miRNA-loaded fluorinated dendriplexes and model floating lipid bilayers

Gene therapy offers potential treatment for diseases such as cancer and neurological disorders by altering defective genes. However, due to the instability of nucleic acids, gene delivery requires vectors. While viral vectors are effective, concerns over their safety have led to growing interest in non-viral alternatives. Among non-viral vectors, dendrimers attract attention due to their defined structure and customizable surfaces.
To enhance their performance, researchers have attached short linear fluorinated chains to dendrimers, improving serum stability, cellular uptake, endosomal escape, and reducing toxicity. Among dendrimers, those made from Bis-MPA monomers are especially promising because of their low toxicity, biodegradability, and effective gene binding. In this study, we combined Bis-MPA dendrimers with a fluorinated unit containing perfluoro-t-butoxyl groups. This design offers better biodistribution and sustainability compared to longer linear fluorinated chains. These dendrimers have four primary ammonium groups to bind with nucleic acids. A key limitation of current delivery systems, like lipid nanoparticles, is inefficient endosomal escape. However, fluorinated polymers have recently shown the ability to significantly boost uptake and escape by 3-10 times, although the exact mechanism remains unclear. Hence, we aim to investigate the interaction between these dendriplexes and floating lipid bilayers to improve gene delivery effectiveness.