Novel Layer-By-Layer Self-Assembled Peptide Nanocarriers For Sirna Delivery
Denkbas, Emir Baki
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All complex and functional structures of nature consist of simple building blocks that are thermodynamically balanced and self-assembled at the molecular level. Production of functional bio-nanomaterials with molecular self-assembly mechanisms, based on a bottom-up approach, has become increasingly important in recent years. In this study, a biodegradable and biocompatible siRNA nanocarrier system, consisting of diphenylalaninamide (FFA) based nanoparticles, was developed for silencing of HER2, a gene known to be overexpressed in breast cancer. FFA contains an amide functional group that has a dipolar nature with zero net charge. Here we report an original approach to functionalizing peptide nanoparticles based on layer-by-layer polyelectrolyte deposition (LbL PD) technique. The resulting well-defined FFA nanoparticles (FFANPs) were coated with polycationic poly-Llysine (PLL) by cation-dipole interaction, giving rise to a net positive surface charge. The PLL coating improved the physical stability of FFANPs at physiological pH and temperature. The cationized FFANP was then interacted with the polyanionic siRNA, forming an FFANP-PLL/siRNA complex. Nanoparticles were then interacted with PLL one more time, to create a third layer that can prevent degradation of the siRNA by nucleases and achieve effective delivery of the siRNA into the cytoplasm. These original FFANP-PLL/siRNA/PLL were optimized to achieve efficient in vitro gene silencing. Overall, this study shows that FFANP-PLL/siRNA/PLL are promising gene carriers for gene silencing therapies.