Guanidinylated bioresponsive poly(amido amine)s designed for intranuclear gene delivery

Abstract

Guanidinylated poly(amido amine)s with multiple disulfide linkages (Gua-SS-PAAs) were designed and constructed as nonviral gene carriers. The main chains of these novel carriers were synthesized based on monomers containing guanidino groups (guanidine hydrochloride and chlorhexidine), which could avoid complicated side-chain-modification reactions while introducing the guanidino groups. The synthesized Gua-SS-PAAs polymers were characterized by 1 H nuclear magnetic resonance, molecular weight, and polydispersity. Furthermore, Gua-SS-PAAs polymers were complexed with p DNA, and the properties of the complexes were determined, including entrapment efficiency, particle size, ζ -potential, atomic force microscopy images, stability, DNA complexation ability, reduction sensitivity, cytotoxicity, and transfection efficiency. The new Gua-SS-PAAs carriers exhibited higher transfection efficiency and lower cytotoxicity compared with two widely used gene delivery carriers, polyethylenimine and lipofectamine 2000. Furthermore, the relationship between the side-chain structure and morphological/biological properties was extrapolated, and the results showed that guanidine in the side chain aids in the improvement of transfection efficiency. In addition, the introduction of guanidino group might confer the new carriers with nuclear localization function compared to carriers without it.

Thiol Michael addition reaction: a facile tool for introducing peptides into polymer‐based gene delivery systems

“…Cationic polymers are one of the main categories of non‐viral vectors, having attracted increasing attention due to their inherent advantages, including non‐immunogenicity, better stability, larger gene capacity and ease of preparation , . Various cationic polymers such as polyethyleneimine (PEI), poly( l ‐lysine), polyamidoamine dendrimers, , and polyamidoamines, have been synthesized for gene delivery. However, the crucial drawbacks of these polymers are their cytotoxicity and relatively low transfection efficiency, thus great effort has been dedicated to solve this issue .…”

Guanidinylated Cyclic Synthetic Polypeptides Can Effectively Deliver siRNA by Mimicking the Biofunctions of Both Cell-Penetrating Peptides and Nuclear Localization Signal Peptides

“…More importantly, Cheng et al found that cationic synthetic polypeptides with stable α-helices can transport siRNA into targeted cells quite efficiently by mimicking the membrane activity of CPPs . Several additional studies have reported that guanidinylated polymeric vectors have nuclear localization capabilities. − However, to the best of our knowledge, synthetic polypeptides with dual functions of rapid cell-penetrating activity and fast nuclear localization have not yet been reported. More importantly, the beauty of ROP of NCAs is that it permits the preparation of several grams of polypeptides at one time and the tailor-made manipulations of the length of the backbone chain, the structure of side chains, and the properties of the polypeptides.…”