PAMAM Dendrimers Conjugated with L-Arginine and γ-Aminobutyric Acid as Novel Polymeric Gene Delivery Carriers

Abstract

In this study, we synthesized functional dendrimer derivatives as nonviral gene delivery vectors. Poly(amidoamine) dendrimer (PAMAM, generation 4) was modified to possess functional amino acids to enhance gene transfection efficiency. PAMAM G4 derivatives conjugated with L-arginine (Arg) and γ-aminobutyric acid (GABA) showed higher transfection efficiency and lower cytotoxicity compared to the native PAMAM G4 dendrimer. The polyplex of the PAMAM G4 derivative/pDNA was evaluated using an agarose gel retardation assay and Picogreen reagent assay. Additionally, the MTT assay was performed to examine the cytotoxicity of synthesized polymers. All PAMAM G4 derivatives showed lower cytotoxicity than PEI25kD. Particularly, PAMAM G4-GABA-Arg displayed enhanced transfection efficiency compared to the native PAMAM G4 dendrimer.

Surface-Engineered Dendrimers in Gene Delivery

“…Besides the charge density effect, the positive charge of the guanidinium group in arginine is delocalized on three nitrogen atoms; thus, guanidinium shows better interaction with phosphates in DNA than localized cations such as ammonium . In addition, the guanidinium group in arginine has a strong affinity for cell membranes through ionic pairing and hydrogen bonding. , On the basis of these reasons, arginine- and lysine-modified dendrimers were widely used as efficient vectors for DNA and siRNA during the past decade. ,,− The efficacy of arginine- and lysine-modified dendrimers depends much on the dendrimer species. For example, arginine-modified PAMAM dendrimers are more efficient in gene transfection than lysine-modified ones, , while lysine-modified PPI dendrimers are more efficient than arginine-modified ones. , The linkage between amino acid and dendrimer also plays a critical role in gene delivery.…”