Synthesis of guanidinium‐dendrimer‐type pDNA carriers for gene delivery into floating blood cells

Abstract

Guanidinium‐dendrimer‐type pDNA carriers have been synthesized for gene delivery into floating blood cells. A 2nd generation polyamidoamine (PAMAM‐G2) dendrimers were modified with guanidinium groups at the primary amine. The resulting PAMAM‐G2‐Gu dendrimer with a modification degree of 53 mol%, PAMAM‐G2‐Gu(53), formed polyion complexes (PICs) above a mixing positive/negative charge ratio (+/−) of 64. The resulting PAMAM‐G2‐Gu(53)/pDNA PIC was stable for 24 h in the presence of 10% fetal bovine serum and exhibited no significant cytotoxicity against HL‐60 human leukemia cells during the above incubation. It is worth noting that the PAMAM‐G2‐Gu(53)/pDNA PIC at mixing positive/negative (+/−) charge ratio of 64 mediated the highest gene expression among all PICs in this study such as an unmodified PAMAM‐G2, the PAMAM‐G2 modified with diethylaminoethyl groups (PAMAM‐G2‐DEAE). Especially, the resulting gene expression was higher than commercially available branched poly(ethylenimine) (b‐PEI). Consequently, the PAMAM‐G2‐Gu(53)/pDNA PIC is effective for gene delivery to floating blood cells and is expected to be applied to ex vivo transfection.