Comparison between arginine conjugated PAMAM dendrimers with structural diversity for gene delivery systems

    loading  Checking for direct PDF access through Ovid

Abstract

Mono- and di-arginine conjugated PAMAM dendrimers (G = 3 or 4) were synthesized to examine the structure-activity relationships of arginine conjugation for gene delivery systems. Number of conjugated arginines was examined by 1H NMR (PAMAM3-R: 31, PAMAM4-R: 60, PAMAM3-R2: 59, PAMAM4-R2: 116). They could retard pDNA at a charge ratio of 2 and form polyplexes with sizes less than 250 nm from a charge ratio of 4. Di-arginine conjugated dendrimers showed higher Zeta-potential values and polyplex stabilities than mono-arginine conjugates. PAMAM3-R and PAMAM4-R showed low cytotoxicities even at high concentration but PAMAM3-R2 and PAMAM4-R2 exhibited significant cytotoxicities at high concentration. PAMAM3-R2 displayed greater transfection efficiency than PAMAM3-R, although the transfection efficiency of PAMAM4-R2 was not higher than that of PAMAM4-R in all condition. PAMAM3-R2 and PAMAM4-R2 polyplexes were observed to show the good intra-nuclear localization in comparison with PAMAM3-R and PAMAM4-R. It is concluded that di-arginine conjugation to PAMAM dendrimers can improve polyplex stability, intra-nuclear localization, and transfection efficiency but also induce charge density- and generation-dependent cytotoxicity. Therefore, a novel strategy for highly densed arginine conjugation maintaining low cytotoxicity will be needed for the development of efficient gene delivery carriers.

Graphical abstract

Comparison between arginine conjugated PAMAM dendrimers with structural diversity for gene delivery systems

Related Topics

    loading  Loading Related Articles