Nabil A Alhakamy1, Cory J Berkland. 1. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Abstract
Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression but poses a risk of increased cytotoxicity and immunogenicity compared to low molecular weight CCPs. Conversely, low molecular weight CPPs typically have low transfection efficiency due to large complex size. Complexes made using low molecular weight CPPs were found to be condensed to a small size by adding calcium. In this study, complexes of low molecular weight polyarginine and pDNA were condensed with calcium. These complexes showed high transfection efficiency and low cytotoxicity in A549 carcinomic human alveolar basal epithelial cells. The relationships between transfection efficiency and polyarginine size (5, 7, 9, or 11 amino acids), polyarginine/pDNA charge ratios, and calcium concentrations were studied. Polyarginine 7 was significantly more effective than other polyarginines under most formulation conditions, suggesting a link between cell penetration ability and transfection efficiency.
Cell penetrating peptides (CPPs) have been extensively studied in n class="Chemical">polyelectrolyte complexes as a means to enpan>hance the transfection efficienpan>cy of plasmid DNA (pDNA). Inpan>creasing the molecular weight of CPPs oftenpan> enpan>hances genpan>e expression but poses a risk of increased n class="Disease">cytotoxicity and immunogenicity compared to low molecular weight CCPs. Conversely, low molecular weight CPPs typically have low transfection efficiency due to large complex size. Complexes made using low molecular weight CPPs were found to be condensed to a small size by adding calcium. In this study, complexes of low molecular weight polyarginine and pDNA were condensed with calcium. These complexes showed high transfection efficiency and low cytotoxicity in A549 carcinomic human alveolar basal epithelial cells. The relationships between transfection efficiency and polyarginine size (5, 7, 9, or 11 amino acids), polyarginine/pDNA charge ratios, and calcium concentrations were studied. Polyarginine 7 was significantly more effective than other polyarginines under most formulation conditions, suggesting a link between cell penetration ability and transfection efficiency.
Authors: Seungbin Cha; Sun Hwa Lee; Sung Hun Kang; Mohammad Nazmul Hasan; Young Jun Kim; Sungpil Cho; Yong-Kyu Lee Journal: Biomater Res Date: 2018-07-27