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Ligands with Delocalized Charge Density and Hydrophobicity Significantly Affect the Transfection Efficacy of the PAMAM Dendrimer

[ Vol. 2 , Issue. 4 ]

Author(s):

Santosh Yadav, Ayushi Priyam, Manohar Mahato, Smriti R. Deka and Ashwani K. Sharma   Pages 196 - 207 ( 12 )

Abstract:


Polyamidoamine dendrimers (PAMAM) are being used as efficient vectors for delivery of nucleic acids to the cells. However, these dendrimers cause a significant amount of cytotoxicity. In order to improve its transfection efficiency and cell viability, surface amine groups of PAMAM were converted into guanidinium (Gn) and tetramethylguanidinium (TMG) moieties. These modified PAMAM dendrimers interacted with negatively charged plasmid DNA efficiently and formed stable complexes as revealed by dynamic light scattering analysis. PAMAM/pDNA, PAMAM-TMG/pDNA and PAMAM-Gn/pDNA complexes were found to be in the range of 175-250 nm with zeta potential in the range of +21-37 mV. Further, these modified dendrimers did not display toxicity rather it decreased a bit when tested in HEK293, HeLa and MCF-7 cells. Among these modified dendrimers, PAMAM-Gn/pDNA complex displayed the highest transfection efficiency in both the cell lines HEK293 and MCF-7.

Keywords:

Cytotoxicity, dendrimer, gene delivery, PAMAM, transfection.

Affiliation:

Nucleic Acids Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110 007, India.



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