Anisamido-Polyethylenimines as Efficient Nonviral Vectors for the Transport of Plasmid DNA to Sigma Receptor-Bearing Cells In Vitro.

Site-specific delivery of therapeutics promises better outcomes in the treatment of diseases. A small ligand, anisamide, has been shown to specifically bind sigma receptors highly overexpressed on prostate cancer cells, one of the leading cancers causing deaths worldwide. Here, anisamide-tethered polyethylenimine polymers (AP) have been synthesized and evaluated for their capability to transport nucleic acid across the cell membrane. A series of modified polymers (AP-1 to AP-4) was synthesized, physicochemically characterized, and evaluated for their transfection efficiency and cytotoxicity. Postconjugation, there was a marginal decrease in the buffering capacity; however, it did not diminish the ultimate objective of the study rather improved the transfection efficiency and decreased the cytotoxicity making these polymers as efficient and safe vectors for nucleic acid delivery. All the modified polymers displayed enhanced capability to deliver DNA inside the cells. Among the series, the modified polymer, AP-4 (10% attempted substitution), exhibited the highest transfection in HEK293 cells having abundant sigma receptors with minimal cytotoxicity. The projected polymer also showed complete protection of bound DNA against enzymatic degradation. Altogether, the results demonstrated targeting ability of the proposed polymers to deliver nucleic acid to sigma receptor-bearing cells in vitro.