Enhancing Gene-Knockdown Efficiency of Poly(N‑isopropylacrylamide) Nanogels

Polo-like-kinase 1 (PLK1), which is a serine–threonine protein kinase overexpressed in cancer cells, is known to regulate tumor growth and have recently gathered attention as a target gene for RNA interference because of the poor bioavailability and nonspecificity of the available inhibitors. However, the lower transfection efficiency of siRNA and its poor stability in biological mileu necessitate the need of efficient siRNA delivery systems. Here, we report efficacious polymeric nanoparticles for the delivery of PLK1 siRNA in mammalian cancer cells. N-Isopropylacrylamide (NIPAm) and N-isopropylmethacrylamide-co-NIPAm nanogels were synthesized and modified using poly-ε-lysine. Furthermore, their ability to induce gene silencing was investigated by flow cytometry and real-time polymerase chain reaction, and the silencing efficiency observed was related to the polymer composition and its effect on the gene loading and protection ability and the endosomal escape capability. This study attempts to leverage the understanding of the cell–material interaction, thus, addressing the bottlenecks of siRNA delivery for enhancing the efficacy of the poly­(N-isopropylacrylamide)-based delivery vehicle.