ao8b00738_si_001.pdf (571.92 kB)
Enhancing Gene-Knockdown Efficiency of Poly(N‑isopropylacrylamide) Nanogels
journal contribution
posted on 2018-07-18, 18:50 authored by Sonal Deshpande, Smita Patil, Neetu SinghPolo-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.