Enhanced anticancer activity of siRNA and drug codelivered by anionic biopolymer: overcoming electrostatic repulsion.

Lipika Ray, Sutapa Ray

Nanomedicine (London, England) 2023 May

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Aim: To codeliver an anticancer drug (doxorubicin) and siRNA in the form of nanoparticles into CD44-overexpressing colon cancer cells (HT-29) using an anionic, amphiphilic biopolymer comprising modified hyaluronic acid (6-O-[3-hexadecyloxy-2-hydroxypropyl]-hyaluronic acid). Materials & methods: Characterization of nanoparticles was performed using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, molecular docking, in vitro drug release and gel mobility assays. Detailed in vitro experiments, including a gene silencing study and western blot, were also performed. Results: A 69% knockdown of the target gene was observed, and western blot showed 5.7-fold downregulation of the target protein. The repulsive forces between siRNA and 6-O-(3-hexadecyloxy-2-hydroxypropyl)-hyaluronic acid were overcome by hydrogen bonding and hydrophobic interactions. Conclusion: The authors successfully codelivered a drug and siRNA by anionic vector.

Citation

Lipika Ray, Sutapa Ray. Enhanced anticancer activity of siRNA and drug codelivered by anionic biopolymer: overcoming electrostatic repulsion. Nanomedicine (London, England). 2023 May;18(11):855-874