A Multifunctional Aptamer Decorated Lipid Nanoparticles for the Delivery of EpCAM‐targeted CRISPR/Cas9 Plasmid for Efficacious In Vivo Tumor Regression

Abstract

AbstractEpithelial cell adhesion molecule (EpCAM) gene encodes a type‐I trans‐membrane glycoprotein that is overexpressed in many cancerous epithelial cells and promotes tumor progression by regulating the expression of several oncogenes like c‐myc and other cyclins. Because of this tumorigenic association, the EpCAM gene has been a potential target for anti‐cancer therapy in recent days. Herein, it is attempted to knockout the proto‐oncogenic EpCAM expression by efficiently delivering an all‐in‐one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) plasmid via a lipid nanoparticle system made out of synthetic stimuli‐sensitive lipids. The plasmid possesses the necessary information in the form of a guide RNA targeted to the EpCAM gene. The aptamer decorated system selectively targets EpCAM overexpressed cells and efficiently inhibits the genetic expression. It has explored the pH‐responsive property of the developed lipid nanoparticles and monitored their efficacy in various cancer cell lines of different origins with elevated EpCAM levels. The phenomenon has further been validated in vivo in non‐immunocompromised mouse tumor models. Overall, the newly developed aptamer decorated lipid nanoparticle system has been proven to be efficacious for the delivery of EpCAM‐targeted CRISPR/Cas9 plasmid.