Co-delivery of AKT3 siRNA and PTEN Plasmid by Antioxidant Nanoliposomes for Enhanced Antiproliferation of Prostate Cancer Cells.

Abstract

Globally, prostate cancer is the fifth major cancer type and the second leading cause of cancer-related death in men. In 2018, about 1.3 million prostate cancer cases were reported worldwide. It is reported that loss of PTEN (tumor suppressor gene) expression leads to hyperactivation of the PI3K/AKT pathway and thus induces uncontrolled cell proliferation. Loss or mutation in regular PTEN expression is reported to occur in ∼30% of primary prostate cancer cases and ∼65% of metastatic cancer cases. Restoring the PTEN expression could inhibit the PI3K/AKT/mTOR signaling pathway, thus avoid the growth of prostate cancer cells. In this work, we have synthesized a multifunctional nanoliposomal formulation incorporating PTEN plasmid, AKT3 siRNA, and antioxidant cerium oxide nanoparticles (CeNPs). The nanoliposomes were able to successfully internalize in prostate cancer (PC-3) cells, restore the expression of PTEN protein, and knock down AKT3 mRNA. Further, the multifunctional nanoliposomes induce DNA damage and apoptosis in prostate cancer cells. The investigation of the PI3K/AKT/mTOR signaling pathway revealed that PTEN protein and apoptosis-specific proteins are overexpressed, leading to the inhibition of oncoproteins and, thus, prostate cancer.