Effect of lipid nanoparticle siRNA delivery systems on silencing clusterin and progression in enzalutamide resistant prostate cancer in vivo.

256 Background: Clusterin (CLU) is induced by androgen receptor (AR) pathway inhibition and its overexpression confers treatment resistance. Lipid nanoparticle (LNP) facilitates tumor uptake and intracellular processing through an enhanced permeation and retention effect (EPR), currently with multiple products undergoing clinical evaluation. Gene silencing using small interfering RNA (siRNA) is a promising approach but in vivo delivery remains a major barrier. In our study, we investigated the efficacy siRNA tumor delivery using LNP systems in enzalutamide-resistant (ENZ-R) castration-resistant prostate cancer (CRPC) model. Methods: To validate the effect of LNP siRNA tumor delivery in vivo, gene silencing of a reporter gene, luciferase (LUC), in PC3-M-luc stable cell line was treated with LNP LUC-siRNA and examined for Luc activity by the IVIS imaging system. Next, we investigated the efficacy of LNP CLU-siRNA tumor delivery and LNP CLU-siRNA sensitized AR knockdown activity in ENZ-R CRPC LNCaP in vitro ...