Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells

Abstract

We have previously described the development of novel sterically stabilized F3-targeted pH-sensitive liposomes, which exhibited the ability to target both cancer and endothelial cells. Herein, the therapeutic potential of those liposomes was assessed upon encapsulation of a siRNA against a well-validated molecular target, PLK1. Treatment of prostate cancer (PC3) and angiogenic endothelial (HMEC-1) cells with F3-targeted liposomes containing anti-PLK1 siRNA resulted in a significant decrease in cell viability, which was mediated by a marked PLK1 silencing, both at the mRNA and protein levels. Furthermore, pre-treatment of PC3 cells with F3-targeted liposomes containing anti-PLK1 siRNA enabled a 3-fold reduction of paclitaxel IC50 and a 2.5-fold augment of the percentage of cancer cells in G2/mitosis arrest, which ultimately culminated in cell death. Overall, the F3-targeted nanocarrier containing an anti-PLK1 siRNA might constitute a valuable system for prostate cancer treatment, either applied in a single schedule or combined with conventional chemotherapy.

Keywords: 1, 2-dioleoyl-3-trimethylammonium-propane; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; 1,2-distearoyl-sn-glycero-3-phosphocholine; 12-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Maleimide (Polyethylene Glycol)(2000)] ammonium salt; C(16)-Ceramide mPEG(2000); CHEM; CHOL; CTR; DOPE; DOTAP; DRI; DSPC; DSPE-PEG-MAL; G2/M phases; G2/mitosis phases; Gene silencing; HMEC-1; IC(50); N-Palmitoyl-Sphingosine-1-[Succinyl(MethoxyPolyethylene Glycol)(2000)]; Nanotechnology; PBS; PC3; PC3 prostate cancer cells; PLK1; Paclitaxel; Prostate cancer; SD; Scholesteryl hemisuccinate; cholesterol; control; dose reduction index; eGFP; enhanced Green Fluorescent Protein; half maximal death concentration; human microvascular endothelial cells; phosphate buffer saline; polo-like kinase 1; siRNA; small-interfering RNA; standard deviation.