Conjugation of prostate cancer-specific aptamer to polyethylene glycol-grafted polyethylenimine for enhanced gene delivery to prostate cancer cells

Abstract

Prostate cancer is one of the most frequently diagnosed cancers in men. To enhance the tumor therapeutic efficiency and reduce undesirable side effects, there is a need for developing improved curative options. Aptamer is one of the promising targeting ligands for cancer therapy due to their high affinity to target cells. The high affinity and specificity of aptamers have attracted immense attention because of low toxicity, high stability and easy synthesis. In this study, a prostate cancer-specific aptamer Wy5a was conjugated to polyethylenimine (PEI) with a polyethylene glycol (PEG) linker for prostate cancer-specific gene delivery. PEI-PEG-AS1411 was synthesized as a non-specific control. PEI-PEG-Wy5a formed stable complexes with plasmid DNA in a spherical form with a diameter of 70 nm and positive surface-charge. In transfection assays, PEI-PEG-Wy5a had higher gene delivery efficiency to PC3 prostate cancer cells than PEI-PEG or PEI-PEG-AS1411, but not in other types of cells. Flow cytometry and confocal laser scanning microscopy results also demonstrated that PEI-PEG-Wy5a could be internalized to PC-3 prostate cancer cells efficiently. Furthermore, PEI-PEG-Wy5a showed enhanced apoptotic effects when delivered with therapeutic gene pHSV-TK. Those results suggest that PEI-PEG-Wy5a may be useful for prostate cancer-specific gene delivery.