Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines / 药学实践杂志

ABSTRACT

Objective To construct a gene delivery carrier with aptamer-polyethylene glycol-dendrimer-polyamidoamine (APT-PEG-PAMAM) ,forming nanoparticles to specifically target prostate cancer cell lines ,carrying prostate cancer cell pro-liferative suppressor microRNAmiRNA-34a .We investigated the transfection efficiency of this gene delivery system as well as functionally studied its inhibitory effect on prostate cancer (PCa) cell proliferation .Methods The construction of APT-PEG-PAMAM gene carrier was identified and confirmed by nuclear magnetic resonance (NMR) .The nano-complex sizes and zeta potential of APT-PEG-PAMAM gene carrier complexes were measured by zeta sizer .The efficiency of gene transfection of APT-PEG-PAMAM /miRNA nano-complexes were investigated by measuring the expression miRNA-34a in prostate cancer cells (PC3 and LNCaP);the PCa specific cell proliferation inhibition of APT-PEG-PAMAM / miRNA-34a nano-complexes were investigated by measuring CCK-8 cell proliferation inhibition experiments by comparing with APT-PEG-PAMAM and APT-PEG-PAMAM /miRNA-34a nano-complexes .Results NMR results demonstrated that APT-PEG-PAMAM /miRNA-34a nano-complexes were successfully synthesized by structural identification .Qualitative and quantitative transfection efficien-cy experiments data show that the cellular uptake of vectors were concentration-dependent ,after the APT further modified it significantly and increased the LNCaP cell transfection efficiency and specificity of PCa cells targeting ability .CCK8 cell prolif-eration assay data indicated that APT-PEG-PAMAM/miRNA-34a has the anti-PCa cells effect .Conclusion APT-PEG-PAM-AM/miRNA-34a may prove to see its efficacy for near future in pre-clinical and clinical study on the treatment of PCa .