载雄激素受体三螺旋形成寡核苷酸PEG-PLGA纳米粒子的制备与应用

Preparation and Primary Application of Androgen Receptor Triplex-forming Oligonucleotides Loaded PEG-PLGA Nanoparticles

【目的】以生物可降解材料聚乙二醇-聚乳酸聚乙醇酸共聚物(PEG-PLGA)制备载雄激素受体三螺旋形成寡核苷酸的纳米粒子(TFO-NPs),并初步探讨其对前列腺癌LNCaP细胞的生长抑制作用。【方法】采用改良自乳化溶剂挥发法(modified-SESD)制备TFO-NPs,对其形态、包封率、载药量及体外释放特点进行鉴定。倒置荧光显微镜观察LNCaP细胞对TFO-NPs的摄取情况,四唑盐(MTT)法测定体外细胞毒作用。【结果】制备的TFO-NPs呈球形、大小均匀,平均粒径128nm,平均包封率和载药量分别为72.28%和1.02%,在体外具有缓释作用。LNCaP细胞对TFO-NPs的摄取率显著高于裸TFO。TFO-NPs对LNCaP细胞的抑制作用明显强于裸TFO(P<0.05),抑制率分别为61.2%±6.5%和20.7%±3.1%。【结论】本法制备的TFO-NPs理化性质优良,在体外能够有效抑制LNCaP细胞的增殖。

[Objective] To prepare androgen receptor gene TFO loaded nanoparticles （TFO-NPs） with biodegradable material poly （ethylene glycol）-poly （lactide-co-glycolide） （PEG-PLGA） and to investigate their inhibitory effect on LNCaP cells in vitro. [Methods] TFO-NPs were prepared by modified spontaneous emulsion solvent diffusion method （modified-SESD）. Then their morphology, encapsulation rate, drug loading efficiency and drug released characteristics were identified. The uptake of TFO-NPs by LNCaP cells was observed by an inverted florescent microscope, and the cytotoxicity to LNCaP cells was determined by MTT assay. [Results] The TFO-NPs were spherical, uniform, with mean diameter of 128 nm. Their encapsulation rate and drug loading efficiency of TFO- NPs were 72.28% and 1.02%, respectively. The release test in vitro showed significant sustained release. The cellular uptake rate of TFO-NPs was markedly higher than that of naked TFO. The inhibitory effect on LNCaP cells of TFO-NPs was significantly obvious than that of naked TFO（P 〈 0.05）, and their inhibitory rates were 61.2% ± 6.5% and 20.7% ± 3.1%, respectively. [Conclusions] The physicochemical properties of TFO-NPs prepared by modified-SESD method are excellent. TFO-NPs can inhibit LNCaP cells proliferation efficiently in vitro.