Yuan Xudong, Li Ling, Rathinavelu Appu, Hao Jinsong, Narasimhan Madhusudhanan, He Matthew, Heitlage Viviene, Tam Linda, Viqar Sana, Salehi Mojgan
Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 Dekalb Avenue, NY 11201, USA.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2821-8. doi: 10.1166/jnn.2006.436.
RNA interference (RNAi) is an emerging technology in which the introduction of double-stranded RNA (dsRNA) into a diverse range of organisms and cell types causes degradation of the complementary mRNA. It offers a broad spectrum of applications in both biological and medical research. Small interference RNA (siRNA) was recently explored for its therapeutical potential. However, the drug delivery of siRNA oligos is very novel and is in great need of future research. To this end, a biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle drug carrier system was prepared to load siRNA oligos with desired physicochemical properties. The nanoparticles were characterized by scanning electron microscopy and laser diffraction particle sizer. The delivery of siRNA into the targeted 293T cells was observed using fluorescent-labeled double-stranded Cy3-oligos. The model siRNA oligos, si-GFP-RNA, were also successfully loaded into PLGA nanoparticles and delivered in 293T cells. The gene silencing effect and the inhibition of GFP expression were investigated using fluorescent microscopy. Both positive and negative controls were used to compare with the new siRNA nanoparticle delivery system. It was found that nanoparticles offered both effective delivery of siRNA and prominent GFP gene silencing effect. Compared to conventional carrier systems, the new biodegradable polymeric nanoparticle system may also offer improved formulation stability, which is practically beneficial and may be used in the future clinical studies of siRNA therapeutics.
RNA干扰（RNAi）是一项新兴技术，在多种生物体和细胞类型中引入双链RNA（dsRNA）会导致互补mRNA的降解。它在生物学和医学研究中都有广泛的应用。最近对小干扰RNA（siRNA）的治疗潜力进行了探索。然而，siRNA寡核苷酸的药物递送非常新颖，急需未来的研究。为此，制备了一种可生物降解的聚（D，L-丙交酯-共-乙交酯）（PLGA）纳米颗粒药物载体系统，以负载具有所需物理化学性质的siRNA寡核苷酸。通过扫描电子显微镜和激光衍射粒度仪对纳米颗粒进行了表征。使用荧光标记的双链Cy3-寡核苷酸观察了siRNA向靶向293T细胞的递送。模型siRNA寡核苷酸si-GFP-RNA也成功负载到PLGA纳米颗粒中并递送至293T细胞中。使用荧光显微镜研究了基因沉默效果和GFP表达的抑制情况。使用阳性和阴性对照与新的siRNA纳米颗粒递送系统进行比较。发现纳米颗粒既提供了有效的siRNA递送，又具有显著的GFP基因沉默效果。与传统载体系统相比，新的可生物降解聚合物纳米颗粒系统还可能提供更好的制剂稳定性，这在实际应用中是有益的，并且可能用于未来的siRNA治疗临床研究。
