School of Pharmacy, University of Queensland, Brisbane, Australia.
Nanomedicine. 2010 Jun;6(3):463-70. doi: 10.1016/j.nano.2009.12.001. Epub 2010 Jan 4.
Although small interfering RNA (siRNA) treatment holds great promise for the treatment of cancers, the field has been held back by the availability of suitable delivery vehicles. For cervical cancer the E6 and E7 oncogenes are ideal siRNA targets for treatment. The purpose of the present study was to explore the potential of dendrosomes for the delivery of siRNA targeting E6 and E7 proteins of cervical cancer cells in vitro. Optimization of dendrimer generation and nitrogen-to-phosphate (N/P) ratio was carried out using dendrimer-fluorescein isothiocyanate oligo complexes. The optimized N/P ratios were used in formulating complexes between dendrimers and siRNA targeting green fluorescence protein (siGFP). Although formulation 4D100 (dendrimer-siRNA complex) displayed the highest GFP knockdown, it was also found to be highly toxic to cells. In the final formulation 4D100 was encapsulated into dendrosomes so as to mask these toxic effects. The optimized dendrosomal formulation (DF), DF3 was found to possess a siGFP-entrapment efficiency of 49.76% +/- 1.62%, vesicle size of 154 +/- 1.73 nm, and zeta potential of +3.21 +/- 0.07 mV. The GFP knockdown efficiency of DF3 (dendrosome) was found to be almost identical to that of 4D100, but the former was completely nontoxic to the cells. DF3 containing siRNA against E6 and E7 was found to knock down the target genes considerably, as compared with the other formulations tested. Our results imply that dendrosomes hold potential for the delivery of siRNA and that a suitable targeting strategy could be useful for applications in vivo.
siRNA treatment holds great promise for the treatment of cancers, but overall, the availability of suitable delivery vehicles remains a major issue. The purpose of this study was to explore the potential of dendrosomes for the delivery of siRNA targeting specific proteins in cervical cancer cells in vitro. The results suggest that dendrosomes hold potential for the delivery of siRNA and a suitable targeting strategy could be useful for applications in vivo.
虽然小干扰 RNA（siRNA）治疗在癌症治疗方面有很大的前景，但由于缺乏合适的输送载体，该领域一直受到限制。对于宫颈癌，E6 和 E7 癌基因是治疗的理想 siRNA 靶点。本研究的目的是探讨树状大分子用于体外递送达宫颈癌细胞中 E6 和 E7 蛋白靶向 siRNA 的潜力。使用树枝状大分子-荧光素异硫氰酸酯寡聚物复合物优化树枝状大分子的生成和氮-磷（N/P）比。优化的 N/P 比用于形成针对绿色荧光蛋白（siGFP）的树枝状大分子和 siRNA 的复合物。虽然配方 4D100（树枝状大分子-siRNA 复合物）显示出最高的 GFP 敲低，但它也被发现对细胞有很高的毒性。在最终的配方中，4D100 被封装到树突中，以掩盖这些毒性作用。优化的树突状配方（DF），DF3 被发现具有 49.76%+/-1.62%的 siGFP 包封效率，154+/-1.73nm 的囊泡大小，和+3.21+/-0.07mV 的 ζ 电位。DF3（树突）的 GFP 敲低效率与 4D100 几乎相同，但前者对细胞完全无毒。与测试的其他配方相比，DF3 中含有针对 E6 和 E7 的 siRNA 可显著敲低靶基因。我们的结果表明，树突状大分子具有递送 siRNA 的潜力，并且合适的靶向策略对于体内应用可能是有用的。
siRNA 治疗在癌症治疗方面有很大的前景，但总的来说，合适的输送载体的可用性仍然是一个主要问题。本研究的目的是探讨树突状大分子用于体外递送达宫颈癌细胞中特定蛋白质靶向 siRNA 的潜力。结果表明，树突状大分子具有递送 siRNA 的潜力，合适的靶向策略对于体内应用可能是有用的。
