Nanoparticle delivery of siRNAs in epithelial ovarian cancer treatment

Epithelial ovarian cancer (EOC) is the most fatal gynaecological cancer with a 5-year survival rate of only 46% [1]. Since most symptoms in the initial stage of EOC are uncertain and effective early detection techniques have not been developed, approximately 75% of EOC cases are diagnosed at an advanced stage [2]. The fast-spreading metastatic cancer cells require urgent and effective therapy, but the current treatments such as chemotherapy, radiation, and surgery are not efficacious enough to cure EOC completely. Surgical debulking of ovarian tumours followed by paclitaxel and platinum-based chemotherapy is considered as a standard therapy, but this still results in recurrence in the majority of cases [3]. Oligonucleotide-based therapy employing RNA interference (RNAi) holds great promise as a therapy for metastatic EOC. During RNAi processes, microRNAs (miRNAs) or small interfering RNAs (siRNAs) can bind to messenger RNAs (mRNAs) with complementary sequences and then neutralize the binding mRNAs, leading to prevention of the gene expression. SiRNA molecules are double-stranded oligonucleotides with 20 to 25 base pairs in length, and upon cellular entry they split into single-stranded RNAs, which further guide a ribonucleoprotein, RNA-induced silencing complex (RISC), to degrade the complementary mRNAs. The efficient gene-silencing potential of siRNAs provides an option to treat many diseases which are caused by the unusual expression of single or multiple genes [4].