siRNA-Conjugated Nanoparticles to Treat Ovarian Cancer

Abstract

Ovarian cancer is the fifth-most lethal cancer among women due to a lack of early detection and late-stage treatment options, and it is responsible for more than 14,000 deaths each year in the United States. Recently, there have been advances in RNA interference therapy, specifically with small interfering RNA (siRNA), to reduce tumor burden for ovarian cancer via gene down-regulation. However, delivery of siRNA poses its own challenges, as siRNA is unstable in circulation, is unable to be effectively internalized by cells, and may cause toxicity in off-target sites. To address such challenges, nanoparticle carriers have emerged as delivery platforms for the biocompatible, targeted delivery of siRNAbased therapies. Several preclinical studies have shown the promising effects of siRNA therapy to reduce chemotherapy resistance and proliferation of ovarian cancer cells. This review evaluates the recent advances, clinical applications, and future potential of nanoparticle-mediated delivery of siRNA therapeutics to target genes implicated in ovarian cancer.

Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons

“…C-Myc siRNA and doxorubicin-loaded cationic and anionic liposome poly cation-DNA nanoparticles significantly silence MDR1 gene expression, inhibit topoisomerase II, intercalate doxorubicin, and transcriptionally inhibit the resistant tumors and tumor regression. 69 A cationic liposome was prepared by Saad et al 70 for the co-delivery of MRP1 and Bcl2 siRNA in combination with doxorubicin. These liposomes efficiently suppress MDR effects by suppressing both anti-apoptotic signaling and drug efflux activity.…”

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

“…The application of siRNAs in the attempt to interfere with tumors has been primarily at the cell culture level rather than the whole organism [108] . Nevertheless, this approach does open up a new way to modify tumor cells and a broad variety of delivery systems have been employed in studies on OC [126][127][128][129][130][131][132][133] . Table 2 gives an overview on the deregulated circulating miRNAs detected in plasma, serum, ascites, urine and exosomes from OC patients and their function in EMT, migration, invasion and metastasis.…”

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

“…NPs are carriers providing an opportunity for therapeutic siRNAs to be delivered appropriately. Besides, the NPs lead to an effective entry into the cell and prevent the degradation of siRNAs inside the cell . The treatment with siRNA‐conjugated NPs would be suitable for ovarian cancer as there are several known gene targets, as well as anatomical accessibility for delivering the drug locally.…”

“…Besides, the NPs lead to an effective entry into the cell and prevent the degradation of siRNAs inside the cell. 44 The treatment with siRNA-conjugated NPs would be suitable for ovarian cancer as there are several known gene targets, as well as anatomical accessibility for delivering the drug locally. In addition, delivering the therapeutic siRNAs and chemotherapeutic agents at the same time may decrease the resistance to drugs.…”

“…In addition, delivering the therapeutic siRNAs and chemotherapeutic agents at the same time may decrease the resistance to drugs. 44 In the study by Han et al 45 , it was observed that delivering the siRNA with Arg-Gly-Asp chitosan NPs in ovarian cancer can act as an efficient method for silencing the genes (POSTN, FAK, and PLXDC1) that promote growth. Periostin (POSTN/Osteoblast-Specific Factor 2) has been shown to have a role in tumor progression and drug resistance.…”