Hakmin Mun¹* and Helen Townley^1,2

¹Nuffield Department of Women’s and Reproductive Health, University of Oxford, United Kingdom
²Department of Engineering Science, University of Oxford, United Kingdom

*Corresponding Author: Hakmin Mun, Nuffield Department of Women’s and Reproductive Health, University of Oxford, United Kingdom.

Received: July 27, 2021; Published: August 01, 2021

Abstract

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].

References

1. Doherty JA., et al. “Challenges and Opportunities in Studying the Epidemiology of Ovarian Cancer Subtypes”. Current Epidemiology Report3 (2017): 211-220.
2. Lheureux S., et al. “Epithelial ovarian cancer”. The Lancet10177 (2019): 1240-1253.
3. Chaurasiya S and Mishra V. “Biodegradable nanoparticles as theranostics of ovarian cancer: an overview”. Journal of Pharmacy and Pharmacology4 (2018): 435-449.
4. Mahmoodi Chalbatani G., et al. “Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach”. International Journal of Nanomedicine 14 (2019): 3111-3128.
5. Fire AZ. “Gene silencing by double-stranded RNA (Nobel Lecture)”. Angewandte Chemie 37 (2007): 6966-6984.
6. Zuckerman JE and Davis ME. “Clinical experiences with systemically administered siRNA-based therapeutics in cancer”. Nature Reviews Drug Discovery12 (2015): 843-856.
7. Krzystyniak J., et al. “Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer”. Annals of Oncology 27 (2016): i4-10.
8. Huang J., et al. “Knockdown of Hypoxia-Inducible Factor 1α (HIF-1α) Promotes Autophagy and Inhibits Phosphatidylinositol 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Ovarian Cancer Cells”. Medical Science Monitor 25 (2019): 4250-4263.
9. Xue T., et al. “SiRNA-Mediated RRM2 Gene Silencing Combined with Cisplatin in the Treatment of Epithelial Ovarian Cancer In Vivo: An Experimental Study of Nude Mice”. International Journal of Medical Sciences 11 (2019): 1510-1516.
10. Halbur C., et al. “siRNA-Conjugated Nanoparticles to Treat Ovarian Cancer”. SLAS TECHNOLOGY: Translating Life Sciences Innovation (2019).
11. Wang J., et al. “Delivery of siRNA therapeutics: barriers and carriers”. AAPS Journal4 (2010): 492-503.
12. Meng Z and Lu M. “RNA Interference-Induced Innate Immunity, Off-Target Effect, or Immune Adjuvant?” Frontiers in Immunology 8 (2017).
13. Tatiparti K., et al. “siRNA Delivery Strategies: A Comprehensive Review of Recent Developments”. Nanomaterials (Basel)4 (2017).
14. Kanasty R., et al. “Delivery materials for siRNA therapeutics”. Nature Materials11 (2013): 967-977.
15. Deleavey GF and Damha MJ. “Designing chemically modified oligonucleotides for targeted gene silencing”. Chemical Biology8 (2012): 937-954.
16. Peacock H., et al. “Chemical Modification of siRNA Bases To Probe and Enhance RNA Interference”. Journal of Organic Chemistry 18 (2011): 7295-7300.
17. Oliveira S., et al. “Targeted Delivery of siRNA”. Journal of Biomedicine and Biotechnology (2006).
18. Nour AM and Modis Y. “Endosomal vesicles as vehicles for viral genomes”. Trends in Cell Biology8 (2014): 449-454.
19. Kimchi-Sarfaty C., et al. “Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions”. Human Gene Therapy9 (2005): 1110-1115.
20. Babu A., et al. “Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy”. IEEE Transactions on NanoBioscience 8 (2016): 849-863.
21. Farra R., et al. “Strategies for Delivery of siRNAs to Ovarian Cancer Cells”. Pharmaceutics10 (2019).
22. Kim GH., et al. “Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer”. Drug Delivery1 (2018): 1394-1402.
23. Yang X., et al. “MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer”. Scientific Reports1 (2015): 8509.
24. Lee J., et al. “KSP siRNA/paclitaxel-loaded PEGylated cationic liposomes for overcoming resistance to KSP inhibitors: Synergistic antitumor effects in drug-resistant ovarian cancer”. Journal of Controlled Release 321 (2020): 184-197.
25. Roberts CM., et al. “Nanoparticle delivery of siRNA against TWIST to reduce drug resistance and tumor growth in ovarian cancer models”. Nanomedicine: Nanotechnology, Biology and Medicine3 (2017): 965-976.
26. Kotcherlakota R., et al. “Engineered fusion protein-loaded gold nanocarriers for targeted co-delivery of doxorubicin and erbB2-siRNA in human epidermal growth factor receptor-2+ ovarian cancer”. Journal of Materials Chemistry B34 (2017): 7082-7098.

Citation

Citation: Hakmin Mun and Helen Townley. “Nanoparticle Delivery of siRNAs in Epithelial Ovarian Cancer Treatment". Acta Scientific Medical Sciences 5.9 (2021): 01-04.

Copyright

Copyright: © 2021 Hakmin Mun and Helen Townley. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.