Abstract
Simple SummaryIn this review, we begin with the role of natural extracellular vesicles (EVs) in high-grade serous ovarian cancer (HGSOC). Then, we narrow our focus on the advantages of using EV-mimetic nanoparticles as a delivery vehicle for RNAi therapy and other chemotherapeutics. Furthermore, we discuss the challenges of the clinical translation of engineering EV mimetic drug delivery systems and the promising directions of further development.High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy among women. Several obstacles impede the early diagnosis and effective treatment options for ovarian cancer (OC) patients, which most importantly include the development of platinum-drug-resistant strains. Currently, extensive efforts are being put into the development of strategies capable of effectively circumventing the physical and biological barriers present in the peritoneal cavity of metastatic OC patients, representing a late stage of gastrointestinal and gynecological cancer with an extremely poor prognosis. Naturally occurring extracellular vesicles (EVs) have been shown to play a pivotal role in progression of OC and are now being harnessed as a delivery vehicle for cancer chemotherapeutics. However, there are limitations to their clinical application due to current challenges in their preparation techniques. Intriguingly, there is a recent drive towards the use of engineered synthetic EVs for the delivery of chemotherapeutics and RNA interference therapy (RNAi), as they show the promise of overcoming the obstacles in the treatment of OC patients. This review discusses the therapeutic application of EVs in OC and elucidates the potential use of engineered EV-mimetic nanoparticles as a delivery vehicle for RNAi therapy and other chemotherapeutics, which would potentially improve clinical outcomes of OC patients.
Highlights
It has become evident that extracellular vesicles (EVs) allow the exwith membrane receptors on target cells, innumerable proteins have been reported to be change of complex information; they are considered natural delivery systems ininvolved in this mechanism
It is likely that secreted factors and EV cargo differ between various subtypes of ovarian cancer (OC)
Several reports have suggested that EVs are able to mediate tumorigenesis, metastasis and drug resistance in OC through the transferring of their contents, i.e., proteins, double-stranded DNAs, messenger RNAs (mRNAs), miRNAs and lipids [93]
Summary
Ovarian epithelial cancer remains the most lethal gynecological malignancy among women worldwide [1,2]. EVs are bilayer lipid vesicles that contain various bioactive molecules, such as microRNAs (miRNAs), messenger RNAs (mRNAs) and proteins [19,20,21,22,23], as shown, highlighting their potential clinical applications such as therapeutic targets, diagnostic biomarkers, and drug-delivery vehicles [24]. Recent research has revealed an expanded range of involvement of these subtype of EVs with a diameter of 30–150 nm and are made up of different molecular lipid-bound intracellular communication a wide variety entities such as nanovesicles lipids, nucleicinacids, and proteins and addressvia it transferring to specific recipient cells of molecular cargos tohas recipient cellsanand coordination events. It has become evident that EVs allow the exwith membrane receptors on target cells, innumerable proteins have been reported to be change of complex information; they are considered natural delivery systems ininvolved in this mechanism.
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