Nanoparticle based siRNA therapeutics for ovarian cancer overcoming drug resistance and future directions

Abstract

Recently, nanomedicine has made significant advancements, opening exciting new possibilities for treating a wide range of diseases. In this field, novel drug delivery systems (DDSs) are among the most noteworthy developments. The primary objective of DDSs is to ensure that treatments reach the intended targets while minimising adverse effects. In this context, nanoparticle (NP)-based DDSs have shown remarkable potential in oncology, particularly for ovarian cancer (OC), the deadliest type of gynecological cancer due to its mortality rate and the occurrence of treatment resistance. In this review, we provide a comprehensive description of the different types of NPs being explored for OC treatment, with a special emphasis on their involvement in delivering small interfering RNA (siRNA) treatments. We review various NP platforms shedding light on how they enhance drug stability, enable controlled release, and reduce toxicity. We also explore the techniques used to synthesise these NPs, emphasizing how modifying their physical and chemical properties can improve their ability to target cancer cells effectively. We also discuss the importance of 3D-tumor models, which more accurately replicate the complexity of real tumors. This enables us to examine the ability of NPs to penetrate tumors and consequently therapies are delivered in a setting that really resembles real-life situations. Recent advances in RNA-based therapeutics through DDS offer a highly targeted approach to shutting down oncogenes and drug resistance mechanisms, making them a powerful strategy to complement conventional treatments. The analysis of clinical trials results indicate a requirement for further studies in order to refine the clinical applications of drugs based on siRNAs. Despite the ongoing challenges, NP-based DDSs are paving the way for more precise and personalized OC treatments.

Keywords: Biomimetic nanoparticles; Microfluidics; Nanoparticles; Ovarian cancer; siRNA delivery.

Fig. 1

Explanatory diagram of the different structure and production phases in the preparation of biomimetic NPs. Reproduced with permission from [76]

Fig. 2

Microfluidic set-up illustration. Reproduced with permission from [116]

Fig. 3

Graphical representation of the most widely used geometries of microfluidic devices. A T-junction, B Staggered herringbone micromixer (SHM), C Hydrodynamic flow focusing (HFF)