Nano-scale delivery systems for siRNA delivery in cancer therapy: New era of gene therapy empowered by nanotechnology

Environ Res. 2023 Dec 15;239(Pt 2):117263. doi: 10.1016/j.envres.2023.117263. Epub 2023 Oct 4.

Abstract

RNA interference (RNAi) is a unique treatment approach used to decrease a disease's excessive gene expression, including cancer. SiRNAs may find and destroy homologous mRNA sequences within the cell thanks to RNAi processes. However, difficulties such poor cellular uptake, off-target effects, and susceptibility to destruction by serum nucleases in the bloodstream restrict the therapeutic potential of siRNAs. Since some years ago, siRNA-based therapies have been in the process of being translated into the clinic. Therefore, the primary emphasis of this work is on sophisticated nanocarriers that aid in the transport of siRNA payloads, their administration in combination with anticancer medications, and their use in the treatment of cancer. The research looks into molecular manifestations, difficulties with siRNA transport, the design and development of siRNA-based delivery methods, and the benefits and drawbacks of various nanocarriers. The trapping of siRNA in endosomes is a challenge for the majority of delivery methods, which affects the therapeutic effectiveness. Numerous techniques for siRNA release, including as pH-responsive release, membrane fusion, the proton sponge effect, and photochemical disruption, have been studied to overcome this problem. The present state of siRNA treatments in clinical trials is also looked at in order to give a thorough and systematic evaluation of siRNA-based medicines for efficient cancer therapy.

Keywords: Drug resistance; Gene therapy; Nanocarriers; Nanoparticles; Targeted cancer therapy.

Publication types

  • Review

MeSH terms

  • Genetic Therapy
  • Humans
  • Nanoparticle Drug Delivery System
  • Nanoparticles* / chemistry
  • Nanotechnology / methods
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • RNA Interference
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering
  • Nanoparticle Drug Delivery System