Small interfering RNA (siRNA) to target genes and molecular pathways in glioblastoma therapy: Current status with an emphasis on delivery systems

Sepideh Mirzaei, Mahmood Khaksary Mahabady, Amirhossein Zabolian, Alireza Abbaspour, Peyman Fallahzadeh, Maedeh Noori, Farid Hashemi, Kiavash Hushmandi, Salman Daneshi, Alan Prem Kumar, Amir Reza Aref, Saeed Samarghandian, Pooyan Makvandi, Haroon Khan, Michael R. Hamblin, Milad Ashrafizadeh, Ali Zarrabi

Research output: Contribution to journalReview articlepeer-review

71 Citations (Scopus)

Abstract

Glioblastoma multiforme (GBM) is one of the worst brain tumors arising from glial cells, causing many deaths annually. Surgery, chemotherapy, radiotherapy and immunotherapy are used for GBM treatment. However, GBM is still an incurable disease, and new approaches are required for its successful treatment. Because mutations and amplifications occurring in several genes are responsible for the progression and aggressive behavior of GBM cells, genetic approaches are of great importance in its treatment. Small interfering RNA (siRNA) is a new emerging tool to silence the genes responsible for disease progression, particularly cancer. SiRNA can be used for GBM treatment by down-regulating genes such as VEGF, STAT3, ELTD1 or EGFR. Furthermore, the use of siRNA can promote the chemosensitivity of GBM cells. However, the efficiency of siRNA in GBM is limited via its degradation by enzymes, and its off-targeting effects. SiRNA-loaded carriers, especially nanovehicles that are ligand-functionalized by CXCR4 or angiopep-2, can be used for the protection and targeted delivery of siRNA. Nanostructures can provide a platform for co-delivery of siRNA plus anti-tumor drugs as another benefit. The prepared nanovehicles should be stable and biocompatible in order to be tested in human studies.

Original languageEnglish
Article number119368
JournalLife Sciences
Volume275
DOIs
Publication statusPublished - 15 Jun 2021

Keywords

  • Brain tumor
  • Delivery vehicles
  • Gene therapy
  • Glioblastoma multiforme
  • Nanoparticles
  • Small interfering RNA (siRNA)

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics (all)

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