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  • Targeted siRNA delivery in cervical cancer using liposomal nanoparticles

  • Samira Mohammadi Khorramabadi,1 Elham Kamalkazemi,2 Abdolvahab moradi,3 Hossein Bannazadeh Baghi,4,*
    1. Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciense, Golestan, Iran
    2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
    3. Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciense, Golestan, Iran
    4. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran


  • Introduction: Cervical cancer is primarily driven by persistent infection with high-risk human papillomavirus (HPV), particularly through the expression of E6 and E7 oncogenes. Small interfering RNAs (siRNAs) represent a promising strategy for silencing these genes, but their low stability and poor cellular uptake are the main challenges to its clinical application. Lipid nanocarriers can help overcome to these obstacles by protecting siRNA from enzymatic degradation and facilitating endocytosis(1, 2). This study aimed to review the efficacy, routes of administration, and immune responses of siRNA-loaded lipid nanoparticles in preclinical models of cervical cancer.
  • Methods: This study was conducted as a Structured Review based on searches of the reputable databases PubMed, Scopus, and Web of Science. Keywords used were siRNA, papillomavirus, Cervical Cancer, Liposome. The inclusion criteria were original research articles evaluating liposomal delivery of siRNA targeting HPV oncogenes. Five preclinical studies investigating lipid nanocarriers such as cationic, pegylated, or hybrid liposomes containing siRNA targeting E6, E7, Bcl-2, or MCL-1 genes in the treatment of cervical cancer were selected.
  • Results: Analysis of data extracted from selected studies showed that the use of lipid nanocarriers, especially cationic (2) and pegylated liposomes (3), significantly increased systemic stability and cellular uptake by protecting siRNA from enzymatic degradation and facilitating endocytosis. This targeted and efficient delivery resulted in simultaneous silencing of oncogenic genes E6 and E7 in high-risk strains HPV16 and HPV18, restoration of the p53 and Retinoblastoma protein (pRb) tumor suppressor pathways, cell cycle arrest, and induction of apoptosis in in vitro models. Furthermore, administration of these nanoparticles either systemically (4) or intraperitoneally (5), not only inhibited tumor growth or completely cleared tumors but also significantly enhanced the antitumor immune response by inducing autophagy and immunogenic cell death (ICD).
  • Conclusion: Lipid nanocarriers are recognized as a very promising therapeutic platform for the delivery of siRNA in cervical cancer.
  • Keywords: Papillomavirus, Cervical Cancer, siRNA, Liposome

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