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Silencing of Hif-1Α/Cd73 Axis by Sirna-Loaded Tat-Chitosan-Spion Nanoparticles Robustly Blocks Cancer Cell Progression Publisher Pubmed



Hajizadeh F1, 2 ; Moghadaszadeh Ardebili S1 ; Baghi Moornani M1 ; Masjedi A1 ; Atyabi F3 ; Kiani M3 ; Namdar A4 ; Karpisheh V5 ; Izadi S6 ; Baradaran B1 ; Azizi G7 ; Ghalamfarsa G8 ; Sabz G8 ; Yousefi M5 Show All Authors
Authors
  1. Hajizadeh F1, 2
  2. Moghadaszadeh Ardebili S1
  3. Baghi Moornani M1
  4. Masjedi A1
  5. Atyabi F3
  6. Kiani M3
  7. Namdar A4
  8. Karpisheh V5
  9. Izadi S6
  10. Baradaran B1
  11. Azizi G7
  12. Ghalamfarsa G8
  13. Sabz G8
  14. Yousefi M5
  15. Jadidiniaragh F1, 9
Show Affiliations
Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1714614411, Iran
  4. 4. Department of Oncology, Cross Cancer Institute, The University of Alberta, Edmonton, AB, Canada
  5. 5. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  8. 8. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
  9. 9. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: European Journal of Pharmacology Published:2020


Abstract

Induction of Hypoxia Inducible Factor (HIF) as a direct consequence of oxygen deficiency in tumor tissues is a potent stimulus of CD73 (ecto-5′-nucleotidase) expression. Hypoxic environment and CD73 overexpression are associated with altered metabolism, elevated cancer cell proliferation, and tumor vascularization. Herein, a delivery system was developed for silencing CD73 and HIF-1α gene using siRNA-loaded Superparamagnetic iron oxide (SPION) nanocarriers for cancer treatment. SPIONs were encapsulated with thiolated chitosan (TC) and trimethyl chitosan (TMC) for improving their stabilization and functionalization. The nanoparticles (NPs) were about 133 nm in size, spherical, and non-toxic, and the addition of TAT peptide (derived from HIV-1 TAT protein) to TMC-TC-SPIONs significantly increased their cellular uptake by cancer cells. The produced NPs could efficiently accumulate in the tumor site, indicating their stability and targeting ability in reaching the tumor region. TAT-conjugated TMC-TC-SPIONs containing siRNAs could significantly reduce the HIF-1α and CD73 expression levels in cancer cells. Following transfection, cancer cells showed a significant reduction in migration and proliferation. Moreover, siRNA-loaded NPs could effectively reduce tumor growth and angiogenesis, as investigated by the chick chorioallantoic membrane (CAM) assay. This study suggested that TAT-TMC-TC-SPIONs can be potential nanocarrier for gene transfection in cancer therapy. Moreover, the co-silencing of CD73 and HIF-1α can be assumed as a novel anti-cancer treatment strategy with high tumor suppression potential. © 2020 Elsevier B.V.
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