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Simultaneous Inhibition of Cd73 and Il-6 Molecules by Sirna-Loaded Nanoparticles Prevents the Growth and Spread of Cancer Publisher Pubmed



Allahyari SE1 ; Hajizadeh F2, 3 ; Zekiy AO4 ; Mansouri N3 ; Gilan PS5 ; Mousavi SM3 ; Masjedi A3 ; Hassannia H6 ; Ahmadi M7 ; Mohammadi H8 ; Yousefi M7 ; Izadi S3 ; Zolbanin NM9 ; Jafari R10 Show All Authors
Authors
  1. Allahyari SE1
  2. Hajizadeh F2, 3
  3. Zekiy AO4
  4. Mansouri N3
  5. Gilan PS5
  6. Mousavi SM3
  7. Masjedi A3
  8. Hassannia H6
  9. Ahmadi M7
  10. Mohammadi H8
  11. Yousefi M7
  12. Izadi S3
  13. Zolbanin NM9
  14. Jafari R10
  15. Jadidiniaragh F3, 11
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  4. 4. Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russian Federation
  5. 5. Medical Biology Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
  6. 6. Immunogenetic Research Center, Faculty of Medicine and Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
  7. 7. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  8. 8. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  9. 9. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
  10. 10. Solid Tumor Research Center, Cellular and Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
  11. 11. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Nanomedicine: Nanotechnology# Biology# and Medicine Published:2021


Abstract

High concentrations of adenosine and interleukin (IL)-6 in the tumor microenvironment have been identified as one of the leading causes of cancer growth. Thus, we decided to inhibit the growth of cancer cells by inhibiting the production of adenosine and IL-6 in the tumor environment at the same time. For this purpose, we used chitosan-lactate-PEG-TAT (CLP-TAT) nanoparticles (NPs) loaded with siRNA molecules against CD73, an adenosine-producing enzyme, and IL-6. Proper physicochemical properties of the produced NPs led to high cell uptake and suppression of target molecules. Administration of these NPs to tumor-bearing mice (4T1 and CT26 models) greatly reduced the size of the tumor and increased the survival of the mice, which was accompanied by an increase in anti-tumor T lymphocyte responses. These findings suggest that combination therapy using siRNA-loaded CLP-TAT NPs against CD73 and IL-6 molecules could be an effective treatment strategy against cancer that needs further study. © 2021 Elsevier Inc.
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