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Silencing of Il-6 and Stat3 by Sirna Loaded Hyaluronate-N,N,N-Trimethyl Chitosan Nanoparticles Potently Reduces Cancer Cell Progression Publisher Pubmed



Masjedi A1, 2 ; Ahmadi A3 ; Atyabi F4 ; Farhadi S5 ; Irandoust M1 ; Khazaeipoul Y5 ; Ghasemi Chaleshtari M1 ; Edalati Fathabad M1 ; Baghaei M4 ; Haghnavaz N6 ; Baradaran B7 ; Hojjatfarsangi M8, 9 ; Ghalamfarsa G10 ; Sabz G10 Show All Authors
Authors
  1. Masjedi A1, 2
  2. Ahmadi A3
  3. Atyabi F4
  4. Farhadi S5
  5. Irandoust M1
  6. Khazaeipoul Y5
  7. Ghasemi Chaleshtari M1
  8. Edalati Fathabad M1
  9. Baghaei M4
  10. Haghnavaz N6
  11. Baradaran B7
  12. Hojjatfarsangi M8, 9
  13. Ghalamfarsa G10
  14. Sabz G10
  15. Hasanzadeh S11
  16. Jadidiniaragh F7, 12

Source: International Journal of Biological Macromolecules Published:2020


Abstract

The immunosuppressive nature of the tumor microenvironment is a critical problem that should be considered before the design of immunotherapies. Interleukin (IL)-6 and its related downstream molecules such as signal transducer and activator of transcription (STAT)3 play an important role in the cancer progression, which can be considered as potential therapeutic targets. In the present study, we generated the active-targeted hyaluronate (HA) recoated N, N, N-trimethyl chitosan (TMC) nanoparticles (NPs) to deliver IL-6- and STAT3-specific small interfering RNAs (siRNAs) to the CD44-expressing cancer cells. We utilized the interaction between HA and CD44 to increase the specificity and efficacy of cellular uptake in NPs. The results showed that the synthesized NPs had efficient physicochemical characteristics, high transfection efficiency, low toxicity, and controlled siRNA release. siRNA-loaded NPs significantly inhibited the IL-6/STAT3 expression, which was associated with blockade of proliferation, colony formation, migration, and angiogenesis in cancer cells. These findings imply the potential of HA-TMC NPs as potent vectors in gene therapy and their application for the silencing of IL-6 and STAT3, as a novel anti-cancer combination therapeutic strategy, for the first time. © 2020
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