Silencing of IL-6 and STAT3 by siRNA loaded hyaluronate-N,N,N-trimethyl chitosan nanoparticles potently reduces cancer cell progression

Masjedi, A and Ahmadi, A and Atyabi, F and Farhadi, S and Irandoust, M and Khazaei-Poul, Y and Ghasemi Chaleshtari, M and Edalati Fathabad, M and Baghaei, M and Haghnavaz, N and Baradaran, B and Hojjat-Farsangi, M and Ghalamfarsa, G and Sabz, G and Hasanzadeh, S and Jadidi-Niaragh, F (2020) Silencing of IL-6 and STAT3 by siRNA loaded hyaluronate-N,N,N-trimethyl chitosan nanoparticles potently reduces cancer cell progression. International Journal of Biological Macromolecules, 149. pp. 487-500. ISSN 01418130

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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.

Item Type: Article
Uncontrolled Keywords: CD44 Hyaluronate Interleukine-6 Nanoparticle Signal transducer and activator of transcription 3 siRNA Trimethyl chitosan
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Research Center > Persian Gulf Marine Biotechnology Research Center
Depositing User: خدیجه شبانکاره
Date Deposited: 22 Dec 2020 10:23
Last Modified: 22 Dec 2020 10:23
URI: http://eprints.bpums.ac.ir/id/eprint/9050

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