Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT-chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth

Hendrik Setia Budi, Sepideh Izadi, Anton Timoshin, Sima Heydarzadeh Asl, Behzad Beyzai, Amir Ghaderpour, Fatemeh Alian, Farzaneh Sadat Eshaghi, Seyedeh Mahboubeh Mousavi, Behnam Rafiee, Afshin Nikkhoo, Armin Ahmadi, Hadi Hassannia, Majid Ahmadi, Mozhdeh Sojoodi, Farhad Jadidi-Niaragh

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

HIF-1α and STAT3 are two of the critical factors in the growth, proliferation, and metastasis of cancer cells and play a crucial role in inhibiting anti-cancer immune responses. Therefore, we used superparamagnetic iron oxide (SPION) nanoparticles (NPs) coated with thiolated chitosan (ChT) and trimethyl chitosan (TMC) and functionalized with hyaluronate (H) and TAT peptide for delivery of siRNA molecules against STAT3 and HIF-1α to cancer cells both in vivo and in vitro. The results indicated that tumor cell transfection with siRNA-encapsulated NPs robustly inhibited proliferation and migration and induced apoptosis in tumor cells. Furthermore, simultaneous silencing of HIF-1α and STAT3 significantly repressed cancer development in two different tumor types (4T1 breast cancer and CT26 colon cancer) which were associated with upregulation of cytotoxic T lymphocytes and IFN-γ secretion. The findings suggest inhibiting the HIF-1α/STAT3 axis by SPION-TMC-ChT-TAT-H NPs as an effective way to treat cancer.

Original languageEnglish
Article number102373
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume34
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Chitosan
  • Hyaluronate
  • Hypoxia inducible factor
  • Nanoparticle
  • SPION
  • STAT3

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