Hendrik Setia Budi, - and Sepideh Izadi, - and Anton Timoshin, - and Sima Heydarzadeh Asl, - and Behzad Beyzai, - and Amir Ghaderpour, - and Fatemeh Alian, - and Farzaneh Sadat Eshaghi, - and Seyedeh Mahboubeh Mousavi, - and Behnam Rafiee, - and Afshin Nikkhoo, - and Armin Ahmadi, - and Hadi Hassannia, - and Majid Ahmadi, - and Mozhdeh Sojoodi, - and Farhad Jadidi-Niaragh, - (2021) Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT- chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth. Nanomedicine: Nanotechnology, Biology, and Medicine, 34 (-). pp. 1-14. ISSN 1549-9634

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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 siRNAencapsulated 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.

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