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

doi:10.1016/j.nano.2021.102373

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 journal › Article › peer-review

31 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 language	English
Article number	102373
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	34
DOIs	https://doi.org/10.1016/j.nano.2021.102373
Publication status	Published - Jun 2021

Keywords

Chitosan
Hyaluronate
Hypoxia inducible factor
Nanoparticle
SPION
STAT3

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.nano.2021.102373

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Budi, H. S., Izadi, S., Timoshin, A., Asl, S. H., Beyzai, B., Ghaderpour, A., Alian, F., Eshaghi, F. S., Mousavi, S. M., Rafiee, B., Nikkhoo, A., Ahmadi, A., Hassannia, H., Ahmadi, M., Sojoodi, M., & Jadidi-Niaragh, F. (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, Article 102373. https://doi.org/10.1016/j.nano.2021.102373

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

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.",

keywords = "Chitosan, Hyaluronate, Hypoxia inducible factor, Nanoparticle, SPION, STAT3",

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

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jun,

doi = "10.1016/j.nano.2021.102373",

language = "English",

volume = "34",

journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",

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Budi, HS, Izadi, S, Timoshin, A, Asl, SH, Beyzai, B, Ghaderpour, A, Alian, F, Eshaghi, FS, Mousavi, SM, Rafiee, B, Nikkhoo, A, Ahmadi, A, Hassannia, H, Ahmadi, M, Sojoodi, M & Jadidi-Niaragh, F 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, vol. 34, 102373. https://doi.org/10.1016/j.nano.2021.102373

TY - JOUR

T1 - Blockade of HIF-1α and STAT3 by hyaluronate-conjugated TAT-chitosan-SPION nanoparticles loaded with siRNA molecules prevents tumor growth

AU - Budi, Hendrik Setia

AU - Izadi, Sepideh

AU - Timoshin, Anton

AU - Asl, Sima Heydarzadeh

AU - Beyzai, Behzad

AU - Ghaderpour, Amir

AU - Alian, Fatemeh

AU - Eshaghi, Farzaneh Sadat

AU - Mousavi, Seyedeh Mahboubeh

AU - Rafiee, Behnam

AU - Nikkhoo, Afshin

AU - Ahmadi, Armin

AU - Hassannia, Hadi

AU - Ahmadi, Majid

AU - Sojoodi, Mozhdeh

AU - Jadidi-Niaragh, Farhad

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - Chitosan

KW - Hyaluronate

KW - Hypoxia inducible factor

KW - Nanoparticle

KW - SPION

KW - STAT3

UR - http://www.scopus.com/inward/record.url?scp=85102900163&partnerID=8YFLogxK

U2 - 10.1016/j.nano.2021.102373

DO - 10.1016/j.nano.2021.102373

M3 - Article

C2 - 33667724

AN - SCOPUS:85102900163

SN - 1549-9634

VL - 34

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

M1 - 102373

ER -

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

Abstract

Keywords

UN SDGs

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