Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer

Reza Shahbazi; Elif Asik; Nermin Kahraman; Mustafa Turk; Bulent Ozpolat; Kezban Ulubayram

doi:10.2217/nnm-2017-0081

Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer

Reza Shahbazi, Elif Asik, Nermin Kahraman, Mustafa Turk, Bulent Ozpolat, Kezban Ulubayram

Houston Methodist

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.

Original language	English (US)
Pages (from-to)	1961-1973
Number of pages	13
Journal	Nanomedicine
Volume	12
Issue number	16
DOIs	https://doi.org/10.2217/nnm-2017-0081
State	Published - Aug 2017

Keywords

PEI-modified gold nanoparticles
eEF-2K siRNA
eEF2K
eukaryotic elongation factor 2 kinase
nanotherapeutics
triple-negative breast cancer

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
General Materials Science

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title = "Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer",

abstract = "Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.",

keywords = "PEI-modified gold nanoparticles, eEF-2K siRNA, eEF2K, eukaryotic elongation factor 2 kinase, nanotherapeutics, triple-negative breast cancer",

author = "Reza Shahbazi and Elif Asik and Nermin Kahraman and Mustafa Turk and Bulent Ozpolat and Kezban Ulubayram",

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year = "2017",

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doi = "10.2217/nnm-2017-0081",

language = "English (US)",

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T1 - Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer

AU - Shahbazi, Reza

AU - Asik, Elif

AU - Kahraman, Nermin

AU - Turk, Mustafa

AU - Ozpolat, Bulent

AU - Ulubayram, Kezban

PY - 2017/8

Y1 - 2017/8

N2 - Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.

AB - Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.

KW - PEI-modified gold nanoparticles

KW - eEF-2K siRNA

KW - eEF2K

KW - eukaryotic elongation factor 2 kinase

KW - nanotherapeutics

KW - triple-negative breast cancer

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ER -

Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer

Abstract

Keywords

ASJC Scopus subject areas

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