Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Paula Ofek; Marcelo Calderón; Fatemeh Sheikhi Mehrabadi; Adva Krivitsky; Shiran Ferber; Galia Tiram; Noga Yerushalmi; Sharon Kredo-Russo; Rachel Grossman; Zvi Ram; Rainer Haag; Ronit Satchi-Fainaro

doi:https://doi.org/10.1016/j.nano.2016.05.016

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Paula Ofek, Marcelo Calderón, Fatemeh Sheikhi Mehrabadi, Adva Krivitsky, Shiran Ferber, Galia Tiram, Noga Yerushalmi, Sharon Kredo-Russo, Rachel Grossman, Zvi Ram, Rainer Haag, Ronit Satchi-Fainaro

Tel Aviv University

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

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH₂), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH₂ carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH₂, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH₂-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH₂-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.

Original language	English
Pages (from-to)	2201-2214
Number of pages	14
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	12
Issue number	7
DOIs	https://doi.org/10.1016/j.nano.2016.05.016
State	Published - 1 Oct 2016

Keywords

Glioblastoma
MicroRNA-34a
Polyglycerol-based polyplex

All Science Journal Classification (ASJC) codes

Bioengineering
Molecular Medicine
Biomedical Engineering
General Materials Science
Medicine (miscellaneous)
Pharmaceutical Science

UN SDGs

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

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https://doi.org/10.1016/j.nano.2016.05.016

Cite this

Ofek, P., Calderón, M., Mehrabadi, F. S., Krivitsky, A., Ferber, S., Tiram, G., Yerushalmi, N., Kredo-Russo, S., Grossman, R., Ram, Z., Haag, R., & Satchi-Fainaro, R. (2016). Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex. Nanomedicine: Nanotechnology, Biology, and Medicine, 12(7), 2201-2214. https://doi.org/10.1016/j.nano.2016.05.016

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title = "Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex",

abstract = "Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.",

keywords = "Glioblastoma, MicroRNA-34a, Polyglycerol-based polyplex",

author = "Paula Ofek and Marcelo Calder{\'o}n and Mehrabadi, {Fatemeh Sheikhi} and Adva Krivitsky and Shiran Ferber and Galia Tiram and Noga Yerushalmi and Sharon Kredo-Russo and Rachel Grossman and Zvi Ram and Rainer Haag and Ronit Satchi-Fainaro",

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doi = "https://doi.org/10.1016/j.nano.2016.05.016",

language = "الإنجليزيّة",

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Ofek, P, Calderón, M, Mehrabadi, FS, Krivitsky, A, Ferber, S, Tiram, G, Yerushalmi, N, Kredo-Russo, S, Grossman, R, Ram, Z, Haag, R & Satchi-Fainaro, R 2016, 'Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 12, no. 7, pp. 2201-2214. https://doi.org/10.1016/j.nano.2016.05.016

TY - JOUR

T1 - Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

AU - Ofek, Paula

AU - Calderón, Marcelo

AU - Mehrabadi, Fatemeh Sheikhi

AU - Krivitsky, Adva

AU - Ferber, Shiran

AU - Tiram, Galia

AU - Yerushalmi, Noga

AU - Kredo-Russo, Sharon

AU - Grossman, Rachel

AU - Ram, Zvi

AU - Haag, Rainer

AU - Satchi-Fainaro, Ronit

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.

AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.

KW - Glioblastoma

KW - MicroRNA-34a

KW - Polyglycerol-based polyplex

UR - http://www.scopus.com/inward/record.url?scp=84977109996&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.nano.2016.05.016

DO - https://doi.org/10.1016/j.nano.2016.05.016

M3 - مقالة

SN - 1549-9634

VL - 12

SP - 2201

EP - 2214

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

IS - 7

ER -

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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