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
N1 - Publisher Copyright:
© 2016 The Authors.
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 - 10.1016/j.nano.2016.05.016
DO - 10.1016/j.nano.2016.05.016
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:84977109996
SN - 1549-9634
VL - 12
SP - 2201
EP - 2214
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 7
ER -
