Seyed Moein Moghimi

Prof. Seyed Moein Moghimi

1. School of Pharmacy, Newcastle University, Newcastle upon Tyne NE17RU, UK;
+4
orcid

Research Focus & Metrics

Academic Career Length

39Years (1988-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 June 2001 in Pharmacological Reviews
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Journal Article
Closed access
Seyed Moein MoghimiSeyed Moein Moghimi
Seyed Moein Moghimi
AHA. Christy Hunter
A. Christy Hunter
JMJ. Clifford Murray
J. Clifford Murray

1 March 2005 in The FASEB Journal
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Journal Article
Closed access
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Seyed Moein MoghimiSeyed Moein Moghimi
Seyed Moein Moghimi
AHA. Christy Hunter
A. Christy Hunter
JMJ. Clifford Murray
J. Clifford Murray

1 November 2003 in Progress in Lipid Research
Verified
Journal Article
Closed access
Seyed Moein MoghimiSeyed Moein Moghimi
Seyed Moein Moghimi
JSJ. Szebeni
J. Szebeni

1 June 2005 in Molecular Therapy
Verified
Journal Article
Open access
Seyed Moein MoghimiSeyed Moein Moghimi
Seyed Moein Moghimi
PSPeter Symonds
Peter Symonds
JMJ. Clifford Murray
J. Clifford Murray
AHA. Christy Hunter
A. Christy Hunter
GDGrazyna Debska
Grazyna Debska
Adam SzewczykAdam Szewczyk
Adam Szewczyk
Poly(ethylenimine) (PEI) is a cationic macromolecule commonly used in gene transfer/therapy protocols with high transfection efficiency both in vitro and in vivo. PEI is also cytotoxic, but the molecular basis of its cytotoxicity is poorly understood. Here, we have demonstrated that branched (25 kDa) and linear (750 kDa) PEI can both induce membrane damage and initiate apoptosis in three clinically relevant human cell lines (Jurkat T cells, umbilical vein endothelial cells, and THLE3 hepatocyte-like cells). We have defined Phase I toxicity as early necrotic-like changes (30 min) resulting from compromised membrane integrity, assessed by considerable lactate dehydrogenase release and phosphatidylserine translocation from the inner plasma membrane to the outer cell surface. Phase II cytotoxicity (24 h) was due to activation of a "mitochondrially mediated apoptotic program," resulting from PEI-induced channel formation in the outer mitochondrial membrane. This led to the release of proapoptotic cytochrome c, subsequent activation of caspase 3, and alteration in mitochondrial membrane potential as a result of caspase translocation into the mitochondria. The reported observations have important implications for the design and execution of gene therapy protocols as well for controlling intracellular distribution of drugs with cationic-based polymer-delivery systems.

1 January 2013 in Molecular Therapy
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Journal Article
Open access
RBRikke V Benjaminsen
Rikke V Benjaminsen
MMMaria A Mattebjerg
Maria A Mattebjerg
JHJonas R Henriksen
Jonas R Henriksen
Seyed Moein MoghimiSeyed Moein Moghimi
Seyed Moein Moghimi
TAThomas L Andresen
Thomas L Andresen
Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The “proton sponge ” hypothesis remains the most generally accepted mechanism, although it is heavily debated. This hypothesis is associated with the large buffering capacity of PEI and other polycations, which has been interpreted to cause an increase in lysosomal pH even though no conclusive proof has been provided. In the present study, we have used a nanoparticle pH sensor that was developed for pH measurements in the endosomal/lysosomal pathway. We have carried out quantitative measurements of lysosomal pH as a function of PEI content and correlate the results to the “proton sponge ” hypothesis. Our measurements show that PEI does not induce change in lysosomal pH as previously suggested and quantification of PEI concentrations in lysosomes makes it uncertain that the “proton sponge ” effect is the dominant mechanism of polyplex escape.

19 December 2016 in Nature Nanotechnology
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Journal Article
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FCFangfang Chen
Fangfang Chen
GWGuankui Wang
Guankui Wang
JGJames I. Griffin
James I. Griffin
BBBarbara Brenneman
Barbara Brenneman
NBNirmal K. Banda
Nirmal K. Banda
Dmitri SimbergDmitri Simberg
Dmitri Simberg