Cytotoxicity mechanism of non-viral carriers polyethylenimine and poly-l-lysine using real time high-content cellular assay

Cationic polymers polyethylenimine (PEI) and poly-l-lysine (PLL) used as non-viral gene/drug delivery vehicles, showed high cytotoxicity but their molecular mechanisms of toxicity have been inadequately understood. Therefore, we tried to investigate the toxicity pathway triggered by these polymers t...

Full description

Saved in:
Bibliographic Details
Published in:Polymer (Guilford) 2014-09, Vol.55 (20), p.5178-5188
Main Authors: Paul, Avijit, Eun, Chae-Jung, Song, Joon Myong
Format: Article
Language:English
Subjects:
Apoptosis
Assaying
Cellular
Cytotoxicity
High-content screening
Pathways
Polyetherimides
Polyethylenimine
Polymer
Real time
Toxicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cationic polymers polyethylenimine (PEI) and poly-l-lysine (PLL) used as non-viral gene/drug delivery vehicles, showed high cytotoxicity but their molecular mechanisms of toxicity have been inadequately understood. Therefore, we tried to investigate the toxicity pathway triggered by these polymers through a high-content cellular imaging technique. The results revealed that PEI induced apoptosis via an intrinsic pathway, whereas PLL showed cytotoxicity through both intrinsic and extrinsic caspase cascade. Both PEI and PLL provide different apoptotic activities on HepG2 cells depending on their molecular weight. The degree of apoptosis of PEI also depends on its structure. The branched PEI showed higher cytotoxicity than linear PEI. This observation was verified through Annexin V-FITC/PI assay and real-time high-content monitoring of cytosolic calcium, mitochondrial membrane disruption, and caspase-3 activation methods. The study therefore provides important implications on the molecular mechanisms of PEI and PLL induced cytotoxicity. [Display omitted]
ISSN:0032-3861
1873-2291
DOI:10.1016/j.polymer.2014.08.043