Advanced

Physicochemical properties of transferrin-associated lipopolyplexes and their role in biological activity

Penacho, Nuno; Rosa, Monica LU ; Lindman, Björn LU ; Miguel, Maria G.; Simoes, Sergio and Pedroso de Lima, Maria C. (2010) In Colloids and Surfaces B: Biointerfaces 76(1). p.207-214
Abstract
The combination of polyethylenimine (PEI), as a plasmid DNA pre-condensing agent, and cationic lipids has been reported to result in a synergistic effect on transfection. Recently, we have explored this effect by associating low-molecular weight PEIs with transferrin-associated lipoplexes using different cationic liposome formulations. The resulting lipopolyplexes that have shown to be the most efficient in mediating transfection were those prepared from cationic liposomes composed of DOTAP:Chol (associated or not with transferrin) and from a pH-sensitive liposome formulation (DOTAP:Chol: DOPE:CHEMS). In the present work, the physicochemical properties of these lipopolyplexes were studied aiming at establishing a correlation with their... (More)
The combination of polyethylenimine (PEI), as a plasmid DNA pre-condensing agent, and cationic lipids has been reported to result in a synergistic effect on transfection. Recently, we have explored this effect by associating low-molecular weight PEIs with transferrin-associated lipoplexes using different cationic liposome formulations. The resulting lipopolyplexes that have shown to be the most efficient in mediating transfection were those prepared from cationic liposomes composed of DOTAP:Chol (associated or not with transferrin) and from a pH-sensitive liposome formulation (DOTAP:Chol: DOPE:CHEMS). In the present work, the physicochemical properties of these lipopolyplexes were studied aiming at establishing a correlation with their transfection efficiency. For this purpose, the lipopolyplexes were characterized in terms of their morphology by performing ultrastructural Studies using cryo-TEM microscopy, investigating inner DNA Structure using circular dichroism and characterizing particle size by photon correlation spectroscopy. A correlation between efficiency of transfection and more compact inner DNA structure and smaller particle sizes (around 250 nm) was found. In addition, the visualization of liposomes and lipopolyplexes at the ultrastructural level revealed that the particles presenting enhanced transfection efficiencies are associated with higher electron density. Recently, PEI-based lipopolyplexes were reported to gain entry into the cell through the caveolae-mediated pathway. Based on the present finding that DOTAP:Chol liposomes exhibit the ability to form hexagonal structures when prepared at high concentrations, we propose that the lipopolyplexes containing DOTAP:Chol take advantage of such capacity to escape from the endocytotic vesicles, which will contribute to the observed high transfection efficiencies. (C) 2009 Elsevier B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Transferrin, Lipopolyplexes, Physicochemical properties, Transfection
in
Colloids and Surfaces B: Biointerfaces
volume
76
issue
1
pages
207 - 214
publisher
Elsevier
external identifiers
  • wos:000274767300031
  • scopus:74149085531
ISSN
1873-4367
DOI
10.1016/j.colsurfb.2009.10.034
language
English
LU publication?
yes
id
3ddac377-6106-41a7-8173-b13084a09f80 (old id 1568612)
date added to LUP
2010-03-17 15:05:26
date last changed
2018-05-29 09:55:40
@article{3ddac377-6106-41a7-8173-b13084a09f80,
  abstract     = {The combination of polyethylenimine (PEI), as a plasmid DNA pre-condensing agent, and cationic lipids has been reported to result in a synergistic effect on transfection. Recently, we have explored this effect by associating low-molecular weight PEIs with transferrin-associated lipoplexes using different cationic liposome formulations. The resulting lipopolyplexes that have shown to be the most efficient in mediating transfection were those prepared from cationic liposomes composed of DOTAP:Chol (associated or not with transferrin) and from a pH-sensitive liposome formulation (DOTAP:Chol: DOPE:CHEMS). In the present work, the physicochemical properties of these lipopolyplexes were studied aiming at establishing a correlation with their transfection efficiency. For this purpose, the lipopolyplexes were characterized in terms of their morphology by performing ultrastructural Studies using cryo-TEM microscopy, investigating inner DNA Structure using circular dichroism and characterizing particle size by photon correlation spectroscopy. A correlation between efficiency of transfection and more compact inner DNA structure and smaller particle sizes (around 250 nm) was found. In addition, the visualization of liposomes and lipopolyplexes at the ultrastructural level revealed that the particles presenting enhanced transfection efficiencies are associated with higher electron density. Recently, PEI-based lipopolyplexes were reported to gain entry into the cell through the caveolae-mediated pathway. Based on the present finding that DOTAP:Chol liposomes exhibit the ability to form hexagonal structures when prepared at high concentrations, we propose that the lipopolyplexes containing DOTAP:Chol take advantage of such capacity to escape from the endocytotic vesicles, which will contribute to the observed high transfection efficiencies. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Penacho, Nuno and Rosa, Monica and Lindman, Björn and Miguel, Maria G. and Simoes, Sergio and Pedroso de Lima, Maria C.},
  issn         = {1873-4367},
  keyword      = {Transferrin,Lipopolyplexes,Physicochemical properties,Transfection},
  language     = {eng},
  number       = {1},
  pages        = {207--214},
  publisher    = {Elsevier},
  series       = {Colloids and Surfaces B: Biointerfaces},
  title        = {Physicochemical properties of transferrin-associated lipopolyplexes and their role in biological activity},
  url          = {http://dx.doi.org/10.1016/j.colsurfb.2009.10.034},
  volume       = {76},
  year         = {2010},
}