DNA affects the composition of lipoplex protein corona: A proteomics approach

The distribution of drug delivery systems into the body is affected by plasma proteins adsorbed onto their surface. Furthermore, an exact understanding of the structure and morphology of drug carriers is fundamental to understand their role as gene delivery systems. In this work, the adsorption of h...

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Bibliographic Details
Published in:Proteomics (Weinheim) 2011-08, Vol.11 (16), p.3349-3358
Main Authors: Capriotti, Anna L., Caracciolo, Giulio, Caruso, Giuseppe, Foglia, Patrizia, Pozzi, Daniela, Samperi, Roberto, Laganà, Aldo
Format: Article
Language:English
Subjects:
Adsorption
Adult
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Biomedicine
Blood
Blood Proteins - chemistry
Blood Proteins - isolation & purification
Blood Proteins - metabolism
Cholesterol - analogs & derivatives
Cholesterol - chemistry
Chromatography, High Pressure Liquid
Compaction
Data processing
Deoxyribonucleic acid
Differences analysis
DNA
DNA - chemistry
DNA - metabolism
Drug delivery
Fibronectin
Fundamental and applied biological sciences. Psychology
Gene transfer
Gene Transfer Techniques
High-performance liquid chromatography
Histones
Humans
Immune system
LC-MS/MS
Lipid rafts
Liposomes
Liposomes - chemistry
Mass Spectrometry
Miscellaneous
Nanoconjugates - chemistry
Nanomedicine
nanoparticles
Particle Size
Phosphatidylethanolamines - chemistry
Plasma
Plasma proteins
Protein Binding
Protein composition
Proteins
Proteomics
Proteomics - methods
Reproducibility of Results
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Summary:The distribution of drug delivery systems into the body is affected by plasma proteins adsorbed onto their surface. Furthermore, an exact understanding of the structure and morphology of drug carriers is fundamental to understand their role as gene delivery systems. In this work, the adsorption of human plasma proteins bound to cationic liposomes and to their relative DNA lipoplexes was compared. A shotgun proteomics approach based on HPLC coupled to high resolution MS was used for an efficient identification of proteins adsorbed onto liposome and lipoplex surfaces. The distinct pattern of proteins adsorbed helps to better understand the DNA compaction process. The experimental evidence leads us to hypothesize that polyanionic DNA is associated to the lipoplex surface and can interact with basic plasma proteins. Such a finding is in agreement with recent results showing that lipoplexes are multilamellar DNA/lipid domains partially decorated with DNA at their surface. Proteomics experiments showed that the lipoplex corona is rich of biologically relevant proteins such as fibronectin, histones and complement proteins. Our results provide novel insights to understand how lipoplexes activate the immune system and why they are rapidly cleared from the blood stream. The differences in the protein adsorption data detected in the presented experiments could be the basis for the establishment of a correlation between protein adsorption pattern and in vivo fate of intravenously administered nanoparticles and will require some consideration in the future.
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.201000803