title: DNA affects the composition of lipoplex protein corona: a proteomics approach.
abstract: 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.
authors.affiliation: Dipartimento di Chimica, Sapienza Università di Roma, Roma, Italy. annalaura.capriotti@uniroma1.it
authors.forename: Anna L
authors.initials: AL
authors.lastname: Capriotti
authors.forename: Giulio
authors.initials: G
authors.lastname: Caracciolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caruso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Foglia
authors.forename: Daniela
authors.initials: D
authors.lastname: Pozzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Samperi
authors.forename: Aldo
authors.initials: A
authors.lastname: Laganà
mesh_terms: D000327:Adsorption; D000328:Adult; D001798:Blood Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D013058:Mass Spectrometry; D058726:Nanoconjugates / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D001798:Blood Proteins; D008081:Liposomes; D058726:Nanoconjugates; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D004247:DNA; D002784:Cholesterol