title: Time evolution of nanoparticle-protein corona in human plasma: relevance for targeted drug delivery.
abstract: When nanoparticles (NPs) enter a biological fluid (e.g., human plasma (HP)), proteins and other biomolecules adsorb on the surface leading to formation of a rich protein shell, referred to as "protein corona". This corona is dynamic in nature and its composition varies over time due to continuous protein association and dissociation events. Understanding the time evolution of the protein corona on the time-scales of a particle's lifetime in blood is fundamental to predict its fate in vivo. In this study, we used lipid NPs, the cationic lipid 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-Chol) and the zwitterionic lipid dioleoylphosphatidylethanolamine (DOPE), that are among the most promising nanocarriers both in vitro and in vivo. Here, we investigated the time evolution of DC-Chol-DOPE NPs upon exposure to HP. On time scales between 1 and 60 minutes, nanoliquid tandem mass spectrometry revealed that the protein corona of DC-Chol-DOPE NPs is mainly constituted of apolipoproteins (Apo A-I, Apo C-II, Apo D, and Apo E are the most enriched). Since the total apolipoprotein content is relevant, we exploited the protein corona to target PC3 prostate carcinoma cell line that expresses high levels of scavenger receptor class B type 1 receptor, which mediates the bidirectional lipid transfer between low-density lipoproteins, high-density lipoproteins, and cells. Combining laser scanning confocal microscopy experiments with flow cytometry we demonstrated that DC-Chol-DOPE/HP complexes enter PC3 cells by a receptor-mediated endocytosis mechanism.
authors: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.
authors: Ana Lilia
authors: AL
authors: Barrán-Berdón
authors: Daniela
authors: D
authors: Pozzi
authors: Giulio
authors: G
authors: Caracciolo
authors: Anna Laura
authors: AL
authors: Capriotti
authors: Giuseppe
authors: G
authors: Caruso
authors: Chiara
authors: C
authors: Cavaliere
authors: Anna
authors: A
authors: Riccioli
authors: Sara
authors: S
authors: Palchetti
authors: Aldo
authors: A
authors: Laganà
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties; D013997:Time Factors
chemical_list: D001798:Blood Proteins; D008055:Lipids