TY - JOUR

T1 - A comprehensive analysis of liposomal biomolecular corona upon human plasma incubation: The evolution towards the lipid corona

AU - La Barbera, Giorgia

AU - Capriotti, Anna Laura

AU - Caracciolo, Giulio

AU - Cavaliere, Chiara

AU - Cerrato, Andrea

AU - Montone, Carmela Maria

AU - Piovesana, Susy

AU - Pozzi, Daniela

AU - Quagliarini, Erica

AU - Laganà, Aldo

N1 - CURIS 2020 NEXS 008

PY - 2020

Y1 - 2020

N2 - When drug nanocarriers enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BMC) mainly constituted by proteins. Although a deep investigation has been performed on the composition of BMC in terms of proteins, scarce attention has been posed to low molecular weight metabolites present in human plasma. In this work, for the first time, the investigation of the BMC of liposomal nanoparticles (NPs) constituted by 1,2-dioleoyl-3-trimethylammonium-propane polar lipid has been carried out by an ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry based untargeted metabolomics approach. Compounds were tentatively identified based on matches with online databases and comparison of MS/MS spectra with available spectral libraries. Moreover, a comparison of three metabolite extraction strategies, including an ultrafiltration membrane based protocol, a methanol extraction based protocol, and Wessel & Flügge protocol, was performed. Methanol extraction procedure resulted in the widest metabolic coverage of liposomal NP BMC. A total of 193 metabolites has been tentatively identified, 166 of which belonged to the class of lipids including phospholipids, steroids, carnitines, fatty alcohols, diglycerides and fatty acids. The high abundance of lipids in the BMC can be explained by the adsorption of plasma lipoproteins onto liposome surface, confirming previous works on other kinds of NPs. Lipids are important bioactive molecules, which could impact NP circulation and uptake by cells. Extending the investigation of BMC beyond the protein corona and towards the “lipid corona” may be the keystone of a better understanding and control of NP fate in human body.

AB - When drug nanocarriers enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BMC) mainly constituted by proteins. Although a deep investigation has been performed on the composition of BMC in terms of proteins, scarce attention has been posed to low molecular weight metabolites present in human plasma. In this work, for the first time, the investigation of the BMC of liposomal nanoparticles (NPs) constituted by 1,2-dioleoyl-3-trimethylammonium-propane polar lipid has been carried out by an ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry based untargeted metabolomics approach. Compounds were tentatively identified based on matches with online databases and comparison of MS/MS spectra with available spectral libraries. Moreover, a comparison of three metabolite extraction strategies, including an ultrafiltration membrane based protocol, a methanol extraction based protocol, and Wessel & Flügge protocol, was performed. Methanol extraction procedure resulted in the widest metabolic coverage of liposomal NP BMC. A total of 193 metabolites has been tentatively identified, 166 of which belonged to the class of lipids including phospholipids, steroids, carnitines, fatty alcohols, diglycerides and fatty acids. The high abundance of lipids in the BMC can be explained by the adsorption of plasma lipoproteins onto liposome surface, confirming previous works on other kinds of NPs. Lipids are important bioactive molecules, which could impact NP circulation and uptake by cells. Extending the investigation of BMC beyond the protein corona and towards the “lipid corona” may be the keystone of a better understanding and control of NP fate in human body.

KW - Corona

KW - High resolution mass spectrometry

KW - Lipidomics

KW - Lipoproteins

KW - Liposome

KW - Metabolomics

UR - http://www.scopus.com/inward/record.url?scp=85074463532&partnerID=8YFLogxK

U2 - 10.1016/j.talanta.2019.120487

DO - 10.1016/j.talanta.2019.120487

M3 - Journal article

C2 - 31892008

AN - SCOPUS:85074463532

VL - 209

JO - Talanta

JF - Talanta

SN - 0039-9140

M1 - 120487

ER -