title: Nanoparticle-based detection of oxidized phospholipids by MALDI mass spectrometry: nano-MALDI approach.
abstract: In this paper we present a pioneering approach exploiting nanoparticles (NPs) for the "on-probe" (i.e., directly from the NP-surface) monitoring of OxPLs by MALDI-MS (i.e., the Nano-MALDI approach). The "electrophilic interaction" with either metal oxide (e.g., ZrO2) or surface-functionalized Fe3O4 core-shell superparamagnetic NPs (100 nm diameter) was exploited for the direct enrichment of short-chain carboxylic (CARBO)-OxPLs, whereas detection of aldehydic (ALDO)-OxPLs was enabled by prior derivatization with bifunctional carbonyl-reactive reagents containing a negatively charged moiety (e.g., 4-AA) followed by NP-binding. Polyetheramine (PEA)-NPs were found best suited in terms of solvent stability, binding efficiency and compatibility with MALDI-MS analysis. For quantitative analysis of the OxPLs a recently introduced MALDI-QIT-TOF-MS/MS platform (Stübiger et al. Atherosclerosis 2012, 224, 177-186) was employed and cross-validated by LC-ESI-SRM-MS/MS. The sensitivity was found in the sub-nanomolar range (LOD ~200 pM), which is 1-4 orders of magnitude higher than necessary for detection of individual OxPLs under normal and diseased conditions in vivo (e.g., in mouse plasma or human lipoproteins). Consequently, the Nano-MALDI approach shows the potential to serve as novel platform for the screening of OxPLs in biological samples and the development of clinical diagnostic tests in the future.
authors.affiliation: Center for Physiology and Pharmacology, Medical University of Vienna , Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Stübiger
authors.forename: Michael
authors.initials: M
authors.lastname: Wuczkowski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bicker
authors.forename: Omar
authors.initials: O
authors.lastname: Belgacem
mesh_terms: D000818:Animals; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood* / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D015040:Zirconium / Q000737:chemistry
chemical_list: D058185:Magnetite Nanoparticles; D010743:Phospholipids; D015040:Zirconium; C028541:zirconium oxide