Nanoparticle-Based Detection of Oxidized Phospholipids by MALDI Mass Spectrometry: Nano-MALDI Approach

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 (Stubiger 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 ran...