BMI-Dependent Nanoparticle Protein Corona Signatures in Late Pregnancy: Insights into Metabolic and Immune Modulation

When nanoparticles (NPs) are exposed to human plasma, a selective layer of proteins, known as the protein corona (PC), forms on their surface. This phenomenon can enrich the NP's PC with low-abundance, high-affinity proteins, enabling the detection of rare or subtle proteomic changes often missed in direct plasma analysis. We investigated how Body Mass Index (BMI) influences the plasma proteome of women in their third trimester of pregnancy to better understand the links between metabolic health and late-pregnancy physiology. Commercial polystyrene NPs were incubated with plasma from pregnant individuals sorted by BMI. The PC composition was analyzed via liquid chromatography mass spectrometry (LC-MS) based proteomics and physicochemical characterization via transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analyses. Our findings revealed 13 significant proteins between obese and normal weight groups, including significantly increased expression of Apolipoprotein(a), a plasma lipoprotein that, in elevation, is a risk factor for atherosclerotic cardiovascular disease (ASCVD); as well as decreased expression of Human Leukocyte Antigen (HLA) Class I histocompatibility antigen, a key immune system protein in self-peptide presentation. Our findings highlight the NPs' PC as a sensitive, translational platform for uncovering pregnancy-related biomarkers and risk factors.