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Age Shapes the Protein Corona: Unraveling the Impact of Biological Aging on Nanoparticle Identity and Function

ABSTRACT: Aging profoundly influences the composition of biological fluids, including the plasma proteome and lipidome, yet its effects on the protein coronas (PC) forming around nanoparticles (NPs) remain poorly understood. Here, we investigate how age-dependent changes in plasma proteins and lipids modulate the PC on silica NPs, affecting their physicochemical properties, cellular interactions, immune responses, and in vivo pharmacokinetics. Using plasma from C57 mice at 1, 9, and 18 months of age, we demonstrate that while lipid composition remains relatively stable, the PCs have subtle distinct age-related shifts. Proteomic analyses reveal altered abundances of proteins involved in endocytosis, cell adhesion, and immune regulation, ultimately influencing macrophage uptake and activation. In vitro experiments show that younger plasma-derived coronas enhance NP internalization, whereas older coronas diminish uptake but promote a stronger inflammatory response via complement activation and NF-κB signaling. In senescent macrophages, the pattern of NP internalization and immune activation differs, highlighting the complexity of age-associated changes in host-NP interactions. In vivo studies further confirm that NPs biodistribution, biocompatibility, and immunogenicity vary significantly with host age. our findings suggest age as a crucial yet underexplored factor in the design of nanomedicine, with significant implications for enhancing the safety and efficacy of both diagnostic and therapeutic nanomedicine technologies.

ORGANISM(S): Mus Musculus

SUBMITTER: Jigang Wang

PROVIDER: PXD062545 | iProX | Wed Apr 02 00:00:00 BST 2025

REPOSITORIES: iProX

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