Mass Spectrometry Imaging Reveals the In Situ Distribution and Metabolic Effects of Fullerenes

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Fullerene-based nanoparticles have been extensively developed and applied in biological immunotherapy due to their unique immunomodulatory properties. However, current methods for investigating their biodistribution predominantly rely on fluorescent labeling, which limits our understanding of the true biodistribution of fullerenes at both organ and suborgan levels, as well as their impact on organ-specific metabolism. In this study, we utilized laser desorption ionization and matrix-assisted laser desorption/ionization mass spectrometry imaging to achieve simultaneous in vivo mapping of fullerenes and their associated metabolites. Following tail-vein injection into mice, fullerenes were primarily localized in the liver and spleen with significant enrichment in the red pulp of the spleen. Notably, fullerene accumulation in normal tissues resulted in substantial alterations in endogenous metabolic pathways, particularly those related to pyrimidine, purine, and energy metabolism. This approach provides valuable insights into the metabolic effects of fullerenes in vivo, offering a foundation for further investigation into their biological and therapeutic implications.