Chemically Engineered Carbon Nanotubes Map Class-Selective Metabolite Enrichment from Human Plasma

The spontaneous adsorption of biomolecules onto nanoparticle surfaces has been extensively characterized at the protein level, but the metabolite corona remains poorly defined while being physicochemically and biologically distinctive. Herein, we report the first class-level mapping of metabolite corona composition across 25 chemically modified carbon nanotubes in human plasma using untargeted liquid chromatography-mass spectrometry. Complementary analytical conditions detected approximately 9,000 metabolite features, of which over 5,000 yielded valid corona-versus-plasma enrichment measurements. Machine learning classifiers extended metabolite class annotations from 10-45% to the full detected set, enabling systematic analysis of class-level enrichment patterns. We find that polymer wrapping dominates corona composition, with DNA wrapping selectively enriching nonpolar lipids and PEG wrapping favoring polar metabolites. Within each polymer background, covalent quantum well defects further modulate class-level enrichment in a structure- and chemistry-dependent manner. Carboxyl aryl defects broadly enhance amphiphilic lipid recruitment, while trifluoro aryl defects suppress single-chain amphiphilic species but attenuate depletion of double-chain phospholipids. Our findings demonstrate that engineered nanotubes can serve as chemically tunable, selective scaffolds for metabolite enrichment, potentially enhancing the capability of nanotube-based platforms to recruit and detect structurally diverse, low-abundance small molecules in complex biofluids.