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

Area of Science:

• Nanotechnology
• Biomolecular Chemistry
• Analytical Chemistry

Background:

• The metabolite corona on nanoparticles is poorly understood, despite its distinct physicochemical and biological properties.
• Characterizing the metabolite corona is crucial for understanding nanoparticle interactions in complex biological fluids like human plasma.
• Existing methods lack comprehensive analysis of metabolite corona composition across diverse nanoparticle chemistries.

Purpose of the Study:

• To perform the first class-level mapping of the metabolite corona on chemically modified carbon nanotubes (CNTs).
• To investigate how polymer wrapping and surface defects on CNTs influence metabolite enrichment.
• To establish CNTs as tunable scaffolds for metabolite detection in biofluids.

Main Methods:

• Utilized untargeted liquid chromatography-mass spectrometry (LC-MS) to analyze metabolite corona composition on 25 chemically modified CNTs in human plasma.
• Employed complementary analytical conditions to detect and quantify approximately 9,000 metabolite features.
• Applied machine learning classifiers to annotate metabolite classes and analyze enrichment patterns.

Main Results:

• Identified polymer wrapping as a dominant factor, with DNA-wrapped CNTs enriching nonpolar lipids and PEG-wrapped CNTs favoring polar metabolites.
• Discovered that covalent quantum well defects on CNTs further modulate metabolite class enrichment in a structure- and chemistry-dependent manner.
• Observed specific effects of carboxyl aryl defects (enhancing amphiphilic lipid recruitment) and trifluoro aryl defects (suppressing single-chain amphiphiles, attenuating phospholipid depletion).

Conclusions:

• Engineered carbon nanotubes act as chemically tunable scaffolds for selective metabolite enrichment.
• The findings demonstrate the potential of CNT-based platforms for recruiting and detecting diverse, low-abundance small molecules in complex biofluids.
• This work provides a foundation for designing nanomaterials with tailored metabolite-binding properties for advanced diagnostics and research.