(151h) Protein Corona Formation on Single-Walled Carbon Nanotubes for Applications in Biological Environments

Engineered nanoparticles such as single-walled carbon nanotubes (SWCNTs) are increasingly used for biological sensing, imaging, and delivery applications owing to their distinctive optical and physical properties. SWCNT-based probes operate at spatiotemporal scales necessary to capture information on chemical signaling such as neurotransmission in the brain¹, and can deliver functional biological cargoes to tissues for genetic tranformations². The critical – and often overlooked – challenge with these nanoscale tools is understanding the fundamental mechanisms of interaction between the nanoprobe and the system they are designed to query. When a nanoparticle enters a biological system, the surface becomes coated with proteins to form the ‘protein corona’. Binding of proteins to the nanoparticle not only affects the structure and function of the native biomolecules, but has the added consequences of affecting nanoparticle biodistribution, masking the intended imaging or delivery function of the nanoparticle, and unpredictably re-defining the nanoparticle chemical identity³.

To apply nanoscale tools in biological systems, it is crucial to understand the mechanisms and outcomes of protein corona formation. We present results on protein corona composition and binding dynamics for our SWCNT-based probes upon exposure to two biological fluids of interest: human blood plasma and cerebrospinal fluid. A selective adsorption assay with characterization by protein mass spectrometry reveals the unique composition of nanoparticle coronae, with identification of key corona proteins. Variation of incubation conditions provides insight on thermodynamic factors and dominant interactions driving protein corona formation. Next, the dynamic exchange of biomolecules in the corona phase is studied by a combination of near-infrared and visible fluorescence monitoring of the SWCNT and fluorophore-labeled proteins, respectively. Ultimately, a ‘designer corona’ strategy will be implemented to cloak the nanoprobes against untimely clearance pathways, to impart targeting abilities on a cellular level, and to encourage desired biodistribution outcomes on an organism level. Probing the corona composition, driving forces of formation, and timescales upon which the protein corona forms will inform figures of merit for the predictive design and synthesis of nanotechnology-based tools to be applied in protein-rich environments.

References

[1] Beyene, A. G. et al. Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor. bioRxiv 356543 (2018). doi:10.1101/356543

[2] Demirer, G. S. et al. High aspect ratio nanomaterials enable delivery of functional genetic material without DNA integration in mature plants. Nature Nanotechnology 1 (2019). doi:10.1038/s41565-019-0382-5

[3] Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nature Materials 8, 543–557 (2009).