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Abstract In the last decade, nanoparticles (NPs) have become a key tool in medicine and biotechnology as drug delivery systems, biosensors and diagnostic devices. The composition and surface chemistry of NPs vary based on the materials used: typically organic polymers, inorganic materials, or lipids. Nanoparticle classes can be further divided into sub‐categories depending on the surface modification and functionalization. These surface properties matter when NPs are introduced into a physiological environment, as they will influence how nucleic acids, lipids, and proteins will interact with the NP surface. While small‐molecule interactions are easily probed using NMR spectroscopy, studying protein‐NP interactions using NMR introduces several challenges. For example, globular proteins may have a perturbed conformation when attached to a foreign surface, and the size of NP‐protein conjugates can lead to excessive line broadening. Many of these challenges have been addressed, and NMR spectroscopy is becoming a mature technique forin situanalysis of NP binding behavior. It is therefore not surprising that NMR has been applied to NP systems and has been used to study biomolecules on NP surfaces. Important considerations include corona composition, protein behavior, and ligand architecture. These features are difficult to resolve using classical surface and material characterization strategies, and NMR provides a complementary avenue of characterization. In this review, we examine how solution NMR can be combined with other analytical techniques to investigate protein behavior on NP surfaces.
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Solution NMR of Nanoparticles in Serum: Protein Competition Influences Binding Thermodynamics and Kinetics
The spontaneous formation of a protein corona on a nanoparticle surface influences the physiological success or failure of the synthetic nanoparticle as a drug carrier or imaging agent used in vivo . A quantitative understanding of protein-nanoparticle interactions is therefore critical for the development of nanoparticle-based therapeutics. In this perspective, we briefly discuss the challenges and limitations of current approaches used for studying protein-nanoparticle binding in a realistic biological medium. Subsequently, we demonstrate that solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to monitor protein competitive binding in a complex serum medium in situ . Importantly, when many serum proteins are competing for a gold nanoparticle (AuNP) surface, solution NMR is able to detect differences in binding thermodynamics, and kinetics of a tagged protein. Combined with other experimental approaches, solution NMR is an invaluable tool to understand protein behavior in the nanoparticle corona.
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- Award ID(s):
- 1818090
- PAR ID:
- 10337746
- Date Published:
- Journal Name:
- Frontiers in Physiology
- Volume:
- 12
- ISSN:
- 1664-042X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fphys.2021.715419
