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1. Nanoparticle protein corona: from structure and function to therapeutic targeting

   https://doi.org/10.1039/D2LC00799A  

   Bashiri, Ghazal ; Padilla, Marshall S. ; Swingle, Kelsey L. ; Shepherd, Sarah J. ; Mitchell, Michael J. ; Wang, Karin ( March 2023 , Lab on a Chip)

   Nanoparticle (NP)-based therapeutics have ushered in a new era in translational medicine. However, despite the clinical success of NP technology, it is not well-understood how NPs fundamentally change in biological environments. When introduced into physiological fluids, NPs are coated by proteins, forming a protein corona (PC). The PC has the potential to endow NPs with a new identity and alter their bioactivity, stability, and destination. Additionally, the conformation of proteins is sensitive to their physical and chemical surroundings. Therefore, biological factors and protein–NP-interactions can induce changes in the conformation and orientation of proteins in vivo . Since the function of a protein is closely connected to its folded structure, slight differences in the surrounding environment as well as the surface characteristics of the NP materials may cause proteins to lose or gain a function. As a result, this can alter the downstream functionality of the NPs. This review introduces the main biological factors affecting the conformation of proteins associated with the PC. Then, four types of NPs with extensive utility in biomedical applications are described in greater detail, focusing on the conformation and orientation of adsorbed proteins. This is followed by a discussion on the instances in which the conformation of adsorbed proteins can be leveraged for therapeutic purposes, such as controlling protein conformation in assembled matrices in tissue, as well as controlling the PC conformation for modulating immune responses. The review concludes with a perspective on the remaining challenges and unexplored areas at the interface of PC and NP research. 

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2. Protein Interactions with Nanoparticle Surfaces: Highlighting Solution NMR Techniques

   https://doi.org/10.1002/ijch.201900080  

   Randika Perera, Y. ; Hill, Rebecca A. ; Fitzkee, Nicholas C. ( September 2019 , Israel Journal of Chemistry)

   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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3. Nanoparticle Diffusion in Crowded Polymer Nanocomposite Melts

   https://doi.org/10.1021/acsmacrolett.4c00438  

   Wang, Kaitlin ; Winey, Karen I ( September 2024 , ACS Macro Letters)

   This study examines nanoparticle diffusion in crowded polymer nanocomposites by diffusing small Al2O3 nanoparticles (NPs) in SiO2-loaded P2VP matrices. Time-of-flight secondary ion mass spectroscopy (ToF-SIMS) measures Al2O3 NP diffusion coefficients within a homogeneous PNC background of larger, immobile SiO2 NPs. By developing a geometric model for the average interparticle distance in a system with two NP sizes, we quantify nanocomposite confinement relative to the Al2O3 NP size with a bound layer. At low SiO2 concentrations, Al2O3 NP diffusion aligns with the neat polymer results. In more crowded nanocomposites with higher SiO2 concentrations where the interparticle distance approaches the size of the mobile Al2O3 NP, the 6.5 nm Al2O3 NPs diffuse faster than predicted by both core–shell and vehicular diffusion models. Relative to our previous studies of NPs diffusing into polymers, these findings demonstrate that the local environment in crowded systems significantly complicates NP diffusion behavior and the bound layer lifetimes. 

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4. Detecting bound polymer layers in attractive polymer–nanoparticle hybrids

   https://doi.org/10.1039/D1NR02395K  

   Emamy, Hamed ; Starr, Francis W. ; Kumar, Sanat K. ( August 2021 , Nanoscale)

   When polymer–nanoparticle (NP) attractions are sufficiently strong, a bound polymer layer with a distinct dynamic signature spontaneously forms at the NP interface. A similar phenomenon occurs near a fixed attractive substrate for thin polymer films. While our previous simulations fixed the NPs to examine the dilute limit, here, we allow the NP to move. Our goal is to investigate how NP mobility affects the signature of the bound layer. For small NPs that are relatively mobile, the bound layer is slaved to the motion of the NP, and the signature of the bound layer relaxation in the intermediate scattering function essentially disappears. The slow relaxation of the bound layer can be recovered when the scattering function is measured in the NP reference frame, but this process would be challenging to implement in experimental systems with multiple NPs. Instead, we use the counterintuitive result that the NP mass affects its mobility in the nanoscale limit, along with the more expected result that the bound layer increases the effective NP mass, to suggest that the signature of the bound polymer manifests as a change in NP diffusivity. These findings allow us to rationalize and quantitatively understand the results of recent experiments focused on measuring NP diffusivity with either physically adsorbed or chemically end-grafted chains. 

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5. Adsorption and Molecular Display of a Redox-Active Protein on Gold Nanoparticle Surfaces

   https://doi.org/10.1021/acs.langmuir.3c01983  

   Hoang, Khoi Nguyen ; Murphy, Catherine J. ( October 2023 , Langmuir)

   Engineered gold nanoparticles (AuNPs) have great potential in many applications due to their tunable optical properties, facile synthesis, and surface functionalization via thiol chemistry. When exposed to a biological environment, NPs are coated with a protein corona that can alter the NPs’ biological identity but can also affect the proteins’ structures and functions. Protein disulfide isomerase (PDI) is an abundant protein responsible for the disulfide formation and isomerization that contribute to overall cell redox homeostasis and signaling. Given that AuNPs are widely employed in nanomedicine and PDI plays a functional role in various diseases, the interactions between oxidized (oPDI) and reduced (rPDI) with 50 nm citrate-coated AuNPs (AuNPs) are examined in this study using various techniques. Upon incubation, PDI adsorbs to the AuNP surface, which leads to a reduction in its enzymatic activity despite limited changes in secondary structures. Partial enzymatic digestion followed by mass spectrometry analysis shows that orientation of PDI on the NP surface is dependent on both its oxidation state and the PDI:AuNP incubation ratios. 

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