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.
more »
« less
Nanoparticle protein corona: from structure and function to therapeutic targeting
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.
more »
« less
- Award ID(s):
- 2145491
- NSF-PAR ID:
- 10436328
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 23
- Issue:
- 6
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 1432 to 1466
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
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 for
in situ analysis 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. -
more » « less
Abstract Controlling nanocarrier interactions with the immune system requires a thorough understanding of the surface properties that modulate protein adsorption in biological fluids, since the resulting protein corona redefines cellular interactions with nanocarrier surfaces. Albumin is initially one of the dominant proteins to adsorb to nanocarrier surfaces, a process that is considered benign or beneficial by minimizing opsonization or inflammation. Here, we demonstrate the surface chemistry of a model nanocarrier can be engineered to stabilize or denature the three-dimensional conformation of adsorbed albumin, which respectively promotes evasion or non-specific clearance in vivo. Interestingly, certain common chemistries that have long been considered to convey stealth properties denature albumin to promote nanocarrier recognition by macrophage class A1 scavenger receptors, providing a means for their eventual removal from systemic circulation. We establish that the surface chemistry of nanocarriers can be specified to modulate adsorbed albumin structure and thereby tune clearance by macrophage scavenger receptors.
-
Protein adsorption on surfaces greatly impacts many applications such as biomedical materials, anti-biofouling coatings, bio-separation membranes, biosensors, antibody protein drugs etc. For example, protein drug adsorption on the widely used lubricant silicone oil surface may induce protein aggregation and thus affect the protein drug efficacy. It is therefore important to investigate the molecular behavior of proteins at the silicone oil/solution interface. Such an interfacial study is challenging because the targeted interface is buried. By using sum frequency generation vibrational spectroscopy (SFG) with Hamiltonian local mode approximation method analysis, we studied protein adsorption at the silicone oil/protein solution interface in situ in real time, using bovine serum albumin (BSA) as a model. The results showed that the interface was mainly covered by BSA dimers. The deduced BSA dimer orientation on the silicone oil surface from the SFG study can be explained by the surface distribution of certain amino acids. To confirm the BSA dimer adsorption, we treated adsorbed BSA dimer molecules with dithiothreitol (DTT) to dissociate these dimers. SFG studies on adsorbed BSA after the DTT treatment indicated that the silicone oil surface is covered by BSA dimers and BSA monomers in an approximate 6 : 4 ratio. That is to say, about 25% of the adsorbed BSA dimers were converted to monomers after the DTT treatment. Extensive research has been reported in the literature to determine adsorbed protein dimer formation using ex situ experiments, e.g. , by washing off the adsorbed proteins from the surface then analyzing the washed-off proteins, which may induce substantial errors in the washing process. Dimerization is a crucial initial step for protein aggregation. This research developed a new methodology to investigate protein aggregation at a solid/liquid (or liquid/liquid) interface in situ in real time using BSA dimer as an example, which will greatly impact many research fields and applications involving interfacial biological molecules.more » « less
-
more » « less
Abstract In this Review, an effort is made to discuss the most recent progress and future trend in the two‐way traffic of the interactions between plants and nanoparticles (NPs). One way is the use of plants to synthesize NPs in an environmentally benign manner with a focus on the mechanism and optimization of the synthesis. Another way is the effects of synthetic NPs on plant fate with a focus on the transport mechanisms of NPs within plants as well as NP‐mediated seed germination and plant development. When NPs are in soil, they can be adsorbed at the root surface, followed by their uptake and inter/intracellular movement in the plant tissues. NPs may also be taken up by foliage under aerial deposition, largely through stomata, trichomes, and cuticles, but the exact mode of NP entry into plants is not well documented. The NP–plant interactions may lead to inhibitory or stimulatory effects on seed germination and plant development, depending on NP compositions, concentrations, and plant species. In numerous cases, radiation‐absorbing efficiency, CO2assimilation capacity, and delay of chloroplast aging have been reported in the plant response to NP treatments, although the mechanisms involved in these processes remain to be studied.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D2LC00799A
