Understanding both the physicochemical and biological interactions of nanoparticles is mandatory for the biomedical application of nanomaterials. By binding proteins, nanoparticles acquire new surface identities in biological fluids, the protein corona. Various studies have revealed the dynamic structure and nano-bio interactions of the protein corona. The binding of proteins not only imparts new surface identities to nanoparticles in biological fluids but also significantly influences their bioactivity, stability, and targeting specificity. Interestingly, recent endeavors have been undertaken to harness the potential of the protein corona instead of evading its presence. Exploitation of this \'protein-nanoparticle alliance\' has significant potential to change the field of nanomedicine. Here, we present a thorough examination of the latest research on protein corona, encompassing its formation, dynamics, recent developments, and diverse bioapplications. Furthermore, we also aim to explore the interactions at the nano-bio interface, paving the way for innovative strategies to advance the application potential of the protein corona. By addressing challenges and promises in controlling protein corona formation, this review provides insights into the evolving landscape of the \'protein-nanoparticle alliance\' and highlights emerging.

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a \'Protein Corona\'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs.

Asymmetrical flow field-flow fractionation (AF4) has attracted considerable attention as a size-based separation technique, due to its mild separation conditions, broad working range (from approximately 103 to 109 Da molecular mass or from 1 nm to 1 μm particle diameter), and versatility. AF4 is primarily being used to measure particle size, polydispersity, and physical stability of various systems, such as (bio)-macromolecules and nanoparticles. In comparison with size-exclusion chromatography (packed column), AF4 (open channel) allows separation while preserving labile structures. Monitoring of interactions between different compounds and in very complex matrices is possible. Preservation of the structure and correlation of structural characteristics with activity and functionality can bolster the development of new therapeutic strategies for diseases and new materials with improved properties. In this review, a detailed overview is presented of developments in AF4 for interaction studies between various systems, such as protein-protein, polymer-polymer, nanoparticle-drug, and nanoparticle-protein. The prospects and obstacles for AF4, and other less-commonly used types of FFF, for studying interactions within complex and fragile systems are covered. Coupling AF4 to a variety of detection systems can greatly contribute to the understanding of the interaction/association processes and provide information on the interaction kinetics. This review is intended to provide comprehensive documentation on the types of information (structural, morphological, chemical) on molecular interactions that can be retrieved by AF4.

Dementia, in particular, is a defining feature of Alzheimer\'s and Parkinson\'s diseases. Because of the combination of motor and cognitive impairments, Parkinson\'s disease dementia (PDD) has a greater impact on affected people than Alzheimer\'s disease dementia (ADD) and others. If one family member develops dementia, the other members will suffer greatly in terms of social and occupational functioning. Currently, no relevant treatment is available based on an examination of the absolute pathophysiology of dementia. As a result, our objective of current review encouraged to look for dementia pharmacotherapy based on their pathogenesis. We systematically searched electronic databases such as PubMed, Scopus, and ESCI for information on the pathophysiology of demetia, as well as their treatment with allopathic and herbal medications. By modulating intermediate proteins, oxidative stress, viral protein corona, and MMP9 are etiological factors that cause dementia. The pathophysiology of ADD was described by two hypotheses: the amyloid cascade hypothesis and the tau and tangle hypothesis. ADD is caused by an increase in amyloid-beta (Aβ) and neurofibrillary tangles in the cerebrum. The viral protein corona (VPC) is more contagious and helps to form amyloid-beta (Aβ) plaques and neurofibrillary tangles in the cerebrum. Thioredoxin interacting protein (TXNIP) inside the BBB encourages Aβ to become more engaged. PDD is caused by decreased or absent dopamine secretion from nerve cells in the substantia nigra, as well as PRKN gene deletion/duplication mutations, and shift in the PRKN-PACRG organisation, all of which are linked to ageing. This article discussed the pathophysiology of dementia, as well as a list of herbal medications that can easily cross the BBB and have a therapeutic effect on dementia.

Nanoparticles (NPs) are promising platforms for the development of diagnostic and therapeutic tools. One of the main hurdle to their medical application and translation into the clinic is the fact that they accumulate in the spleen and liver due to opsonization and scavenging by the mononuclear phagocyte system. The \"protein corona\" controls the fate of NPs in vivo and becomes the interface with cells, influencing their physiological response like cellular uptake and targeting efficiency. For these reasons, the surface properties play a pivotal role in fouling and antifouling behavior of particles. Therefore, surface engineering of the nanocarriers is an extremely important issue for the design of useful diagnostic and therapeutic systems. In recent decades, a huge number of studies have proposed and developed different strategies to improve antifouling features and produce NPs as safe and performing as possible. However, it is not always easy to compare the various approaches and understand their advantages and disadvantages in terms of interaction with biological systems. Here, we propose a systematic study of literature with the aim of summarizing current knowledge on promising antifouling coatings to render NPs more biocompatible and performing for diagnostic and therapeutic purposes. Thirty-nine studies from 2009 were included and investigated. Our findings have shown that two main classes of non-fouling materials (i.e., pegylated and zwitterionic) are associated with NPs and their applications are discussed here highlighting pitfalls and challenges to develop biocompatible tools for diagnostic and therapeutic uses. In conclusion, although the complexity of biofouling strategies and the field is still young, the collective data selected in this review indicate that a careful tuning of surface moieties is a pivotal step to lead NPs through their future clinical applications.

Since the interest in the biomedical applications of inorganic nanoparticles (NPs) has rapidly grown over the last decades, there is a need for a thorough characterization of bio-nano interactions. NPs introduced to the body (mostly intravenously) encounter plasma proteins, that instantly create a so-called \"protein corona\" on the NPs surface, giving the nanomaterial a new biological identity. Type of the proteins that interact with NPs may affect the in vivo fate of NPs. For that reason, it is particularly important to establish analytical methods capable of corona protein identification. Bottom-up proteomics is most often used for that purpose. A crucial part of the experiment is sample preparation, as it is already proven that different protocols may lead to distinct results. This review is aimed at providing a characterization of two main stages of sample preparation: separation of NPs with protein corona from the unbound proteins and the digestion of corona proteins. Separation techniques such as centrifugation, magnetic separation, and chromatography and three digestion methods (in-gel, in-solution, and on-particle) are described with special emphasis paid on their advantages and disadvantages as well as their influence on the result of identification. This paper also indicates the need for standardization of protein corona identification protocols, as some of the proteins may be preferentially detected while applying a particular digestion procedure.

Proteins are biopolymers of highly varied structures taking part in almost all processes occurring in living cells. When nanoparticles (NPs) interact with proteins in biological environments, they are surrounded by a layer of biomolecules, mainly proteins adsorbing to the surfaces. This protein rich layer formed around NPs is called the \"protein corona\". Consequential interactions between NPs and proteins are governed due to the characteristics of the corona. The features of NPs such as the size, surface chemistry, charge are the critical factors influencing the behavior of protein corona. Molecular properties and protein corona composition affect the cellular uptake of NPs. Understanding and analyzing protein corona formation in relation to protein-NP properties, and elucidating its biological implications play an important role in bio-related nano-research studies. Protein-NP interactions have been studied extensively for the purpose of investigating the potential use of NPs as carriers in drug delivery systems. Further study should focus on exploring the effects of various characteristic parameters, such as the particle size, modifier type, temperature, pH on protein-NP interactions, providing toxicity information of novel NPs. In this contribution, important aspects related to protein corona forming, influential factors, novel findings and future perspectives on protein-NP interactions are overviewed.

Upon entering into the biological environments, the surface of the nanoparticles is immediately coated with proteins and form the so-called a protein corona due to which a nanoparticle changes its \"synthetic\" identity to a new \"biological\" identity. Different types of nanoparticles have different protein binding profiles, which is why they have different protein corona composition and therefore it cannot be said that there is a universal protein corona. The composition and amount of protein in the corona depends on the physical and chemical characteristics of the nanoparticles, the type of biological medium and the exposure time. Protein corona increases the diameter but also changes the composition of the surface of the nanoparticles and these changes affect biodistribution, efficacy, and toxicity of the nanoparticles.

Recent years have witnessed unprecedented increase in the use of nanoparticles in various sectors viz. electronics, catalysis, agriculture, textile, cosmetics, bio-medicine, packaging, house-holds and food-associated consumer products. This has led to the inevitable release of nanoparticles into the environment, which can have negative impact on living beings. Humans can also be exposed to these nanoparticles either intentionally or accidently. Nanoparticles can enter in the human body through food chain, inhalation, open wounds, drugs and intravenous injections etc. In majority of these cases, the nanoparticles may pass through the various cell layers, cell sap and finally enter into the blood. Upon interaction with biological fluid, nanoparticles come in close proximity particularly to the proteins present in the fluid. The assembly of proteins surrounding the nanoparticle\'s surface is called as protein corona and their complex is known as protein-nanoparticle complex. Formation of protein corona is a vibrant and driving process, which plays a pivotal role in the functioning of nanoparticles in biological systems. Moreover, due to interaction of proteins with nanoparticles, conformational changes may occur in the native structure of protein, which may lead to change in the functioning of proteins towards its cellular interaction. The present review provides in-depth knowledge about the formation of protein corona around nanoparticles and the factors regulating this process. Further, it discusses various techniques that can be used for the protein corona analysis and obtaining information about molecular consequences upon nanoparticle\'s exposure. Finally, the functional aspects of protein-nanoparticle complex have been discussed in detail. In-depth understanding of protein-nanoparticles complex can be instrumental to generate well-suited nanoparticles with desired surface characteristics in the way to biological application.

Within the last two decades, the field of nanomedicine has not developed as successfully as has widely been hoped for. The main reason for this is the immense complexity of the biological systems, including the physico-chemical properties of the biological fluids as well as the biochemistry and the physiology of living systems. The nanoparticles\' physicochemical properties are also highly important. These differ profoundly from those of freshly synthesized particles when applied in biological/living systems as recent research in this field reveals. The physico-chemical properties of nanoparticles are predefined by their structural and functional design (core and coating material) and are highly affected by their interaction with the environment (temperature, pH, salt, proteins, cells). Since the coating material is the first part of the particle to come in contact with the environment, it does not only provide biocompatibility, but also defines the behavior (e.g. colloidal stability) and the fate (degradation, excretion, accumulation) of nanoparticles in the living systems. Hence, the coating matters, particularly for a nanoparticle system for biomedical applications, which has to fulfill its task in the complex environment of biological fluids, cells and organisms. In this review, we evaluate the performance of different coating materials for nanoparticles concerning their ability to provide colloidal stability in biological media and living systems.