Biomolecular Corona Research Articles

Navigating the nano-bio immune interface: advancements and challenges in CNS nanotherapeutics

In recent years, significant advancements have been made in utilizing nanoparticles (NPs) to modulate immune responses within the central nervous system (CNS), offering new opportunities for nanotherapeutic interventions in neurological disorders. NPs can serve as carriers for immunomodulatory agents or platforms for delivering nucleic acid-based therapeutics to regulate gene expression and modulate immune responses. Several studies have demonstrated the efficacy of NP-mediated immune modulation in preclinical models of neurological diseases, including multiple sclerosis, stroke, Alzheimer’s disease, and Parkinson’s disease. While challenges remain, advancements in NPs engineering and design have led to the development of NPs using diverse strategies to overcome these challenges. The nano-bio interface with the immune system is key in the conceptualization of NPs to efficiently act as nanotherapeutics in the CNS. The biomolecular corona plays a pivotal role in dictating NPs behavior and immune recognition within the CNS, giving researchers the opportunity to optimize NPs design and surface modifications to minimize immunogenicity and enhance biocompatibility. Here, we review how NPs interact with the CNS immune system, focusing on immunosurveillance of NPs, NP-induced immune reprogramming and the impact of the biomolecular corona on NPs behavior in CNS immune responses. The integration of NPs into CNS nanotherapeutics offers promising opportunities for addressing the complex challenges of acute and chronic neurological conditions and pathologies, also in the context of preventive and rehabilitative medicine. By harnessing the nano-bio immune interface and understanding the significance of the biomolecular corona, researchers can develop targeted, safe, and effective nanotherapeutic interventions for a wide range of CNS disorders to improve treatment and rehabilitation. These advancements have the potential to revolutionize the treatment landscape of neurological diseases, offering promising solutions for improved patient care and quality of life in the future.

Recent Updates on Diverse Nanoparticles and Nanostructures in Therapeutic and Diagnostic Applications with Special Focus on Smart Protein Nanoparticles: A Review.

Nanomedicine enables advanced therapeutics, diagnostics, and predictive analysis, enhancing treatment outcomes and patient care. The choices and development of high-quality organic nanoparticles with relatively lower toxicity are important for achieving advanced medical goals. Among organic molecules, proteins have been prospected as smart candidates to revolutionize nanomedicine due to their inherent fascinating features. The advent of protein nanoarchitectures, which explore the biomolecular corona, offers new insights into their efficient tissue penetration and therapeutic potential. This review examines various animal- and plant-based protein nanoparticles, highlighting their source, activity, products, and unique biomedical applications in regenerative medicine, targeted therapies, gene and drug delivery, antimicrobial activity, bioimaging, immunological adjuvants, etc. It provides an extensive discussion on recent applications of protein nanoparticles across diverse biomedical fields as well as the evolving landscape of other nanoproducts and nanodevices for sensitive medical procedures. Furthermore, this review introduces different preparation technologies of protein nanoparticles, emphasizing how their design and construction significantly influence loading capacity, stability, and targeting effects. Additionally, we delve into the construction of different user-friendly multifunctional modular bioarchitectures by the assembly of protein nanoparticles (PNPs), marking a significant breakthrough in therapies. This review also considers the challenges of synthetic nanomaterials and the emergence of natural alternatives, which provides insights into protein nanoparticle research.

Manipulating Silver Nanoparticles with Biomolecular Corona Secreted from Vertebrates to Improve the Loading Capacity and Biocompatibility.

Silver nanoparticles (AgNPs) are widely used as nanoagents in biomedical fields, while it is still challenging to improve their loading capacity and biocompatibility in microcarrier delivering systems. Herein, the physicochemical properties of AgNPs were manipulated by forming biomolecular corona derived from bovine serum albumin (AC), and three organisms at various trophic levels: Chlorella sp. (BC1), Daphnia magna (BC2), and zebrafish (BC3). Proteins were identified by chemical composition analysis as the dominant components adsorbed on the surface of AgNPs. Proteomics indicated that AgNPs preferred to bind with low molecular weight (<50 kDa) and hydrophobic proteins with more positively charged residues. Consequently, AC and BC3 displayed stronger adsorption affinity on the surface of AgNPs than BC1 and BC2. Modifications by AC and BC3 effectively alleviated the oxidative stress and cell cycle arrest of AgNPs due to their superior antioxidative ability. However, BC3 with lower hydrophobicity enabled AgNPs to be more biocompatible than AC at subcellular level. Moreover, AC could significantly improve the loading capacity of AgNPs by Chlorella through enhancing caveolin-mediated endocytosis. Notably, owing to the adsorption of abundant Ca2+-binding proteins, BC3-AgNPs could also be internalized by microalgae via Ca2+-dependent clathrin-mediated endocytosis, which makes it a promising approach to deliver AgNPs. The results of this study would provide insights into the development of an efficient strategy to deliver AgNPs based on the microalgae carrier without altering its original properties and functionality.

Adsorption of bile salts onto crystalline ritonavir particles under simulated gastrointestinal conditions

The formation of a biomolecular corona on nanoparticles in blood is a well-known phenomenon influencing in vivo performance. Analogous phenomena in other biological fluids, such as the formation of a gastrointestinal (GI) corona, remain under-investigated. The ingestion of medicines leads to the generation of drug particles in the GI fluids. Consequently, an understanding of the behavior of drug particles in the gut requires determination of the adsorption of bile components onto these drug particles. This work aims to elucidate the factors affecting adsorption of bile salts onto ritonavir (RTV) particles. Crystalline RTV particles were incubated with non-micellar or micellar bile salts and bile salt depletion from solution was measured using HPLC and small angle X-ray scattering (SAXS). HPLC results show that bile salts adsorb onto RTV particles, with greater adsorption observed for more hydrophobic bile salts, following the order sodium glycodeoxycholate (SGDC)>sodium taurodeoxycholate (STDC)>sodium glycochenodeoxycholate SGCDC>sodium glycocholate (SGC)>sodium taurocholate (STC). Increasing the ionic strength of the solution led to increased adsorption of STDC, where buffer containing 300 mM NaCl resulted in greater adsorption than 150 mM NaCl. Additionally, micellar bile salts showed greater affinity for RTV particles than unimeric bile salts. In contrast, the extent of bile salt depletion was unaltered by addition of phospholipid to form mixed micelles. SAXS analysis of mixed micelles after incubation with RTV particles confirms depletion of bile salt from the supernatant, evidenced by reduced intensity of the micellar scattering feature. In conclusion, this study investigated factors influencing bile salt adsorption onto drug particles, highlighting the need to consider adsorption of bile components in forming the GI-corona.

Multifunctional biomolecular corona-inspired nanoremediation of antibiotic residues.

Facing complex and variable emerging antibiotic pollutants, the traditional development of functional materials is a "trial-and-error" process based on physicochemical principles, where laborious steps and long timescales make it difficult to accelerate technical breakthroughs. Notably, natural biomolecular coronas derived from highly tolerant organisms under significant contamination scenarios can be used in conjunction with nanotechnology to tackling emerging contaminants of concern. Here, super worms (Tubifex tubifex) with high pollutant tolerance were integrated with nano-zero valent iron (nZVI) to effectively reduce the content of 17 antibiotics in wastewater within 7 d. Inspired by the synergistic remediation, nZVI-augmented worms were constructed as biological nanocomposites. Neither nZVI (0.3 to 3 g/L) nor worms (104 to 105 per liter) alone efficiently degraded florfenicol (FF, as a representative antibiotic), while their composite removed 87% of FF (3 μmol/L). Under antibiotic exposure, biomolecules secreted by worms formed a corona on and modified the nZVI particle surface, enabling the nano-bio interface greater functionality, including responsiveness, enrichment, and reduction. Mechanistically, FF exposure activated glucose-alanine cycle pathways that synthesize organic acids and amines as major metabolites, which were assembled into vesicles and secreted, thereby interacting with nZVI in a biologically response design strategy. Lactic acid and urea formed hydrogen bonds with FF, enriched analyte presence at the heterogeneous interface. Succinic and lactic acids corroded the nZVI passivation layer and promoted electron transfer through surface conjugation. This unique strategy highlights biomolecular coronas as a complex resource to augment nano-enabled technologies and will provide shortcuts for rational manipulation of nanomaterial surfaces with coordinated multifunctionalities.

Biomimetic Plasmonic Nanophages by Head/Tail Self-Assembling: Gold Nanoparticle/Virus Interactions.

Gold nanoparticles (AuNPs), because of their dual plasmonic and catalytic functionalities, are among the most promising nanomaterials for the development of therapeutic and diagnostic tools for severe diseases such as cancer and neurodegeneration. Bacteriophages, massively present in human biofluids, are emerging as revolutionary biotechnological tools as they can be engineered to display multiple specific binding moieties, providing effective targeting ability, high stability, low cost, and sustainable production. Coupling AuNPs with phages can lead to an advanced generation of nanotools with great potential for biomedical applications. In the present study, we analyzed the interactions between differently sized AuNPs and filamentous M13 phages, establishing an advanced characterization platform that combines analytical techniques and computational models for an in-depth understanding of these hybrid self-assembling systems. A precise and structurally specific interaction of the AuNP-M13 hybrid complexes was observed, leading to a peculiar head/tail "tadpole-like" configuration. In silico simulations allowed explaining the mechanisms underlying the preferential assembly route and providing information about AuNPs' size-dependent interplay with specific M13 capsid proteins. The AuNP-M13 structures were proven to be biomimetic, eluding the formation of biomolecular corona. By keeping the biological identity of the virion, hybrid nanostructures maintained their natural recognition/targeting ability even in the presence of biomolecular crowding. In addition, we were able to tune the hybrid nanostructures' tropism toward E. coli based on the AuNP size. Overall, our results set the fundamental basis and a standard workflow for the development of phage-based targeting nanotools, valuable for a wide spectrum of nanotechnology applications.

Protocols for isolation and characterization of nanoparticle biomolecular corona complexes.

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.

Nanoparticle-assisted tubulin assembly is environment dependent

Nanomaterials acquire a biomolecular corona upon introduction to biological media, leading to biological transformations such as changes in protein function, unmasking of epitopes, and protein fibrilization. Ex vivo studies to investigate the effect of nanoparticles on protein-protein interactions are typically performed in buffer and are rarely measured quantitatively in live cells. Here, we measure the differential effect of silica nanoparticles on protein association in vitro vs. in mammalian cells. BtubA and BtubB are a pair of bacterial tubulin proteins identified in Prosthecobacter strains that self-assemble like eukaryotic tubulin, first into dimers and then into microtubules in vitro or in vivo. Förster resonance energy transfer labeling of each of the Btub monomers with a donor (mEGFP) and acceptor (mRuby3) fluorescent protein provides a quantitative tool to measure their binding interactions in the presence of unfunctionalized silica nanoparticles in buffer and in cells using fluorescence spectroscopy and microscopy. We show that silica nanoparticles enhance BtubAB dimerization in buffer due to protein corona formation. However, these nanoparticles have little effect on bacterial tubulin self-assembly in the complex mammalian cellular environment. Thus, the effect of nanomaterials on protein-protein interactions may not be readily translated from the test tube to the cell in the absence of particle surface functionalization that can enable targeted protein-nanoparticle interactions to withstand competitive binding in the nanoparticle corona from other biomolecules.

Unveiling the Power of Cloaking Metal-Organic Framework Platforms via Supramolecular Antibody Conjugation.

Targeted drug delivery systems based on metal-organic frameworks (MOFs) have progressed tremendously since inception and are now widely applicable in diverse scientific fields. However, translating MOF agents directly to targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we observed that supramolecular conjugation of antibodies to the surface of MOF particles (MOF-808) via electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments and show stealth shields. Once antibodies are stably conjugated to particles, they were neither easily exchanged with nor covered by biomolecule proteins, which is indicative of the stealth effect. Moreover, upon conjugation of the MOF particle with specific targeted antibodies, namely, anti-CD44, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR), the resulting hybrid exhibits an augmented targeting efficacy toward cancer cells overexpressing these receptors, such as HeLa, SK-BR-3, and 4T1, as evidenced by flow cytometry. The therapeutic effectiveness of the antibody-conjugated MOF (anti-M808) was further evaluated through in vivo imaging and the assessment of tumor inhibition effects using IR-780-loaded EGFR-M808 in a 4T1 tumor xenograft model employing nude mice. This study therefore provides insight into the use of supramolecular antibody conjugation as a promising method for developing MOF-based drug delivery systems.

A Review on Investigating the Interactions between Nanoparticles and the Pulmonary Surfactant Monolayer with Coarse-Grained Molecular Dynamics Method.

Pulmonary drug delivery has garnered significant attention due to its targeted local lung action, minimal toxic side effects, and high drug utilization. However, the physicochemical properties of inhaled nanoparticles (NPs) used as drug carriers can influence their interactions with the pulmonary surfactant (PS) monolayer, potentially altering the fate of the NPs and impairing the biophysical function of the PS monolayer. Thus, the objective of this review is to summarize how the physicochemical properties of NPs affect their interactions with the PS monolayer. Initially, the definition and properties of NPs, as well as the composition and characteristics of the PS monolayer, are introduced. Subsequently, the coarse-grained molecular dynamics (CGMD) simulation method for studying the interactions between NPs and the PS monolayer is presented. Finally, the implications of the hydrophobicity, size, shape, surface charge, surface modification, and aggregation of NPs on their interactions with the PS monolayer and on the composition of biomolecular corona are discussed. In conclusion, gaining a deeper understanding of the effects of the physicochemical properties of NPs on their interactions with the PS monolayer will contribute to the development of safer and more effective nanomedicines for pulmonary drug delivery.

Lipid nanoparticle-based strategies for extrahepatic delivery of nucleic acid therapies – challenges and opportunities

The advent of lipid nanoparticles (LNPs) containing ionizable cationic lipids has enabled the encapsulation, stabilization, and intracellular delivery of nucleic acid payloads, leading to FDA-approved siRNA-based therapy and mRNA-based vaccines. Other nucleic acid-based therapeutic modalities, including protein replacement and CRISPR-mediated gene knockout and editing, are being tested in clinical trials, in many cases, for the treatment of liver-related diseases. However, to fully exploit these therapies beyond the liver, improvements in their delivery to extrahepatic targets are needed. Towards this end, both active targeting strategies based on targeting ligands grafted onto LNPs and passive targeting relying on physicochemical LNP parameters such as surface composition, charge, and size are being evaluated. Often, the latter strategy depends on the interaction of LNPs with blood components, forming what is known as the biomolecular corona. Here, I discuss potential challenges related to current LNP-based targeting strategies and the studies of the biomolecular corona on LNPs. I propose potential solutions to overcome some of these obstacles and present approaches currently being tested in preclinical and clinical studies, which face fewer biological barriers than traditional organ-targeting approaches.

Deciphering the monocyte-targeting mechanisms of PEGylated cationic liposomes by investigating the biomolecular corona

Cationic liposomes specifically target monocytes in blood, rendering them promising drug-delivery tools for cancer immunotherapy, vaccines, and therapies for monocytic leukaemia. The mechanism behind this monocyte targeting ability is, however, not understood, but may involve plasma proteins adsorbed on the liposomal surfaces. To shed light on this, we investigated the biomolecular corona of three different types of PEGylated cationic liposomes, finding all of them to adsorb hyaluronan-associated proteins and proteoglycans upon incubation in human blood plasma. This prompted us to study the role of the TLR4 co-receptors CD44 and CD14, both involved in signalling and uptake pathways of proteoglycans and glycosaminoglycans. We found that separate inhibition of each of these receptors hampered the monocyte uptake of the liposomes in whole human blood. Based on clues from the biomolecular corona, we have thus identified two receptors involved in the targeting and uptake of cationic liposomes in monocytes, in turn suggesting that certain proteoglycans and glycosaminoglycans may serve as monocyte-targeting opsonins. This mechanistic knowledge may pave the way for rational design of future monocyte-targeting drug-delivery platforms.

Advancing In Situ Analysis of Biomolecular Corona: Opportunities and Challenges in Utilizing Field-Flow Fractionation.

The biomolecular corona, a complex layer of biological molecules, envelops nanoparticles (NPs) upon exposure to biological fluids including blood. This dynamic interface is pivotal for the advancement of nanomedicine, particularly in areas of therapy and diagnostics. In situ analysis of the biomolecular corona is crucial, as it can substantially improve our ability to accurately predict the biological fate of nanomedicine and, therefore, enable development of more effective, safe, and precisely targeted nanomedicines. Despite its importance, the repertoire of techniques available for in situ analysis of the biomolecular corona is surprisingly limited. This tutorial review provides an overview of the available techniques for in situ analysis of biomolecular corona with a particular focus on exploring both the advantages and the limitations inherent in the use of field-flow fractionation (FFF) for in situ analysis of the biomolecular corona. It delves into how FFF can unravel the complexities of the corona, enhancing our understanding and guiding the design of next-generation nanomedicines for medical use.

Stability and dispersibility of microplastics in experimental exposure medium and their dimensional characterization by SMLS, SAXS, Raman microscopy, and SEM

The plastic production that contributes to the global plastic reservoir presents a major challenge for society in managing plastic waste and mitigating the environmental damage of microplastic (MP) pollution. In the environment, the formation of biomolecular corona around MPs enhance the stability of MP suspensions, influencing the bioavailability and toxicity of MPs. Essential physical properties including MP stability, dispersibility, agglomeration, and dimensional size must be precisely defined and measured in complex media taking into account the formation of a protein corona. Using static multiple light scattering (SMLS), small angle X-ray scattering (SAXS), Raman microscopy, and scanning electron microscopy (SEM), we measured the particle size, density, stability, and agglomeration state of polyethylene and polypropylene MPs stabilized in aqueous suspension by BSA. SEM analysis revealed the formation of nanoplastic debris as MP suspensions aged. Our results suggest that protein adsorption favors the formation of secondary nanoplastics, potentially posing an additional threat to ecosystems. This approach provides analytical methodologies by integrating SEM, SMLS, and SAXS, for characterizing MP suspensions and highlights the effect of the protein corona on size measurements of micro/nanoplastics. Our analysis demonstrates the detectability of secondary nanoplastics by SEM, paving the way for monitoring and controlling human exposure.

A magnetic separation method for isolating and characterizing the biomolecular corona of lipid nanoparticles

Lipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids for gene therapy as exemplified by the worldwide rollout of LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still a major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components of which adsorb onto the LNP surface forming a layer of biomolecules termed the "biomolecular corona (BMC)" which affects LNP stability, biodistribution, and tissue tropism. The mechanisms by which the BMC influences tissue- and cell-specific targeting remains largely unknown, due to the technical challenges in isolating LNPs and their corona from complex biological media. In this study, we present a new technique that utilizes magnetic LNPs to isolate LNP-corona complexes from unbound proteins present in human serum. First, we developed a magnetic LNP formulation, containing >40 superparamagnetic iron oxide nanoparticles (IONPs)/LNP, the resulting LNPs containing iron oxide nanoparticles (IOLNPs) displayed a similar particle size and morphology as LNPs loaded with nucleic acids. We further demonstrated the isolation of the IOLNPs and their corresponding BMC from unbound proteins using a magnetic separation (MS) system. The BMC profile of LNP from the MS system was compared to size exclusion column chromatography and further analyzed via mass spectrometry, revealing differences in protein abundances. This new approach enabled a mild and versatile isolation of LNPs and its corona, while maintaining its structural integrity. The identification of the BMC associated with an intact LNP provides further insight into LNP interactions with biological fluids.

Impact of Whey Protein Corona Formation around TiO2 Nanoparticles on Their Physiochemical Properties and Gastrointestinal Fate.

Previously, we found that whey proteins form biomolecular coronas around titanium dioxide (TiO2) nanoparticles. Here, the gastrointestinal fate of whey protein-coated TiO2 nanoparticles and their interactions with gut microbiota were investigated. The antioxidant activity of protein-coated nanoparticles was enhanced after simulated digestion. The structure of the whey proteins was changed after they adsorbed to the surfaces of the TiO2 nanoparticles, which reduced their hydrolysis under simulated gastrointestinal conditions. The presence of protein coronas also regulated the impact of the TiO2 nanoparticles on colonic fermentation, including promoting the production of short-chain fatty acids. Bare TiO2 nanoparticles significantly increased the proportion of harmful bacteria and decreased the proportion of beneficial bacteria, but the presence of protein coronas alleviated this effect. In particular, the proportion of beneficial bacteria, such as Bacteroides and Bifidobacterium, was enhanced for the coated nanoparticles. Our results suggest that the formation of a whey protein corona around TiO2 nanoparticles may have beneficial effects on their behavior within the colon. This study provides valuable new insights into the potential impact of protein coronas on the gastrointestinal fate of inorganic nanoparticles.

Multiscale modelling of biomolecular corona formation on metallic surfaces.

In the realm of food industry, the choice of non-consumable materials used plays a crucial role in ensuring consumer safety and product quality. Aluminum is widely used in food packaging and food processing applications, including dairy products. However, the interaction between aluminum and milk content requires further investigation to understand its implications. In this work, we present the results of multiscale modelling of the interaction between various surfaces, that is (100), (110), and (111), of fcc aluminum with the most abundant milk proteins and lactose. Our approach combines atomistic molecular dynamics, a coarse-grained model of protein adsorption, and kinetic Monte Carlo simulations to predict the protein corona composition in the deposited milk layer on aluminum surfaces. We consider a simplified model of milk, which is composed of the six most abundant milk proteins found in natural cow milk and lactose, which is the most abundant sugar found in dairy. Through our study, we ranked selected proteins and lactose adsorption affinities based on their corresponding interaction strength with aluminum surfaces and predicted the content of the naturally forming biomolecular corona. Our comprehensive investigation sheds light on the implications of aluminum in food processing and packaging, particularly concerning its interaction with the most abundant milk proteins and lactose. By employing a multiscale modelling approach, we simulated the interaction between metallic aluminum surfaces and the proteins and lactose, considering different crystallographic orientations. The results of our study provide valuable insights into the mechanisms of lactose and protein deposition on aluminum surfaces, which can aid in the general understanding of protein corona formation.

Nano-Bio Interactions: Exploring the Biological Behavior and the Fate of Lipid-Based Gene Delivery Systems.

Gene therapy for many diseases is rapidly becoming a reality, as demonstrated by the recent approval of various nucleic acid-based therapeutics. Non-viral systems such as lipid-based carriers, lipid nanoparticles (LNPs), for delivering different payloads including small interfering RNA, plasmid DNA, and messenger RNA have been particularly extensively explored and developed for clinical uses. One of the most important issues in LNP development is delivery to extrahepatic tissues. To achieve this, various lipids and lipid-like materials are being examined and screened. Several LNP formulations that target extrahepatic tissues, such as the spleen and the lungs have been developed by adjusting the lipid compositions of LNPs. However, mechanistic details of how the characteristics of LNPs affect delivery efficiency remains unclear. The purpose of this review is to provide an overview of LNP-based nucleic acid delivery focusing on LNP components and their structures, as well as discussing biological factors, such as biomolecular corona and cellular responses related to the delivery efficiency.

Effect of ligand and shell densities on the surface structure of core-shell nanoparticles self-assembled from function-spacer-lipid constructs.

Biomolecular corona is the major obstacle to the clinical translation of nanomedicines. Since corona formation is governed by molecular interactions at the nano-bio interface, nanoparticle surface properties such as topography, charge and surface chemistry can be tuned to manipulate biomolecular corona formation. To this end, as the first step towards a deep understanding of the processes of corona formation, it is necessary to develop nanoparticles employing various biocompatible materials and characterize their surface structure and dynamics at the molecular level. In this work, we applied molecular dynamics simulation to study the surface structure of organic core-shell nanoparticles formed by the self-assembly of synthetic molecules composed of a DOPE lipid, a carboxymethylglycine spacer and biotin. Lipid moieties form the hydrophobic core, spacer motifs serve as a hydrophilic shell and biotin residues function as a targeting ligand. By mixing such function-spacer-lipid, spacer-lipid and lipid-only constructs at various molar ratios, densities of the ligand and spacer on the nanoparticle surface were modified. For convenient analysis of the structure and dynamics of all regions of the nanoparticle surface, we compiled topography maps based on atomic coordinates. It was shown that an increase in the density of the shell does not reduce exposure of the core, but increases shell average thickness. Biotin, due to its alkyl valeric acid chain and spacer flexibility, is localized primarily near the hydrophobic core and its partial presentation on the surface occurs only in nanoparticles with higher ligand densities. However, an increase in biotin density leads to its clustering. In turn, ligand clustering diminishes the stealth properties of the shell and targeting efficiency. Based on nanoparticle surface structures, we determined the optimal density of biotin. Experimental studies reported in the literature confirm these conclusions. We also suggest design tips to achieve the preferred biotin presentation. Simulation results are consistent with the synchrotron SAXS profile. We believe that such studies will contribute to a better understanding of nano-bio interactions towards the rational design of efficient drug delivery systems.

Extracellular vesicles of different cellular origin feature distinct biomolecular corona dynamics

Initially observed on synthetic nanoparticles, biomolecular corona existence and role in determining nanoparticle identity and function are now beginning to be acknowledged in biogenic nanoparticles, particularly in extracellular vesicles. We...