Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition.

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.

Development of a fast and simple method for the isolation of superparamagnetic iron oxide nanoparticles protein corona from protein-rich matrices.

The adsorption of proteins onto the surface of nanoparticle (NP) leads to the formation of the so-called "protein corona" as consisting both loosely and tightly bound proteins. It is well established that the biological identity of NPs that may be acquired after exposure to a biological matrix is mostly provided by the components of the hard corona as the pristine surface is generally less accessible for binding. For that reason, the isolation and the characterisation of the NP-corona complexes and identification of the associated biomolecules can help in understanding its biological behaviour. Established methods for the isolation of the NP-HC complexes are time-demanding and can lead to different results based on the isolation method applied. Herein, we have developed a fast and simple method using ferromagnetic beads isolated from commercial MACS column and used for the isolation of superparamagnetic NP following exposure to different types of biological milieu. We first demonstrated the ability to easily isolate superparamagnetic iron oxide NPs (IONPs) from different concentrations of human blood plasma, and also tested the method on the corona isolation using more complex biological matrices, such as culture medium containing pulmonary mucus where the ordinary corona methods cannot be applied. Our developed method showed less than 20% difference in plasma corona composition when compared with centrifugation. It also showed effective isolation of NP-HC complexes from mucus-containing culture media upon comparing with centrifugation and MACS columns, which failed to wash out the unbound proteins. Our study was supported with a full characterisation profile including dynamic light scattering, nanoparticle tracking analysis, analytical disk centrifuge, and zeta potentials. The biomolecules/ proteins composing the HC were separated by vertical gel electrophoresis and subsequently analysed by liquid chromatography-tandem mass spectrometry. In addition to our achievements in comparing different isolation methods to separate IONPs with corona from human plasma, this is the first study that provides a complete characterisation profile of particle protein corona after exposure in vitro to pulmonary mucus-containing culture media.

Effect of the Protein Corona Formation on Antibody Functionalized Liquid Lipid Nanocarriers.

The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier by coupling a specific fluorescent antibody on the surface of functionalized lipid liquid nanocapsules (LLNCs). Thus, an anti-HER2-FITC antibody (αHER2) has been used, HER2 being a surface receptor that is overexpressed in several tumor cells. Subsequently, the in vitro formation of a PC has been developed using fetal bovine serum supplemented with human fibrinogen. Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Laser Doppler Electrophoresis (LDE), and Gel Chromatography techniques have been used to assure a complete physico-chemical characterization of the nano-complexes with (LLNCs-αHER2-PC) and without (LLNCs-αHER2) the surrounding PC. In addition, cellular assays were performed to study the cellular uptake and the specific cellular-nanocarrier interactions using the SKBR3 (high expression of HER2) breast cancer cell line and human dermal fibroblasts (HDFa) (healthy cell line without expression of HER2 receptors as control), showing that the SKBR3 cell line had a higher transport rate (50-fold) than HDFa at 60 min with LLNCs-αHER2. Moreover, the SKBR3 cell line incubated with LLNCs-αHER2-PC suffered a significant reduction (40%) in the uptake. These results suggest that the formation of a PC onto LLNCs does not prevent specific cell targeting, although it does have an important influence on cell uptake.

Differential cellular responses to FDA-approved nanomedicines: an exploration of albumin-based nanocarriers and liposomes in protein corona formation.

Albumin nanoparticles (NPs) and PEGylated liposomes have garnered tremendous interest as therapeutic drug carriers due to their unique physicochemical properties. These unique properties also have significant effects on the composition and structure of the protein corona formed around these NPs in a biological environment. Herein, protein corona formation on albumin NPs and liposomes was simultaneously evaluated through in vitro and simulation studies. The sizes of both types of NPs increased with more negatively charged interfaces upon being introduced into fetal bovine serum. Gel electrophoresis and label-free quantitative proteomics were performed to identify proteins recruited to the hard corona, and fewer proteins were found in albumin NPs than in liposomes, which is in accordance with isothermal titration calorimetry. The cellular uptake efficiency of the two NPs significantly differed in different serum concentrations, which was further scrutinized by loading an anticancer compound into albumin NPs. The presence of the hard protein corona increased the cellular uptake of albumin NPs in comparison with liposomes. In our simulation study, a specific receptor present in the membrane was greatly attracted to the albumin-apolipoprotein E complex. Overall, this study not only evaluated protein corona formation on albumin NPs, but also made promising advancements toward albumin- and liposome-based therapeutic systems.

Towards a simple in vitro surface chemistry pre-screening method for nanoparticles to be used for drug delivery to solid tumours.

An efficient nanoparticulate drug carrier intended for chemotherapy based on intravenous administration must exhibit a long enough blood circulation time, a good penetrability into the tumour volume, as well as an efficient uptake by cancer cells. Limiting factors for the therapeutic outcome in vivo are recognition of the nanoparticles as foreign objects, which triggers nanoparticle uptake by defence organs rich in macrophages, e.g. liver and spleen, on the time-scale of accumulation and uptake in/by the tumour. However, the development of nanomedicine towards efficient nanoparticle-based delivery to solid tumours is hampered by the lack of simple, reproducible, cheap, and predictive means for early identification of promising nanoparticle formulations. The surface chemistry of nanoparticles is known to be the most important determinant for the biological fate of nanoparticles, as it influences the extent of serum protein adsorption, and also the relative composition of the protein corona. Here we preliminarily evaluate an extremely simple screening method for nanoparticle surface chemistry pre-optimization based on nanoparticle uptake in vitro by PC-3 cancer cells and THP-1 macrophages. Only when both selectivity for the cancer cells as well as the extent of nanoparticle uptake are taken into consideration do the in vitro results mirror literature results obtained for small animal models. Furthermore, although not investigated here, the screening method does also lend itself to the study of actively targeted nanoparticles.

An In Situ Investigation of the Protein Corona Formation Kinetics of Single Nanomedicine Carriers by Self-Regulated Electrochemiluminescence Microscopy.

Protein coronas are present extensively at the bio-nano interface due to the natural adsorption of proteins onto nanomaterials in biological fluids. Aside from the robust property of nanoparticles, the dynamics of the protein corona shell largely define their chemical identity by altering interface properties. However, the soft coronas are normally complex and rapidly changing. To real-time monitor the entire formation, we report here a self-regulated electrochemiluminescence (ECL) microscopy based on the interaction of the Ru(bpy)3 3+ with the nanoparticle surface. Thus, the heterogeneity of the protein corona is in situ observed in single nanoparticle "cores" before and after loading drugs in nanomedicine carriers. The label-free, optical stable and dynamic ECL microscopy minimize misinterpretations caused by the variation of nanoparticle size and polydispersity. Accordingly, the synergetic actions of proteins and nanoparticles properties are uncovered by chemically engineered protein corona. After comparing the protein corona formation kinetics in different complex systems and different nanomedicine carriers, the universality and accuracy of this technique were well demonstrated via the protein corona formation kinetics curves regulated by competitive adsorption of Ru(bpy)3 3+ and multiple proteins on surface of various carriers. The work is of great significance for studying bio-nano interface in drug delivery and targeted cancer treatment.

Significance and implications of nanoparticle-biological corona fingerprints in diagnosis, prognosis, and therapeutics for diverse disorders.

Upon entering a biological environment, the surface of nanoparticles (NPs) is rapidly coated by various biomolecules (typically proteins), herein referred to as the biological corona fingerprint, representing a rich source of biological information that can guide the development of diagnosis, prognosis, and therapeutics for diverse disorders. Although the number of studies has been increasing and considerable technological success has been achieved over the past few years, the main obstacles in this field stem from the complexities and heterogeneity of disease biology due to an incomplete understanding of nano-bio interactions and the challenges regarding the chemistry, manufacturing, and controls required for clinical translation. This minireview highlights the progress, challenges, and opportunities in nano-biological corona fingerprinting for diagnosis, prognosis, and therapeutics, and offers suggestions for more effective nano-therapeutics by capitalizing on our growing understanding of tumor biology and nano-bio interactions. Encouragingly, the current understanding of biological fingerprints could favor the development of optimal delivery systems that use the NP-biological interaction rationale and computational analyses to guide more desirable nanomedicine designs and delivery strategies.

The interaction mechanism of plasma iron transport protein transferrin with nanoparticles.

In the biological systems, exposure to nanoparticles (NPs) can cause complicated interactions with proteins, the formation of protein corona and structural changes to proteins. These changes depend not only on NP physicochemical properties, but also on the intrinsic stability of protein molecules. Although, the formation of protein corona on the surface of NPs and the underlying mechanisms have been fully explored in various studies, no comprehensive review has discussed the direct biochemical and biophysical interactions between NPs and blood proteins, particularly transferrin. In this review, we first discussed the interaction of NPs with proteins to comprehend the effects of physicochemical properties of NPs on protein structure. We then overviewed the transferrin structure and its direct interaction with NPs to explore transferrin stability and its iron ion (Fe3+) release behavior. Afterwards, we surveyed the various biological functions of transferrin, such as Fe3+ binding, receptor binding, antibacterial activity, growth, differentiation, and coagulation, followed by the application of transferrin-modified NPs in the development of drug delivery systems for cancer therapy. We believe that this study can provide useful insight into the design and development of bioconjugates containing NP-transferrin for potential biomedical applications.

Protein adsorption determines pulmonary cell uptake of lipid-based nanoparticles.

The inhalable administration of lipid nanoparticles is an effective strategy for localised delivery of therapeutics against various lung diseases. Of this, improved intracellular delivery of pharmaceuticals for infectious disease and cancer management is of high significance. However, the influence of lipid nanoparticle composition and structure on uptake in pulmonary cell lines, especially in the presence of biologically relevant media is poorly understood. Here, the uptake of lamellar (liposomes) versus non-lamellar (cubosomes) lipid nanoparticles in macrophages and lung epithelial cells was quantified and the influence of bronchoalveolar lavage fluid (BALF), containing native pulmonary protein and surfactant molecules is determined. Cubosome uptake in both macrophages and epithelial cells was strongly mediated by a high percentage of molecular function regulatory and binding proteins present within the protein corona. In contrast, the protein corona did not influence the uptake of liposomes in epithelial cells. In macrophages, the proteins mediated a rapid internalisation, followed by exocytosis of liposomes after 6 h incubation. These findings on the influence of biological fluid in regulating lipid nanoparticle uptake mechanisms may guide future development of optimal intracellular delivery systems for therapeutics via the pulmonary route.

Role of the Protein Corona in the Colloidal Behavior of Microplastics.

Microparticles of polyethylene and polypropylene are largely found in aquatic environments because they are the most produced and persistent plastic materials. Once in biological media, they are covered by a layer of molecules, the so-called corona, mostly composed of proteins. A yeast protein extract from Saccharomyces cerevisiae was used as a protein system to observe interactions in complex biological media. Proteins, acting as surfactants and providing hydrophilic surfaces, allow the dispersion of highly hydrophobic particles in water and stabilize them. After 24 h, the microplastic quantity was up to 1 × 1011 particles per liter, whereas without protein, no particles remained in solution. Label-free imaging of the protein corona by synchrotron radiation deep UV fluorescence microscopy (SR-DUV) was performed. In situ images of the protein corona were obtained, and the adsorbed protein quantity, the coverage rate, and the corona heterogeneity were determined. The stability kinetics of the microplastic suspensions were measured by light transmission using a Turbiscan analyzer. Together, the microscopic and kinetics results demonstrate that the protein corona can very efficiently stabilize microplastics in solution provided that the protein corona quality is sufficient. Microplastic stability depends on different parameters such as the particle's intrinsic properties (size, density, hydrophobicity) and the protein corona formation that changes the particle wettability, electrostatic charge, and steric hindrance. By controlling these parameters with proteins, it becomes possible to keep microplastics in and out of solution, paving the way for applications in the field of microplastic pollution control and remediation.

Thermo-sensitive amylase-starch double-layer polymer nanoparticles with self-polishing and protein corona-free property for drug delivery applications.

Protein corona formation can lead to obstructive screening of targeting groups of nanoparticles (NPs). Also, the targeting groups are subjected to physiochemical interactions when exposed to solvents. Here, these two factors can influence NP targeting efficiency. Therefore, it is necessary to prepare a general method of preparing an anti-fouling NPs with protected targeting groups. Here, we designed α-amylase-starch double-layer coated poly (methyl methacrylate-co-acrylic acid) NPs (α-ams-SCMMA NPs), functionalized with aptamer targeting groups and doped with Tetrakis(para-hydraoxylphenyl) porphyrin (TPPOH) as a payload drug. Natural polysaccharide starch and enzyme α-amylase were applied here for thermo-sensitive activation of starch hydrolyzation in order to render the NPs' self-polishing from protein corona effects. During incubation with serum media, the protein corona was formed at the exterior shell of NPs, while the self-polishing process was activated to remove the "protein fouling" when the incubation temperature increased to 37 °C (body temperature). Mechanistically, the starch layer of α-ams-SCMMA NPs was readily hydrolysed by α-amylase, whereby the adsorbed protein corona could be efficiently eliminated and the targeting groups were then presented. With this unique self-polishing NP design, we believe our method can be applied for potential NP applications in cancer therepy due to excellent antifouling property and protected targeting groups.

The effects of serum albumin pre-adsorption of nanoparticles on protein corona and membrane interaction: A molecular simulation study.

As a platform to deliver imaging and therapeutic agents to targeted sites in vivo, nanoparticles (NPs) have widespread applications in diagnosis and treatment of cancer. However, the poor in vivo delivery efficiency of nanoparticles limits its potential for further application. Once enter the physiological environment, nanoparticles immediately interact with proteins and form protein corona, which changes the physicochemical properties of nanoparticle surface and further affects their transport. In this study, we performed molecular dynamics simulations to study the adsorption mechanism of nanoparticles with various surface modifications and different proteins (e.g., human serum albumin, complement protein C3b), and their interactions with cell membrane. The results show that protein human serum albumin prefers to interact with hydrophobic and positively charged nanoparticles, while the protein C3b prefers the hydrophobic and charged nanoparticles. The pre-adsorption of human serum albumin on the nanoparticle surface obviously decreases the interaction of nanoparticle with C3b. Furthermore, the high amount of protein pre-adsorption could decrease the probability of nanoparticle-membrane interaction. These results indicate that appropriate modification of nanoparticles with protein provides nanoparticles with better capability of targeting, which could be used to guide nanoparticle design and improve transport efficiency.

Tailor-Made Protein Corona Formation on Polystyrene Microparticles and its Effect on Epithelial Cell Uptake.

Microplastic particles are pollutants in the environment with a potential impact on ecology and human health. As soon as microplastic particles get in contact with complex (biological) environments, they will be covered by an eco- and/or protein corona. In this contribution, protein corona formation was conducted under defined laboratory conditions on polystyrene (PS) microparticles to investigate the influence on surface properties, protein corona evolution, particle-cell interactions, and uptake in two murine epithelial cells. To direct protein corona formation, PS particles were preincubated with five model proteins, namely, bovine serum albumin (BSA), myoglobin, ß-lactoglobulin, lysozyme, and fibrinogen. Subsequently, the single-protein-coated particles were incubated in a cell culture medium containing a cocktail of serum proteins to analyze changes in the protein corona profile as well as in the binding kinetics of the model proteins. Therein, we could show that the precoating step has a critical impact on the final composition of the protein corona. Yet, since proteins building the primary corona were still detectable after additional incubations in a protein-containing medium, backtracking of the particle's history is possible. Interestingly, whereas the precoating history significantly disturbs particle-cell interactions (PCIs), the cellular response (i.e., metabolic activity, MTT assay) stays unaffected. Of note, lysozyme precoating revealed one of the highest rates in PCI for both epithelial cell lines. Taken together, we could show that particle history has a significant impact on protein corona formation and subsequently on the interaction of particles with murine intestinal epithelial-like cells. However, as this study was limited to one cell type, further work is needed to assess if these observations can be generalized to other cell types.

Protein-corona formation on aluminum doped zinc oxide and gallium nitride nanoparticles.

The interaction of semiconductor nanoparticles with bio-molecules attracts increasing interest of researchers, considering the reactivity of nanoparticles and the possibility to control their properties remotely giving mechanical, thermal, or electrical stimulus to the surrounding bio-environment. This work reports on a systematic comparative study of the protein-corona formation on aluminum doped zinc oxide and gallium nitride nanoparticles. Bovine serum albumin was chosen as a protein model. Dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy techniques have been used to demonstrate the formation of protein-corona as well as the stability of the colloidal suspension given by BSA, which also works as a surfactant. The protein adsorption on the NPs surface studied by Bradford Assay showed the dependence on the quantity of proteins adsorbed to the available sites on the NPs surface, thus the saturation was observed at ratio higher than 5:1 (NPs:Proteins) in case of ZnO, these correlating with DLS results. Moreover, the kinetics of the proteins showed a relatively fast adsorption on the NPs surface with a saturation curve after about 25 min. GaN NPs, however, showed a very small amount of proteins adsorbed on the surface, a change in the hydrodynamic size being not observable with DLS technique or differential centrifugal sedimentation. The Circular Dichroism analysis suggests a drastic structural change in the secondary structure of the BSA after attaching on the NPs surface. The ZnO nanoparticles adsorb a protein-corona, which does not protect them against dissolution, and in consequence, the material proved to be highly toxic for Human keratinocyte cell line (HaCaT) at concentration above 25 µg/mL. In contrast, the GaN nanoparticles which do not adsorb a protein-corona, show no toxicity signs for HaCaT cells at concentration as high as 50 µg/mL, exhibiting much lower concentration of ions leakage in the culture medium as compared to ZnO nanoparticles.

Trident Nano-Indexing the Proteomics Table: Next-Version Clustering of Iron Carbide NPs and Protein Corona.

Protein corona composition and precise physiological understanding of differentially expressed proteins are key for identifying disease biomarkers. In this report, we presented a distinctive quantitative proteomics table of molecular cell signaling differentially expressed proteins of corona that formed on iron carbide nanoparticles (NPs). High-performance liquid chromatography/electrospray ionization coupled with ion trap mass analyzer (HPLC/ESI-Orbitrap) and MASCOT helped quantify 142 differentially expressed proteins. Among these proteins, 104 proteins showed upregulated behavior and 38 proteins were downregulated with respect to the control, whereas 48, 32 and 24 proteins were upregulated and 8, 9 and 21 were downregulated CW (control with unmodified NPs), CY (control with modified NPs) and WY (modified and unmodified NPs), respectively. These proteins were further categorized on behalf of their regularity, locality, molecular functionality and molecular masses using gene ontology (GO). A STRING analysis was used to target the specific range of proteins involved in metabolic pathways and molecular processing in different kinds of binding functionalities, such as RNA, DNA, ATP, ADP, GTP, GDP and calcium ion bindings. Thus, this study will help develop efficient protocols for the identification of latent biomarkers in early disease detection using protein fingerprints.

Gold Nanoparticles Contact with Cancer Cell: A Brief Update.

The fine-tuning of the physicochemical properties of gold nanoparticles has facilitated the rapid development of multifunctional gold-based nanomaterials with diagnostic, therapeutic, and therapeutic applications. Work on gold nanoparticles is increasingly focusing on their cancer application. This review provides a summary of the main biological effects exerted by gold nanoparticles on cancer cells and highlights some critical factors involved in the interaction process (protein corona, tumor microenvironment, surface functionalization). The review also contains a brief discussion of the application of gold nanoparticles in target discovery.

Effect of dopamine-functionalization, charge and pH on protein corona formation around TiO2 nanoparticles.

Inorganic nanoparticles (NPs) are gaining increasing attention in nanomedicine because of their stimuli responsiveness, which allows combining therapy with diagnosis. However, little information is known about their interaction with intracellular or plasma proteins when they are introduced in a biological environment. Here we present atomistic molecular dynamics (MD) simulations investigating the case study of dopamine-functionalized TiO2 nanoparticles and two proteins that are overexpressed in cancer cells, i.e. PARP1 and HSP90, since experiments proved them to be the main components of the corona in cell cultures. The mechanism and the nature of the interaction (electrostatic, van der Waals, H-bonds, etc.) is unravelled by defining the protein residues that are more frequently in contact with the NPs, the extent of contact surface area and the variations in the protein secondary structures, at different pH and ionic strength conditions of the solution where they are immersed to simulate a realistic biological environment. The effects of the NP surface functionalization and charge are also considered. Our MD results suggest that less acidic intracellular pH conditions in the presence of cytosolic ionic strength enhance PARP1 interaction with the nanoparticle, whereas the HSP90 contribution is partly weakened, providing a rational explanation to existing experimental observations.

Isolation Methods Influence the Protein Corona Composition on Gold-Coated Iron Oxide Nanoparticles.

Upon exposure to a biological environment, nanoparticles (NPs) acquire biomolecular coatings, the most studied of which is the protein corona. This protein corona gives NPs a new biological identity that will determine various biological responses including cellular uptake, biodistribution, and toxicity. The standard method to isolate NPs from a biological matrix in order to study their coronas is centrifugation, but more gentle means of retrieval may enable deeper understanding of both irreversibly bound hard coronas and more loosely bound soft coronas. In this study, magnetic gold-coated iron oxide NPs were incubated with rainbow trout gill cell total protein extracts and mass spectrometric proteomic analysis was conducted to determine the composition of the protein coronas isolated by either centrifugation or magnetic retrieval. The number of washes were varied to strip away the soft coronas and isolate the hard corona. Hundreds of proteins were adsorbed to the NPs. Some proteins were common to all isolation methods and many others were particular to the isolation method. Some qualitative trends in protein character were discerned from quantitative proteomic analyses, but more importantly, a new kind of protein corona was identified, mixed corona, in which the labile or inert nature of the protein-NP interaction is dependent upon sample history.

Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis.

Safe and efficacious systemic delivery of messenger RNA (mRNA) to specific organs and cells in vivo remains the major challenge in the development of mRNA-based therapeutics. Targeting of systemically administered lipid nanoparticles (LNPs) coformulated with mRNA has largely been confined to the liver and spleen. Using a library screening approach, we identified that N-series LNPs (containing an amide bond in the tail) are capable of selectively delivering mRNA to the mouse lung, in contrast to our previous discovery that O-series LNPs (containing an ester bond in the tail) that tend to deliver mRNA to the liver. We analyzed the protein corona on the liver- and lung-targeted LNPs using liquid chromatography-mass spectrometry and identified a group of unique plasma proteins specifically absorbed onto the surface that may contribute to the targetability of these LNPs. Different pulmonary cell types can also be targeted by simply tuning the headgroup structure of N-series LNPs. Importantly, we demonstrate here the success of LNP-based RNA therapy in a preclinical model of lymphangioleiomyomatosis (LAM), a destructive lung disease caused by loss-of-function mutations in the Tsc2 gene. Our lung-targeting LNP exhibited highly efficient delivery of the mouse tuberous sclerosis complex 2 (Tsc2) mRNA for the restoration of TSC2 tumor suppressor in tumor and achieved remarkable therapeutic effect in reducing tumor burden. This research establishes mRNA LNPs as a promising therapeutic intervention for the treatment of LAM.

Interfacial Interactions within Amyloid Protein Corona Based on 2D MoS2 Nanosheets.

The interfacial interaction within the amyloid protein corona based on MoS2 nanomaterial is crucial, both for understanding the biological effects of MoS2 nanomaterial and the evolution of amyloid diseases. The specific nano-bio interface phenomenon of human islet amyloid peptide (hIAPP) and MoS2 nanosheet was investigated by using theoretical and experimental methods. The MoS2 nanosheet enables the attraction of hIAPP monomer, dimer, and oligomer on its surface through van der Waals forces. Especially, the means of interaction between two hIAPP peptides might be changed by MoS2 nanosheet. In addition, it is interesting to find that the hIAPP oligomer can stably interact with the MoS2 nanosheet in one unique "standing" binding mode with an entire exposed ß-sheet surface. All the interaction modes on the surface of MoS2 nanosheet can be the essence of amyloid protein corona that may provide the venue to facilitate the fibrillation of hIAPP proteins. Further, it was verified experimentally that MoS2 nanosheets could accelerate the fibrillation of hIAPP at a certain concentration mainly based on the newly formed nano-bio interface. In general, our results provide insight into the molecular interaction mechanism of the nano-bio interface within the amyloid protein corona, and shed light on the pathway of amyloid protein aggregation that is related to the evolution of amyloid diseases.