Effect Of Human Serum Albumin Research Articles

A systematic study of the impact of aromatic/aliphatic amines and protein corona as coatings of iron oxide magnetic nanoparticles on the interaction with DPPC Langmuir monolayers

The nature of chemical groups exposed by nanoparticles determines their interaction with biological systems, especially with cell membranes. Amino groups are one of the most used to guide nanoparticles within cells. Aromatic and aliphatic amines can establish different types of interactions with lipids, and this may condition the nanoparticles' mode of action as well as their fate. This work is focused on investigating how aromatic and aliphatic amines present at the surface of iron oxide magnetic nanoparticles influence their interaction with Langmuir monolayers as models of cell membranes. For this, we synthesized iron oxide magnetic nanoparticles coated with an arylamine (aromatic) and polyethylenimine (aliphatic). Also, the effect of human serum albumin at the particle surface was evaluated to test how protein corona governs the physicochemical properties of the nanoparticles. The interaction of these nanoparticles with monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine was systematically studied employing three different experimental approaches. The results signal a notorious influence on the type of amine in the interactions established with the phosphocholine in the model membrane. Managing this knowledge is of ongoing interest for nanomaterials design and improved bioapplications.

Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins.

The anti-inflammatory effect of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS) has been reported for 40 years. However, the short half-life of α-MSH limits its clinical applications. The previous study has shown that a fusion protein comprising protein transduction domain (PTD), human serum albumin (HSA), and α-MSH extends the half-life of α-MSH, but its anti-inflammatory effect is not satisfactory. In this study, optimization of the structures of fusion proteins was attempted by changing the linker peptide between HSA and α-MSH. The optimization resulted in the improvement of various important characteristics, especially the stability and anti-inflammatory bioactivity, which are important features in protein medicines. Compared to the original linker peptide L0, the 5-amino-acid rigid linker peptide L6 (PAPAP) is the best option for further investigation due to its higher expression (increased by 6.27%), improved purification recovery (increased by 60.8%), excellent thermal stability (Tm=83.5°C) and better inhibition in NF-κB expression (increased by 81.5%). From this study, the significance of the design of linker peptides in the study of structure-activity relationship of fusion proteins was proved.

A comparative study on the effects of human serum albumin and α-melanocyte-stimulating hormone fusion proteins on the anti-neuroinflammatory in the central nervous system of adult mice

The immunomodulatory effects of α-melanocyte stimulating hormone (α-MSH) in the central nervous system (CNS) have been investigated for forty years. The clinical applications of α-MSH are limited due to its short half-life. Our previous study has indicated that the short half-life of α-MSH can be extended by fusion with carrier human serum albumin (HSA) and this fusion protein has also retained the anti-inflammatory effect on the CNS. This improvement is still far from the clinical requirements. Thus, we expected to enhance the half-life and activity of the fusion protein by optimizing the linker peptide to get closer to clinical requirements. In a previous study, we screened out two candidates in vitro experiments with a flexible linker peptide (fusion protein with flexible linker peptide, FPFL) and a rigid linker peptide (fusion protein with rigid linker peptide, FPRL), respectively. However, it was not sure whether the anti-inflammatory effects in vitro could be reproduced in vivo. Our results show that FPRL is the best candidate with a longer half-life compared to the traditional flexible linker peptides. Meanwhile, the ability of FPRL to penetrate the blood-brain barrier (BBB) was enhanced, and the inhibition of TNF-α and IL-6 was improved. We also found that the toxicity of FPRL was decreased. All of the results suggested that trying to choose the rigid linker peptide in some fusion proteins may be a potential choice for improving the unsatisfactory characteristics.

Coupling effects of human serum albumin and sodium chloride on biological desiccation patterns

Desiccation patterns of plasma sessile drops have attracted increasing attention, not only because of the fantastic underlying physics, but also due to their potential of being health diagnostic tools. However, plasma is a multicomponent system, which contains macromolecular proteins and inorganic salts; these components have complicated interactions to define pattern morphologies. Unfortunately, mechanisms of coupling effects of main components on pattern morphologies are still not clear, thus limiting their diagnostic applications. Here we show the coupling effects of human serum albumin (HSA) and sodium chloride (NaCl) on plasma desiccation patterns. Our experiments indicate that NaCl enhances the “coffee ring” effect of HSA to promote its aggregation at the peripheral region and narrows down its aggregation area; this would influence the distribution of internal stresses, resulting in a larger number of radial cracks, with a larger width but a shorter length, than cracks in pure HSA. In the meantime, HSA experiences the gelation process that propagates from the peripheral region to central region and causes the spatiotemporal deviation in the degree of solidification, which induces a higher concentration of NaCl in the central region, thus leading to the formation of crystal patterns. Our further experiments demonstrate that these characteristic patterns are correlated to the variation in the concentration of NaCl, which can be caused by hyponatremia and hypernatremia in real biofluids. Our findings not only provide a new mechanistic insight into biological desiccation patterns, but also bridge the gap between the understanding and diagnostic applications of these desiccation patterns.

The effect of human serum albumin on ZIF-8 used in drug delivery: structural, linear and nonlinear optical properties

Zeolitic Imidazolate Frameworks (ZIF-8) are extremely useful substances that have been utilized in a variety of commercial and medical applications due to their interesting properties. Understanding the properties of ZIF-8 doped human serum albumin with different concentrations can lead to the development of new applications in areas such as sensing, drug delivery, and catalysis. Here, we investigated the extent of interaction between ZIF-8 and HSA by examining the structural, linear, and nonlinear optical properties of ZIF-8@xHSA where x is 2.5, 5, 10 wt%. Scanning electron microscope and Transmission electron microscope images revealed that both ZIF-8 and ZIF-8@10 wt% HSA had regular cubic shapes, with average particle sizes of 38 nm and 49 nm, respectively. The X-ray diffraction shows a crystalline shape for ZIF-8 and ZIF-8@10 wt% HAS. The energy gap of our composite was calculated using the Wemple-Didomenico model, and it exhibited strong concentration-dependent behavior. The Z-scanner was used to investigate the nonlinear properties, which indicated that ZIF-8@10 wt%HSA had a high nonlinear response. As the understanding of this interaction deepens, it is expected that innovative applications in biomedical and pharmaceutical fields will emerge, highlighting the vital connection between HSA and ZIF-8.

Study on the secondary structure and hydration effect of human serum albumin under acidic pH and ethanol perturbation with IR/NIR spectroscopy

Human serum albumin (HSA) is the most abundant protein in plasma and plays an essential physiological role in the human body. Ethanol precipitation is the most widely used way to obtain HSA, and pH and ethanol are crucial factors affecting the process. In this study, infrared (IR) spectroscopy and near-infrared (NIR) spectroscopy in combination with chemometrics were used to investigate the changes in the secondary structure and hydration of HSA at acidic pH (5.6–3.2) and isoelectric pH when ethanol concentration was varied from 0% to 40% as a perturbation. IR spectroscopy combined with the two-dimensional correlation spectroscopy (2DCOS) analysis for acid pH system proved that the secondary structure of HSA changed significantly when pH was around 4.5. What’s more, the IR spectroscopy and 2DCOS analysis showed different secondary structure forms under different ethanol concentrations at the isoelectric pH. For the hydration effect analysis, NIR spectroscopy combined with the McCabe–Fisher method and aquaphotomics showed that the free hydrogen-bonded water fluctuates dynamically, with ethanol at 0–20% enhancing the hydrogen-bonded water clusters, while weak hydrogen-bonded water clusters were formed when the ethanol concentration increased continuously from 20% to 30%. These measurements provide new insights into the structural changes and changes in the hydration behavior of HSA, revealing the dynamic process of protein purification, and providing a theoretical basis for the selection of HSA alcoholic precipitation process parameters, as well as for further studies of complex biological systems.

Negative interference with antibody-dependent cellular cytotoxicity mediated by rituximab from its interactions with human serum proteins.

Although interactions of small molecular drugs with serum proteins have been widely studied from pharmacokinetic and pharmacodynamic perspectives, there have been few reports on the effects of serum components on therapeutic antibody functions. This study reports the effect of abundant serum proteins on antibody-dependent cellular cytotoxicity (ADCC) mediated by rituximab and Fcγ receptor III (FcγRIII). Human serum albumin (HSA) and the Fab fragment from the pooled serum polyclonal IgG were found to compromise ADCC as non-competitive inhibitors. Our nuclear magnetic resonance data provided direct evidence for the interactions of HSA with both the Fab and Fc regions of rituximab and also with the extracellular region of FcγRIII (sFcγRIII). The degree of involvement in the interaction decreased in the order of rituximab-Fab > rituximab-Fc > sFcγRIII, suggesting preferential binding of HSA to net positively charged proteins. Although much less pronounced than the effect of HSA, polyclonal IgG-Fab specifically interacted with rituximab-Fc. The NMR data also showed that the serum protein interactions cover the Fc surface extensively, suggesting that they can act as pan-inhibitors against various Fc receptor-mediated functions and pharmacokinetics. Our findings highlight the importance of considering serum-protein interactions in the design and application of antibody-based drugs with increased efficacy and safety.

Influence of bovine and human serum albumin on the binding kinetics of biomolecular interactions.

Bovine serum albumin (BSA) containing buffers are the standard blocking buffer in biosensing, yet human serum is the intended application for most clinical sensors. However, the effect of human serum albumin (HSA) on binding assays remains underexplored. A simple and well-studied assay (human IgG/goat anti-human IgG) was investigated with a surface plasmon resonance (SPR) sensor to address this fundamental question in sensing. Calibrations were performed with buffers containing various concentrations of bovine or human serum albumin, as well as full and diluted bovine or IgG-depleted human serum. It was found that HSA or human serum, but not BSA or bovine serum, significantly affected the SPR shift and binding constants of the assay. Interestingly, large differences were also observed depending on whether the animal or human antibody was immobilized on the SPR chip for detection, highlighting that matrix protein/analyte/receptor interactions play a significant role in the response. We find that the interaction of soluble HSA with human IgG interferes with the recognition region, affecting the binding constant, and thus results obtained in BSA are not necessarily applicable to clinical samples or in vivo conditions. We also clearly demonstrate why a minimum dilution of 1 : 10 is often required in SPR assays to remove most background effects. Taken together, these results show that: (1) BSA does not affect the binding constant between antibodies and thus serves its purpose well when only surface blocking is intended, (2) HSA is an adequate surrogate for human serum in assay optimization, and (3) blocking buffers should be prepared with HSA in the optimization steps of assays to be translated to human blood or serum.

Human serum albumin promotes self-renewal and expansion of umbilical cord blood CD34+ hematopoietic stem/progenitor cells.

We investigated the effect of human serum albumin (HSA) on human umbilical cord blood (UCB) CD34+ hematopoietic stem/progenitor cells (HSPCs) cultured in vitro and transplanted in vivo. Human umbilical cord blood mononuclear cells were obtained by density gradient centrifugation. CD34+ cells were then sorted by CD34 conjugated magnetic microbeads. The sorted cells were cultured with or without HSA for 8 days in vitro. After 8 days, all cells were harvested for flow phenotyping and colony formation cell (CFC) experiments. The cells were injected into immunodeficient mice (NOD/Shi-scid/IL2Rγnull, NOG) via intravenous injections. From 4 weeks post-transplantation, flow cytometry was used to calculate human cell chimerism in the peripheral blood (PB) every 2 weeks. Flow phenotyping of human cell chimerism in bone marrow and spleen was calculated 16 weeks post-transplantation. Compared to the control group, CD34+ cells cultured with HSA increased significantly in vitro. The long-term engraftment of HSPCs and the hematopoietic multilineage reconstruction capacity were preserved by HSA. Normal engraftment of human cells could be maintained via HSA treatment could maintain normal engraftment of human cells in recipient PB. Here, we found that HSA was beneficial to maintaining CD34+ cell expansion and short-term colony formation in vitro and optimizing multilineage reconstitution in immunodeficient mice in vivo.

Effects of Human Serum Albumin on the Fluorescence Intensity and Tumor Imaging Properties of IR-780 Dye.

IR-780 is a lipophilic dye with excellent optical and tumor imaging properties for early tumor diagnostics. Although the mechanism of tumor targeting has not been fully identified, the view that serum albumin plays an important role in tumor accumulation has been recognized. Here, the mechanism of the interaction between IR-780 and HSA was studied to explore the effect of albumin on its tumor targeting properties. Data demonstrate that IR-780 can be tightly adsorbed by HSA at a ratio of 1:1 to form a noncovalent complex, which exhibits significant improvement in the near-infrared fluorescence imaging and tumor diagnosis capacity. During this process, the endogenous fluorescence and esterase activity of HSA are both partially inhibited by IR-780, and the α-helical content of HSA slightly increases. Molecular docking simulation displays that the binding site of IR-780 on HSA is between subdomains IIA and IIB. These results indicate that HSA is an important factor to mediate the optical performance of IR-780, giving it higher tumor diagnosis capability.

Improving light-sensing behavior of Cu/n-Si photodiode with Human Serum Albumin: Microelectronic and dielectric characterization

This research was mainly focused on the investigation of the effect of Human Serum Albumin (HSA) on the electrical features of Cu/n-Si device. To do this, HSA layer was grown as an interfacial layer between Cu and n-Si to create Cu/HSA/n-Si device. To investigate the performance of the obtained device architecture in optoelectronic applications, the electrical and photo-response properties of the device were evaluated by current-voltage measurements at different light power intensities. The results show that as well as the device showed a good rectification characteristic in the dark, it also showed that it exhibits a good photodiode property at different light intensities. Besides, main diode parameters such as ideality factor, effective barrier height, and series resistance were evaluated by thermionic emission theory and Cheung approximation. Obtained results from both calculation methods revealed that diode parameters highly depend on the light power intensity. This variation in the diode parameter is explained in detail taking electron-hole formation in the HSA and n-Si into consideration. Besides, the capacitive properties of the device were investigated with capacitance-voltage measurements in the frequency range of 200 and 1000 kHz and it was observed that the device exhibits capacitive properties in this range. Furthermore, main dielectric parameters such as dielectric constant, dielectric loss, and loss tangent were also evaluated by using impedance spectroscopy in the different frequency range and results showed that all-dielectric parameters highly depend on frequency. All obtained results have been discussed in detail.

Structural Basis of Alpha Synuclein Assembly Toxicity Inhibition by Human Serum Albumin

The generation of oligomeric intermediates arising during the aggregation of alpha synuclein (αS) is a central feature of Lewy body diseases such as Parkinson's disease (PD). Recent findings suggest that trace amounts of αS are released into the extracellular environment by unconventional exocytosis from neurons, and that these extracellular species contribute to the pathology observed in PD. Extracellular chaperones, such as Human Serum Albumin (HSA), have been shown to inhibit the self-association of αS. However, the mechanism underlying αS aggregation inhibition by the endogenous fatty acid (FA)-transporter HSA remains poorly understood. By combining solution NMR with biolayer interferometry, dynamic light scattering, electron microscopy, wide-angle X-ray diffraction, size exclusion chromatography coupled with multiple angle light scattering, fluorescence spectroscopy and cell viability assays, we provide an unprecedented mechanism of αS assembly (αSn) toxicity inhibition by HSA. Here we show that HSA binds αSn­ with sub µM affinity through hydrophobic interactions that are independent of FA binding to the two high-affinity sites in HSA. HSA-binding of αSn shifts the populations of low molecular weight (MW) oligomers and high MW fibrils into “worm-like” intermediates with reduced toxicity and, concurrently, perturbs the conversion of NMR-visible monomers into NMR-invisible αSn. Notably, we show that HSA inhibits the interaction of αSn with membranes and that the effects of HSA and membrane addition to αSn are non-additive, arising possibly from the direct interactions of HSA with membranes. These results reveal that extracellular chaperoneshelp maintain protein homeostasisnot only by assisting the folding and assembly of proteins,but unexpectedly, also suppressing aberrant interactions with membranes, which promote the formation of toxic intermediates and enhance neuronal dysfunction.

Pengaruh Pemberian Serum Albumin Manusia terhadap Kadar Albumin dalam Darah pada Anjing dengan status Hipoalbuminemia

Albumin consists of 50% of the total plasma protein and it is very important protein in the animal's body. Hypoalbuminemia can occurs due to various conditions, such as loss of protein nephropathy, loss of enteropathic proteins, chronic and acute diarrhea or heavy bleeding as well as malnutrition and malabsorption conditions. This study aims to determine the effect of human serum albumin 20% infusion to increase albumin blood level in hypoalbuminemia dogs. Animals used in this study were 5 dogs whose results showed the levels of albumin below normal limits or hypoalbuminemia. Dogs with hypoalbuminemia will be infused with human serum albumin (HSA) 20% through intravenous for ± 4 hours. Then, these dogs blood will be drawn days after infusion to screen for albumin levels. The results obtained in the form of examination data of albumin blood levels in the blood before and after infusion will be analyzed with paired T-test. The results showed an increase of albumin level significantly from an average of 1.98 ± 0.356 to 2.28 ± 0.257(P <0.05). This study shows the presence of human albumin serum through intravenous infusion was able to increase albumin levels in dogs with hypoalbuminemia.

Dissecting the Interactions between Human Serum Albumin and α-Synuclein: New Insights on the Factors Influencing α-Synuclein Aggregation in Biological Fluids.

α-Synuclein (α-syn) is found to be naturally present in biofluids such as cerebrospinal fluid (CSF) and serum. Human serum albumin (HSA) is the most abundant protein found in these biofluids, which, beyond transporting hormones and drugs, also exerts a chaperone-like activity binding other proteins in blood and inhibiting their aggregation. Contrasting results are reported in the literature about the effects of albumin on α-syn aggregation. We characterized the binding region of HSA on α-syn by high-field solution NMR spectroscopy and the effect of HSA on α-syn aggregation by thioflavin-T (ThT) fluorescence under both low-ionic-strength and physiological conditions at the albumin concentration in serum and CSF. We found that HSA, at the concentration found in human serum, slows the aggregation of α-syn significantly. α-Syn interacts with HSA in an ionic strength- and pH-dependent manner. The binding is driven by hydrophobic interactions at the N-terminus under physiological experimental conditions and by electrostatic interactions at the C-terminus at low ionic strength. This work provides novel information about the proteostasis of α-syn in biofluids and supports the hypothesis of a chaperone-like behavior of HSA.

Interaction of 2'R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated coffee results in the formation of 2′R-ochratoxin A (2′R-OTA), which appears in the blood of coffee drinkers. Human serum albumin (HSA) binds 2′R-OTA (and OTA) with high affinity; therefore, albumin may influence the tissue uptake and elimination of ochratoxins. We aimed to investigate the binding site of 2′R-OTA (verses OTA) in HSA and the displacing effects of site markers to explore which molecules can interfere with its albumin-binding. Affinity of 2′R-OTA toward albumins from various species (human, bovine, porcine and rat) was tested to evaluate the interspecies differences regarding 2′R-OTA-albumin interaction. Thermodynamic studies were performed to give a deeper insight into the molecular background of the complex formation. Besides fluorescence spectroscopic and modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of 2′R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the influence of albumin-binding on the cellular uptake of ochratoxins. Site markers displaced more effectively 2′R-OTA than OTA from HSA. Fluorescence and binding constants of 2′R-OTA-albumin and OTA-albumin complexes showed different tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2′R-OTA, even at sub-toxic concentrations, increased the toxic action of OTA.

Interactions of Silver Nanoparticles Formed in Situ on AFM Tips with Supported Lipid Bilayers.

A facile approach for functionalizing atomic force microscopy (AFM) tips with nanoparticles (NPs) will provide exciting opportunities in the field of tip-enhanced vibrational spectroscopy and in probing the interactions between NPs and biological systems. In this study, through successive exposure to polydopamine and AgNO3 solutions, the apex of AFM tips was functionalized with silver nanoparticles (AgNPs). The AgNP-modified AFM tips were used to measure the interaction forces between AgNPs and supported lipid bilayers (SLBs) formed on mica, as well as to probe the penetration of SLBs by AgNPs, with an emphasis on the effect of human serum albumin (HSA) proteins. AgNPs experienced predominantly repulsive forces when approaching SLBs. The presence of HSA resulted in an enhancement in the repulsive interactions between AgNPs and SLBs, likely through steric repulsion. Finally, the forces required for AgNPs to penetrate SLBs were higher in the presence of HSA probably due to the increase in the effective size of the nanoscale protuberances on the AFM tip stemming from the formation of protein coronas around the AgNPs.

Repeated Oral Administration of Human Serum Albumin Protects from the Cerebral Ischemia in Rat Brain Following MCAO.

Albumin is known to have neuroprotective effects. The protein has a long half-life circulation, and its effects can therefore persist for a long time to aid in the recovery of brain ischemia. In the present study, we investigated the neuroprotective effects of human serum albumin (HSA) on brain hemodynamics. Albumin is administrated using repeated oral gavage to the rodents. Sprague-Dawley rats underwent middle cerebral artery occlusion procedures and served as a stroke model. Afterwards, 25% human serum albumin (1.25 g/kg) or saline (5 ml/kg) was orally administrated for 2 weeks in alternating days. After 2 weeks, the rodents were assessed for levels of brain ischemia. Our testing battery consists of behavioral tests and in vivo optical imaging sessions. Modified neurological severity scores (mNSS) were obtained to assess the levels of ischemia and the effects of HSA oral administration. We found that the experimental group demonstrated larger hemodynamic responses following sensory stimulation than controls that were administered with saline. HSA administration resulted in more significant changes in cerebral blood volume following direct cortical electric stimulation. In addition, the mNSS of the treatment group was lower than the control group. In particular, brain tissue staining revealed that the infarct size was also much smaller with HSA administration. This study provides support for the efficacy of HSA, and that long-term oral administration of HSA may induce neuroprotective effects against brain ischemia.

THERMODYNAMIC EFFECTS OF SERUM ALBUMIN INTERACTION WITH SHUNGITE NANOCARBON

The bioactivity features of shungite nanocarbon (ShC) as a new ultrafine carbon form are of particular interest from the point of view of both biomedical applications of the nanomaterial and environmental issues. Thermodynamic effects of human serum albumin (SA) interaction with ShC in water nanodispersion have been studied regarding the molecular structure and protein fraction content using differential scanning calorimetry. Deconvolution of the albumin denaturation curve on the basis of Gaussian functions was used to analyze the characteristics (temperature, enthalpy) of individual endothermic transitions of the protein. The increase of the temperature difference of individual transitions was found to be the major SA-ShC interaction effect. No overall thermal destabilization of the protein was observed, although some partial destabilization did occur. This result cannot ensue from changes in intramolecular interdomain interactions in protein molecules at intermolecular interactions with ShC since only a small part of the total protein in nanodispersion has access to nanoparticle surface. The effects observed are shown to be related to the ShC influence on the ratio of the protein fractions with different fatty acids (FA) content by affecting some part of FA at their protein binding sites and their transition to nanoparticles. Protein and nanocarbon probably compete for FA in the process, and their concentration ratio in the dispersion is of decisive importance. The significance of this sort of competition consists in the possibility to influence the transport function of serum albumin with respect to FA.

Aberrant Co-localization of Synaptic Proteins Promoted by Alzheimer's Disease Amyloid-β Peptides: Protective Effect ofHuman Serum Albumin.

Amyloid-β (Aβ), Aβ40, Aβ42, and, recently, Aβ25-35 have been directly implicated in the pathogenesis of Alzheimer’s disease. We have studied the effects of Aβ on neuronal death, reactive oxygen species (ROS) production, and synaptic assembling in neurons in primary culture. Aβ25-35, Aβ40, and Aβ42 significantly decreased neuronal viability, although Aβ25-35 showed a higher effect. Aβ25-35 showed a more penetrating ability to reach mitochondria while Aβ40 did not enter the neuronal cytosol and Aβ42 was scarcely internalized. We did not observe a direct correlation between ROS production and cell death because both Aβ40 and Aβ42 decreased neuronal viability but Aβ40 did not change ROS production. Rather, ROS production seems to correlate with the penetrating ability of each Aβ. No significant differences were found between Aβ40 and Aβ42 regarding the extent of the deleterious effects of both peptides on neuronal viability or synaptophysin expression. However, Aβ40 elicited a clear delocalization of PSD-95 and synaptotagmin from prospective synapsis to the neuronal soma, suggesting the occurrence of a crucial effect of Aβ40 on synaptic disassembling. The formation of Aβ40- or Aβ42-serum albumin complexes avoided the effects of these peptides on neuronal viability, synaptophysin expression, and PSD-95/synaptotagmin disarrangement suggesting that sequestration of Aβ by albumin prevents deleterious effects of these peptides. We can conclude that Aβ borne by albumin can be safely transported through body fluids, a fact that may be compulsory for Aβ disposal by peripheral tissues.

Synergistic Effect of Human Serum Albumin and Fullerene on Gd-DO3A for Tumor-Targeting Imaging.

A macromolecular magnetic resonance imaging (MRI) contrast agent was successfully synthesized by conjugating the gadolinium/1,4,7,10-tetraazacyclododecane-1,4,7-tetracetic acid complex (Gd-DO3A) with 6,6-phenyl-C61 butyric acid (PC61BA) and upon further modification with human serum albumin (HSA). The final product, PC61BA-(Gd-DO3A)/HSA, has a high stability and exhibits a much higher relaxivity (r1 = 89.1 mM(-1) s(-1) at 0.5 T, 300 K) than Gd-DO3A (r1 = 4.7 mM(-1) s(-1)) does under the same condition, producing the synergistic positive effect of HSA and C60 on the relaxivity of Gd-DO3A. The in vivo MR images of PC61BA-(Gd-DO3A)/HSA-treated tumor-bearing mice show strong signal enhancement for the tumor area due to the enhanced permeability and retention effect. The maximum accumulation of PC61BA-(Gd-DO3A)/HSA at the tumor site was achieved at 4 h postinjection, which may guide surgery. The results from the hematology and histological observations indicate that PC61BA-(Gd-DO3A)/HSA has no obvious toxicity in vivo. These unique properties of PC61BA-(Gd-DO3A)/HSA enable them to be highly efficient for tumor-targeting MRI in vivo, possibly providing a good solution for tumor diagnosis.