Selection of collagen IV fragments forming the outer sphere of the native protein: Assessment of biological activity for regenerative medicine.

The aim of this research was to select the fragments that make up the outer layer of the collagen IV (COL4A6) protein and to assess their potential usefulness for regenerative medicine. It was expected that because protein-protein interactions take place via contact between external domains, the set of peptides forming the outer sphere of collagen IV will determine its interaction with other proteins. Cellulose-immobilized protein fragment libraries treated with polyclonal anti-collagen IV antibodies were used to select the peptides forming the outer sphere of collagen IV. In the first test, 33 peptides that strongly interacted with the polyclonal anti-collagen IV antibodies were selected from a library of non-overlapping fragments of collagen IV. The selected fragments of collagen IV (cleaved from the cellulose matrix) were tested for their cytotoxicity, their effects on cell viability and proliferation, and their impact on the formation of reactive oxygen species (ROS). The studies used RAW 264.7 mouse macrophage cells and Hs 680.Tr human fibroblasts. PrestoBlue, ToxiLight™, and ToxiLight 100% Lysis Control assays were conducted. The viability of fibroblasts cultured with the addition of increasing concentrations of the peptide mix did not show statistically significant differences from the control. Fragments 161-170, 221-230, 721-730, 1331-1340, 1521-1530, and 1661-1670 of COL4A6 were examined for cytotoxicity against BJ normal human foreskin fibroblasts. None of the collagen fragments were found to be cytotoxic. Further research is underway on the potential uses of collagen IV fragments in regenerative medicine.

Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity.

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g., in the treatment of neurodegenerative diseases, which have a problem of the blood-brain barrier (BBB) restricting drug delivery. Numerous studies have been conducted to find appropriate drug carriers that are safe, biocompatible and efficient. In this work, we evaluate pegylated gold nanoparticles AuNP14a and AuNP14b after their conjugation with therapeutic siRNA directed against APOE4. This genetic risk factor remains the strongest predictor for late-onset Alzheimer's disease. The study aimed to assess the biophysical properties of AuNPs/siAPOE complexes and to check their biological safety on healthy cells using human brain endothelial cells (HBEC-5i). Techniques such as fluorescence polarization, circular dichroism, dynamic light scattering, ζ-potential measurements and gel retardation assay showed that AuNPs form stable complexes with siRNA. Subsequently, cytotoxicity assays proved the biological safety of formed conjugates. Obtained results enabled us to find effective concentrations of AuNPs when complexes are formed and non-toxic for healthy cells. One of the studied nanoparticles, AuNP14b complexed with siRNA, displayed lower cytotoxicity (MTT assay, cells viability -74.8 ± 3.1%) than free nanoparticles (44.7 ± 3.6%). This may be promising for further investigations in nucleic acid delivery and could have practical use in treating neurodegenerative diseases.

The Anti-Aggregative Potential of Resolvin E1 on Human Platelets.

Resolvin E1 is a metabolite of eicosapentaenoic acid (EPA) which is one of the omega-3 polyunsaturated fatty acids (omega-3 PUFAs). The antiplatelet properties of omega-3 PUFAs are well known, but the effect of resolvin E1 on platelets via the collagen receptors is extremely poorly reported. We investigated the effect of resolvin E1 on collagen-induced platelet aggregation, activation, and reactivity, and also platelet membrane fluidity. The ultimate and statistically significant results showed that resolvin E1 may inhibit platelet reactivity due to the reduction of collagen-induced platelet aggregation in platelet-rich plasma and isolated platelets, but not in whole blood. Also, resolvin E1 significantly reduced P-selectin exposure on collagen-stimulated platelets. Moreover, we demonstrated that resolvin E1 can maintain platelet membrane structure (without increasing membrane fluidity). The association between platelet reactivity and membrane fluidity, including resolvin E1 and collagen receptors requires further research. However, the goal of this study was to shed light on the molecular mechanisms behind the anti-aggregative effects of resolvin E1 on platelets, which are still not fully clarified. We also indicate an innovative research direction focused on further analysis and then use of omega-3 PUFAs metabolites as antiplatelet compounds for future applications in the treatment and prevention of cardiovascular diseases.

Glassy-like Metal Oxide Particles Embedded on Micrometer Thicker Alginate Films as Promising Wound Healing Nanomaterials.

Micrometer-thicker, biologically responsive nanocomposite films were prepared starting from alginate-metal alkoxide colloidal solution followed by sol-gel chemistry and solvent removal through evaporation-induced assembly. The disclosed approach is straightforward and highly versatile, allowing the entrapment and growth of a set of glassy-like metal oxide within the network of alginate and their shaping as crake-free transparent and flexible films. Immersing these films in aqueous medium triggers alginate solubilization, and affords water-soluble metal oxides wrapped in a biocompatible carbohydrate framework. Biological activity of the nano-composites films was also studied including their hemolytic activity, methemoglobin, prothrombin, and thrombine time. The effect of the films on fibroblasts and keratinocytes of human skin was also investigated with a special emphasis on the role played by the incorporated metal oxide. This comparative study sheds light on the crucial biological response of the ceramic phase embedded inside of the films, with titanium dioxide being the most promising for wound healing purposes.

Synthesis and Hemostatic Activity of New Amide Derivatives.

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine-natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO- (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1-8 were similar. The obtained results in the presence of amides 1-4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson's Disease Patient-Specific Dopamine Neurons.

Accumulation of misfolded α-synuclein (α-syn) is a hallmark of Parkinson's disease (PD) thought to play important roles in the pathophysiology of the disease. Dendritic systems, able to modulate the folding of proteins, have emerged as promising new therapeutic strategies for PD treatment. Dendrimers have been shown to be effective at inhibiting α-syn aggregation in cell-free systems and in cell lines. Here, we set out to investigate the effects of dendrimers on endogenous α-syn accumulation in disease-relevant cell types from PD patients. For this purpose, we chose cationic carbosilane dendrimers of bow-tie topology based on their performance at inhibiting α-syn aggregation in vitro. Dopamine neurons were differentiated from induced pluripotent stem cell (iPSC) lines generated from PD patients carrying the LRRK2G2019S mutation, which reportedly display abnormal accumulation of α-syn, and from healthy individuals as controls. Treatment of PD dopamine neurons with non-cytotoxic concentrations of dendrimers was effective at preventing abnormal accumulation and aggregation of α-syn. Our results in a genuinely human experimental model of PD highlight the therapeutic potential of dendritic systems and open the way to developing safe and efficient therapies for delaying or even halting PD progression.

Thermodynamic Studies of Interactions between Sertraline Hydrochloride and Randomly Methylated ß-Cyclodextrin Molecules Supported by Circular Dichroism Spectroscopy and Molecular Docking Results.

The interaction between sertraline hydrochloride (SRT) and randomly methylated ß-cyclodextrin (RMßCD) molecules have been investigated at 298.15 K under atmospheric pressure. The method used-Isothermal Titration Calorimetry (ITC) enabled to determine values of the thermodynamic functions like the enthalpy (ΔH), the entropy (ΔS) and the Gibbs free energy (ΔG) of binding for the examined system. Moreover, the stoichiometry coefficient of binding (n) and binding/association constant (K) value have been calculated from the experimental results. The obtained outcome was compared with the data from the literature for other non-ionic ßCD derivatives interacting with SRT and the enthalpy-entropy compensation were observed and interpreted. Furthermore, the connection of RMßCD with SRT was characterized by circular dichroism spectroscopy (CD) and complexes of ßCD derivatives with SRT were characterized through the computational studies with the use of molecular docking (MD).

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films.

Marine polysaccharides are believed to be promising wound-dressing nanomaterials because of their biocompatibility, antibacterial and hemostatic activity, and ability to easily shape into transparent films, hydrogels, and porous foams that can provide a moist micro-environment and adsorb exudates. Current efforts are firmly focused on the preparation of novel polysaccharide-derived nanomaterials functionalized with chemical objects to meet the mechanical and biological requirements of ideal wound healing systems. In this contribution, we investigated the characteristics of six different cellulose-filled chitosan transparent films as potential factors that could help to accelerate wound healing. Both microcrystalline and nano-sized cellulose, as well as native and phosphorylated cellulose, were used as fillers to simultaneously elucidate the roles of size and functionalization. The assessment of their influences on hemostatic properties indicated that the tested nanocomposites shorten clotting times by affecting both the extrinsic and intrinsic pathways of the blood coagulation system. We also showed that all biocomposites have antioxidant capacity. Moreover, the cytotoxicity and genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. The nature of the cellulose used as a filler was found to influence their cytotoxicity at a relatively low level. Potential mechanisms of cytotoxicity were also investigated; only one (phosphorylated microcellulose-filled chitosan films) of the compounds tested produced reactive oxygen species (ROS) to a small extent, and some films reduced the level of ROS, probably due to their antioxidant properties. The transmembrane mitochondrial potential was very slightly lowered. These biocompatible films showed no genotoxicity, and very importantly for wound healing, most of them significantly accelerated migration of both fibroblasts and keratinocytes.

The Interaction of Heptakis (2,6-di-O-Methyl)-ß-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity.

One tetracyclic antidepressant, mianserin hydrochloride (MIA), has quite significant side effects on a patients' health. Cyclodextrins, which are most commonly used to reduce the undesirable features of contained drugs within their hydrophobic interior, also have the potential to alter the toxic behavior of the drug. The present paper contains investigations and the characteristics of interaction mechanisms for MIA and the heptakis (2,6-di-O-methyl)-ß-cyclodextrin (DM-ß-CD) system, and evaluated the effects of the complexation on MIA cytotoxicity. In order to assess whether there was an interaction between MIA and DM-ß-CD molecules, isothermal titration calorimetry (ITC) have been chosen. Electrospray ionization mass spectrometry (ESI-MS) helped to establish the complex stoichiometry, and circular dichroism spectroscopy was used to describe the process of complex formation. In order to make a wider interpretative perspective, the molecular docking results have been performed. The viability of Chinese hamster cells were investigated in the presence of DM-ß-CD and its complexes with MIA in order to estimate the cytotoxicity of the drug and the conjugate with the chosen cyclodextrin. The viability of B14 cells treated with MIA+DM-ß-CD is lower (the toxicity is higher) than with MIA alone, and no protective effects have been observed for complexes of MIA with DM-ß-CD in any ratio.

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells.

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.

Antimicrobial Effect of Chitosan Films on Food Spoilage Bacteria.

Synthetic materials commonly used in the packaging industry generate a considerable amount of waste each year. Chitosan is a promising feedstock for the production of functional biomaterials. From a biological point of view, chitosan is very attractive for food packaging. The purposes of this study were to evaluate the antibacterial activity of a set of chitosan-metal oxide films and different chitosan-modified graphene (oxide) films against two foodborne pathogens: Campylobacter jejuni ATCC 33560 and Listeria monocytogenes 19115. Moreover, we wanted to check whether the incorporation of antimicrobial constituents such as TiO2, ZnO, Fe2O3, Ag, and graphene oxide (GO) into the polymer matrices can improve the antibacterial properties of these nanocomposite films. Finally, this research helps elucidate the interactions of these materials with eukaryotic cells. All chitosan-metal oxide films and chitosan-modified graphene (oxide) films displayed improved antibacterial (C. jejuni ATCC 33560 and L. monocytogenes 19115) properties compared to native chitosan films. The CS-ZnO films had excellent antibacterial activity towards L. monocytogenes (90% growth inhibition). Moreover, graphene-based chitosan films caused high inhibition of both tested strains. Chitosan films with graphene (GO, GOP, GOP-HMDS, rGO, GO-HMDS, rGOP), titanium dioxide (CS-TiO2 20:1a, CS-TiO2 20:1b, CS-TiO2 2:1, CS-TiO2 1:1a, CS-TiO2 1:1b) and zinc oxide (CS-ZnO 20:1a, CS-ZnO 20:1b) may be considered as a safe, non-cytotoxic packaging materials in the future.

Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34.

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.

Spheroids as a Type of Three-Dimensional Cell Cultures-Examples of Methods of Preparation and the Most Important Application.

Cell cultures are very important for testing materials and drugs, and in the examination of cell biology and special cell mechanisms. The most popular models of cell culture are two-dimensional (2D) as monolayers, but this does not mimic the natural cell environment. Cells are mostly deprived of cell-cell and cell-extracellular matrix interactions. A much better in vitro model is three-dimensional (3D) culture. Because many cell lines have the ability to self-assemble, one 3D culturing method is to produce spheroids. There are several systems for culturing cells in spheroids, e.g., hanging drop, scaffolds and hydrogels, and these cultures have their applications in drug and nanoparticles testing, and disease modeling. In this paper we would like to present methods of preparation of spheroids in general and emphasize the most important applications.

Evaluation of the Effect of Selected Brominated Flame Retardants on Human Serum Albumin and Human Erythrocyte Membrane Proteins.

Brominated flame retardants (BFRs) have been using to reduce the flammability of plastics contained in many products, such as household articles, furniture, mattresses, textiles or insulation. Considering the fact that these compounds may be released into the environment leading to the exposure of living organisms, it is necessary to study their possible effects and mechanisms of action. Proteins play a crucial role in all biological processes. For this reason, a simple model of human serum albumin (HSA) was chosen to study the mechanism of BFRs' effect on proteins. The study determined interactions between selected BFRs, i.e., tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP), and HSA by measurement of fluorescence of intrinsic tryptophan and absorbance of circular dichroism (CD). In addition, in order to understand the possible effect of these compounds in their native environment, the effect of BFRs on membrane proteins of human erythrocytes (red blood cells, RBCs) was also assessed. Among bromophenols, PBP had the strongest oxidative effect on RBC membrane, and 2,4-DBP demonstrated the weakest fluorescence-quenching effect of both membrane tryptophan and HSA. By contrast to PBP, 2,4-DBP and 2,4,6-TBP caused spatial changes of HSA. We have observed that among all analyzed BFRs, TBBPA caused the strongest oxidation of RBC membrane proteins and the model HSA protein, causing reduction of fluorescence of tryptophan contained in them. TBBPA also changed albumin conformation properties, leading to impairment of the α-helix structure. However, TBBPS had the weakest oxidative effect on proteins among studied BFRs and did not affect the secondary structure of HSA.

Cytotoxic activity of genistein-8-C-glucoside form Lupinus luteus L. and genistein against human SK-OV-3 ovarian carcinoma cell line.

Genistein belongs to isoflavones, which are a subclass of flavonoids, a large group of polyphenolic compounds widely distributed in plants. Numerous in vitro studies suggest that isoflavones, particularly genistein, have both chemopreventive and chemotherapeutic potential in multiple tumor types. However, the molecular and cellular mechanisms of genistein effects on human ovarian cancer cells are still little known. In the present study, we investigated anticancer activity of genistein and its natural glucoside, genistein-8-C-glucoside isolated from flowers of Lupinus luteus L. We examined the effects of the two isoflavones alone or in combination on cultured human SK-OV-3 ovarian carcinoma cells. The cells were exposed to genistein and genistein-8-C-glucoside at various concentrations (1-90 µM) for 24 and 48 h. The cytotoxic and apoptotic properties of compounds were studied by the colorimetric 3-[4,5-2-yl]-2-5-diphenyltetrazolium bromide assay and the acridine orange/ethidium bromide staining technique. The morphological features of SK-OV-3 cells were examined by Nomarski differential interference contrast combined with a confocal laser scanning microscope. The level of ROS was evaluated with fluorescence probes: dichlorofluorescein-diacetate by flow cytometry. Changes in mitochondrial membrane potential were determined using 5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzimidazolcarbocyanine iodide. Genistein-treatment and genistein-8-C-glucoside-treatment resulted in the inhibition of cell proliferation, induction of apoptotic cell death and loss of mitochondrial membrane potential. The present data provide the first evidence in vitro that genistein-8-C-glucoside and combination genistein-genistein-8-C-glucoside could be a potential chemotherapeutic candidate for ovarian cancer therapy.

Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid monolayers.

AIMS: We have investigated the effect of surface charge of model lipid membranes on their interactions with dendriplexes formed by HIV-derived peptides and 2 types of positively charged carbosilane dendrimers (CBD). METHODS: Interaction of dendriplexes with lipid membranes was measured by fluorescence anisotropy, dynamic light scattering and Langmuir-Blodgett techniques. The morphology of the complexes was examined by transmission electron microscopy. RESULTS: All dendriplexes independent of the type of peptide interacted with model lipid membranes. Negatively charged vesicles composed of a mixture of DMPC/DPPG interacted more strongly, and it was accompanied by an increase in anisotropy of the fluorescent probe localized in polar domain of lipid bilayers. There was also an increase in surface pressure of the lipid monolayers. Mixing negatively charged liposomes with dendriplexes increased liposome size and made their surface charges more positive. CONCLUSIONS: HIV-peptide/dendrimer complexes interact with model lipid membranes depending on their surface charge. Carbosilane dendrimers can be useful as non-viral carriers for delivering HIV-peptides into cells.

Oleochemical-tethered SBA-15-type silicates with tunable nanoscopic order, carboxylic surface, and hydrophobic framework: cellular toxicity, hemolysis, and antibacterial activity.

Novel silicates were prepared by using silylated natural fatty acids (derived from triglyceride renewable oils) as co-condensing reagents in presence of tetraethyl orthosilicate (TEOS) and the triblock copolymer, pluronic P123, as a structure directing agent. A series of carboxylic acid functionalized SBA-15-type mesoporous silicates were obtained with tunable nanoscopic order and reactive functional groups that allow the conjugation of amino probes by peptide coupling. Photophysical studies of the covalently linked aminopyrene substantiated that the internal framework of these materials have pronounced hydrophobicity. Moreover, phase separation that can emanate from the bulkiness of the starting fatty silanes has been ruled out owing to the absence of excimers after aminopyrene grafting. The hemotoxicity, cytotoxicity, and antimicrobial activity of these novel silicates were then evaluated. Without discrimination, the functionalized silicates show a significant decrease of red blood cell hemolysis as compared to bare SBA-15-silica material. Within the modified silicate series, germanium-free mesoporous silicates induce only a slight decrease in cell viability and, more interestingly, they exhibit negligible hemolytic effect. Moreover, increasing their concentration in the medium reduces the concentration of released hemoglobin as a result of Hb adsorption. Promising antimicrobial properties were also observed for these silicates with a slight dependency on whether phenylgermanium fragments were present within the silicate framework.

[Applications of electromagnetic radiation in medicine]. / Zastosowanie promieniowania elektromagnetycznego w medycynie.

Recent decades have been devoted to the intense search for the response to questions related to the impact of radiation on the human body. Due to the growing fashion for a healthy lifestyle, increasing numbers of works about the alleged dangers of electromagnetic waves and diseases that they cause appeared. However, the discoveries of 20th century, and knowledge of the properties of electromagnetic radiation have allowed to broaden the horizons of the use of artificial sources of radiation in many fields of science and especially in medicine. The aim of this paper is to show that although excessive radiation or high doses are dangerous to the human body, its careful and controlled use, does not pose a threat, and it is often necessary in therapy. The possibility of using ionizing radiation in radiotherapy, isotope diagnostics or medical imaging, and non-ionizing radiation in the treatment for dermatological disorders and cancers will be presented. The unique properties of synchrotron radiation result in using it on a large scale in the diagnosis of pathological states by imaging methods.

Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers.

Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood-brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system. In this study, we investigated the biophysical properties of dendrimers and their complexes with siRNA directed against the apolipoprotein E (APOE) gene to identify an appropriate nanocarrier capable of safely delivering the cargo across the BBB. Our study yielded valuable insights into the complexation process, stability over time, the mechanisms of interaction, the influence of dendrimers on the oligonucleotide's spatial structure, and the potential cytotoxic effects on human cerebral microvascular endothelium cells. Based on our findings, we identified that the dendrimer G3Si PEG6000 was an optimal candidate for further research, potentially serving as a nanocarrier capable of safely delivering therapeutic agents across the BBB for the treatment of neurodegenerative disorders.

Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

Inhibition of α-synuclein (ASN) fibril formation is a potential therapeutic strategy in Parkinson's disease and other synucleinopathies. The aim of this study was to examine the role of viologen-phosphorus dendrimers in the α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with phosphonate and pegylated surface-reactive viologen-phosphorus dendrimers were examined by measuring the zeta potential, which allowed determining the number of dendrimer molecules that bind to the ASN molecule. The fibrillation kinetics and the structural changes were examined using ThT fluorescence and CD spectroscopy. Depending on the concentration of the used dendrimer and the nature of the reactive groups located on the surface, ASN fibrillation kinetics can be significantly reduced, and even, in the specific case of phosphonate dendrimers, the fibrillation can be totally inhibited at low concentrations. The presented results indicate that viologen-phosphorus dendrimers are able to inhibit ASN fibril formation and may be used as fibrillar regulating agents in neurodegenerative disorders.