INTRODUCTION AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the nasal cavity, penetrates the nasal epithelial cells through the interaction of its spike protein with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and then triggers a cytokine storm. We aimed to assess the biocompatibility of fullerenol nanoparticles C60(OH)40 and ectoine, and to document their effect on the protection of primary human nasal epithelial cells (HNEpCs) against the effects of interaction with the fragment of virus - spike protein. This preliminary research is the first step towards the construction of a intranasal medical device with a protective, mechanical function against SARS-CoV-2 similar to that of personal protective equipment (eg masks). METHODS: We used HNEpCs and the full-length spike protein from SARS-CoV-2 to mimic the first stage of virus infection. We assessed cell viability with the XTT assay and a spectrophotometer. May-Grünwald Giemsa and periodic acid-Schiff staining served to evaluate HNEpC morphology. We assessed reactive oxygen species (ROS) production by using 2',7'-dichlorofluorescin diacetate and commercial kit. Finally, we employed reverse transcription polymerase chain reaction, Western blotting and confocal microscopy to determine the expression of angiotensin-converting enzyme 2 (ACE2) and inflammatory cytokines. RESULTS: There was normal morphology and unchanged viability of HNEpCs after incubation with 10 mg/L C60(OH)40, 0.2% ectoine or their composite for 24 h. The spike protein exerted cytotoxicity via ROS production. Preincubation with the composite protected HNEpCs against the interaction between the spike protein and the host membrane and prevented the production of key cytokines characteristic of severe coronavirus disease 2019, including interleukin 6 and 8, monocyte chemotactic protein 1 and 2, tissue inhibitor of metalloproteinases 2 and macrophage colony-stimulating factor. CONCLUSION: In the future, the combination of fullerenol and ectoine may be used to prevent viral infections as an intranasal medical device for people with reduced immunity and damaged mucous membrane.

• Klíčová slova
• ACE2, cytokine storm, ectoine, nasal epithelium, polyhydroxylated fullerene, spike,
• MeSH
• aminokyseliny diaminové MeSH
• angiotensin-konvertující enzym 2 metabolismus   MeSH
• COVID-19 * prevence a kontrola   MeSH
• cytokiny metabolismus   MeSH
• epitelové buňky * účinky léků   virologie   MeSH
• fullereny * farmakologie   chemie   MeSH
• glykoprotein S, koronavirus * metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• nanočástice * chemie   MeSH
• nosní sliznice účinky léků   cytologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• SARS-CoV-2 * účinky léků   MeSH
• syndrom uvolnění cytokinů * prevence a kontrola   MeSH
• viabilita buněk * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny diaminové MeSH
• angiotensin-konvertující enzym 2 MeSH
• cytokiny MeSH
• ectoine MeSH Prohlížeč
• fullerenol MeSH Prohlížeč
• fullereny * MeSH
• glykoprotein S, koronavirus * MeSH
• reaktivní formy kyslíku MeSH
• spike protein, SARS-CoV-2 MeSH Prohlížeč

The unique potential of fullerene C60 for various biological applications has ignited significant interest. However, its inherent non-polarity poses a critical challenge for its effective integration within biological systems. This study delves into the intricate physicochemical characteristics of the innovative [C60 + NO] complex using density functional theory and time-dependent density functional theory. The computational analyses encompass molecular charge, surface electrostatic potential, and dipole moment evaluations. Impressively, the dipole moment of the [C60 + NO] complex significantly increases to 12.92 D. Meticulous surface analysis reveals a subtle interplay between molecular structures, indicating weak interactions. The analysis of the absorption spectrum unveils a noteworthy red-shift of 200 nm subsequent to complex formation. To elucidate the electron transfer mechanisms, we explore photo-induced electron transfer through CAM-B3LYP. This exploration elucidates intricate pathways governing electron transfer, with complementary insights gleaned from Marcus theory's outputs, especially the Gibbs free energy of electron transfer. Changes in the physicochemical properties of approaching C60 and NO molecules reveal interesting results compared to separate molecules. These findings resonate profoundly in the context of potential biological and pharmaceutical utilization. With implications for the biomedical area, the outcomes linked to the [C60 + NO] complex kindle optimism for pioneering biomedical applications.

• MeSH
• fullereny * chemie   MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• oxid dusnatý MeSH
• transport elektronů MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fullereny * MeSH
• oxid dusnatý MeSH

Cellular localization of carbon nanomaterials in cancer cells is essential information for better understanding their interaction with biological targets and a crucial factor for further evaluating their biological properties as nanovehicles or nanotherapeutics. Recently, increasing efforts to develop promising fullerene nanotherapeutics for cancer nanotechnology have been made. However, the main challenge regarding studying their cellular effects is the lack of effective methods for their visualization and determining their cellular fate due to the limited fluorescence of buckyball scaffolds. Herein, we developed a method for cellular localization of nonfluorescent and water-soluble fullerene nanomaterials using the in vitro click chemistry approach. First, we synthesized a triple-bonded fullerene probe (TBC60ser), which was further used as a starting material for 1,3-dipolar cycloaddition using 3-azido-7-hydroxycoumarin and sulfo-cyanine5 azide fluorophores to create fluorescent fullerene triazoles. In this work, we characterized the structurally triple-bonded [60]fullerene derivative and confirmed its high symmetry (Th) and the successful formation of fullerene triazoles by spectroscopic techniques (i.e., ultraviolet-visible, fluorescence, and Fourier transform infrared spectroscopies) and mass spectrometry. The created fluorescent fullerene triazoles were successfully localized in the MCF-7 breast cancer cell line using fluorescent microscopy. Overall, our findings demonstrate that TBC60ser localizes in the lysosomes of MCF-7 cells, with only a small affinity to mitochondria.

• Klíčová slova
• [60]fullerenes, breast cancer, cellular colocalization, click reactions, lysosomes, triazoles,
• MeSH
• fullereny * chemie   farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádory prsu * farmakoterapie   MeSH
• nanostruktury * chemie   MeSH
• triazoly MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fullereny * MeSH
• triazoly MeSH

Doxorubicin (DOX) is one of the most frequently used anticancer drugs in breast cancer treatment. However, clinical applications of DOX are restricted, largely due to the fact that its action disturbs the pro/antioxidant balance in both cancerous and non-cancerous cells. The aim of this study was to investigate the influence of fullerene (C60) in cell treatment by DOX on the proliferation of human breast cancer cells (MCF-7), concentration of metallothionein (MT) and superoxide dismutase (SOD), and SOD activity in these cells. The use of C60 in complexes with DOX causes a change in the level of cell proliferation of about 5% more than when caused by DOX alone (from 60⁻65% to 70%). The use of C60 as a DOX nanotransporter reduced the MT level increase induced by DOX. C60 alone caused an increase of SOD1 concentration. On the other hand, it led to a decrease of SOD activity. C60 in complex with DOX caused a decrease of the DOX-induced SOD activity level. Exposure of MCF-7 cells to DOX-C60 complexes results in a decrease in viable cells and may become a new therapeutic approach to breast cancer. The effects of C60 in complexes with DOX on MCF-7 cells included a decreased enzymatic (SOD activity) and nonenzymatic (MT) antioxidant status, thus indicating their prooxidant role in MCF-7 cells.

• Klíčová slova
• breast tumors, doxorubicin, drug delivery systems, fullerene, nanoparticles, metallothionein, superoxide dismutase,
• MeSH
• doxorubicin farmakologie   MeSH
• fullereny chemie   MeSH
• lidé MeSH
• metalothionein metabolismus   MeSH
• MFC-7 buňky MeSH
• nanočástice chemie   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• superoxiddismutasa 1 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin MeSH
• fullereny MeSH
• metalothionein MeSH
• protinádorové látky MeSH
• SOD1 protein, human MeSH Prohlížeč
• superoxiddismutasa 1 MeSH

The clinical use of doxorubicin (DOX) is limited by dose-related cardiomyopathy, which becomes more prevalent with increasing cumulative doses of the drug. Complexes of fullerene with DOX were designed and studied using biophysical methods. The ability of DOX to release from fullerene at different pHs was analyzed. It has been shown that the size of the fullerene-DOX complexes was ∼280 nm. The zeta potential for fullerene was -30 mV, for DOX -8 mV, and for fullerene-DOX conjugates -24 mV. Drug release was studied by CE with LIF detection. When fullerene-DOX conjugates were separated in a pH 7.5 buffer, 43% of all DOX signals were derived from free DOX, with the signal increasing as pH decreased. At pH 5.25, all DOX had been released and 100% of the signal was derived from free DOX. The release of DOX from complexes with fullerene at lower pH can be used in targeted antineoplastic therapy, resulting in lower toxicity for less acidic non-target tissue.

• Klíčová slova
• Breast tumors, Doxorubicin, Drug delivery systems, Fullerene, Nanomedicine,
• MeSH
• doxorubicin terapeutické užití   MeSH
• elektroforéza kapilární MeSH
• fluorescenční barviva chemie   MeSH
• fullereny chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádory prsu farmakoterapie   MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• optické zobrazování MeSH
• povrchové vlastnosti MeSH
• protinádorová antibiotika terapeutické užití   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• doxorubicin MeSH
• fluorescenční barviva MeSH
• fullereny MeSH
• nosiče léků MeSH
• protinádorová antibiotika MeSH

Relative concentrations of six isomeric Eu@C 72 -one based on the IPR C 72 cage (i.e., obeying the isolated-pentagon rule, IPR), two cages with a pentagon-pentagon junction (symmetries C 2 and C 2 v ), a cage with one heptagon, a cage with two heptagons, and a cage with two pentagon-pentagon fusions-are DFT computed using the Gibbs energy in a broad temperature interval. It is shown that the two non-IPR isomers with one pentagon-pentagon junction prevail at any relevant temperature and exhibit comparable populations. The IPR-satisfying structure is disfavored by both energy and entropy.

• Klíčová slova
• metallofullerenes, non-IPR fullerenes, relative populations of isomers,
• MeSH
• fullereny chemie   MeSH
• isomerie MeSH
• molekulární modely MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fullereny MeSH

Here, we propose five fullerene (C60) derivatives as new drugs against Alzheimer's disease (AD). These compounds were designed to act as new human acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII) binding site. Docking and molecular dynamic results show that our proposals bind to the HssAChE tunnel entrance, forming stable complex, and further binding free energy calculations suggest that three of the derivatives proposed here could be potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72, Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the drug design of new inhibitors of HssAChE based on C60 derivatives. Results presented here report for the first time by a new class of molecules that can become effective drugs against AD.

• Klíčová slova
• AChE inhibition, Alzheimer’s disease, docking, fullerene derivatives, molecular modeling, theoretical methodologies,
• MeSH
• acetylcholinesterasa chemie   metabolismus   MeSH
• cholinesterasové inhibitory chemie   metabolismus   farmakologie   MeSH
• fullereny chemie   metabolismus   farmakologie   MeSH
• molekulární konformace * MeSH
• molekulární modely * MeSH
• racionální návrh léčiv MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• fullerene C60 MeSH Prohlížeč
• fullereny MeSH

The computational simulation of photo-induced processes in large molecular systems is a very challenging problem. Firstly, to properly simulate photo-induced reactions the potential energy surfaces corresponding to excited states must be appropriately accessed; secondly, understanding the mechanisms of these processes requires the exploration of complex configurational spaces and the localization of conical intersections; finally, photo-induced reactions are probability events, that require the simulation of hundreds of trajectories to obtain the statistical information for the analysis of the reaction profiles. Here, we present a detailed description of our implementation of a molecular dynamics with electronic transitions algorithm within the local-orbital density functional theory code FIREBALL, suitable for the computational study of these problems. As an example of the application of this approach, we also report results on the [2 + 2] cycloaddition of ethylene with maleic anhydride and on the [2 + 2] photo-induced polymerization reaction of two C60 molecules. We identify different deactivation channels of the initial electron excitation, depending on the time of the electronic transition from LUMO to HOMO, and the character of the HOMO after the transition.

• MeSH
• algoritmy MeSH
• elektronika * MeSH
• elektrony MeSH
• ethyleny chemie   MeSH
• fullereny chemie   MeSH
• kvantová teorie * MeSH
• maleinanhydridy chemie   MeSH
• molekulární modely MeSH
• počítačová simulace MeSH
• simulace molekulární dynamiky * MeSH
• světlo * MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ethylene MeSH Prohlížeč
• ethyleny MeSH
• fullerene C60 MeSH Prohlížeč
• fullereny MeSH
• maleinanhydridy MeSH

Although a non-IPR fullerene cage is common for endohedral cluster fullerenes, it is very rare for conventional endofullerenes M@C2n, probably because of the minimum geometry fit effect of the endohedral single metal ion. In this work, we report on a new non-IPR endofullerene Sm@C2v(19138)-C76, including its structural and electrochemical features. A combined study of single-crystal X-ray diffraction and DFT calculations not only elucidates the non-IPR cage structure of C2v(19138)-C76 but also suggests that the endohedral Sm(2+) ion prefers to reside along the C2 cage axis and close to the fused pentagon unit in the cage framework, indicative of a significant metal-cage interaction, which alone can stabilize the non-IPR cage. Furthermore, electrochemical studies reveal the fully reversible redox behaviors and small electrochemical gap of Sm@C2v(19138)-C76, which are comparable to those of IPR species Sm@D3h-C74.

• MeSH
• elektrochemické techniky MeSH
• fullereny chemie   MeSH
• isomerie MeSH
• kationty dvojmocné MeSH
• krystalografie rentgenová MeSH
• kvantová teorie MeSH
• molekulární struktura MeSH
• nikl chemie   MeSH
• oxidace-redukce MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fullereny MeSH
• kationty dvojmocné MeSH
• nikl MeSH

Thin films of binary C60/Ti composites, with various concentrations of Ti ranging from ~ 25% to ~ 70%, were deposited on microscopic glass coverslips and were tested for their potential use in bone tissue engineering as substrates for the adhesion and growth of bone cells. The novelty of this approach lies in the combination of Ti atoms (i.e., widely used biocompatible material for the construction of stomatological and orthopedic implants) with atoms of fullerene C60, which can act as very efficient radical scavengers. However, fullerenes and their derivatives are able to generate harmful reactive oxygen species and to have cytotoxic effects. In order to stabilize C60 molecules and to prevent their possible cytotoxic effects, deposition in the compact form of Ti/C60 composites (with various Ti concentrations) was chosen. The reactivity of C60/Ti composites may change in time due to the physicochemical changes of molecules in an air atmosphere. In this study, we therefore tested the dependence between the age of C60/Ti films (from one week to one year) and the adhesion, morphology, proliferation, viability, metabolic activity and potential DNA damage to human osteosarcoma cells (lines MG-63 and U-2 OS). After 7 days of cultivation, we did not observe any negative influence of fresh or aged C60/Ti layers on cell behavior, including the DNA damage response. The presence of Ti atoms resulted in improved properties of the C60 layers, which became more suitable for cell cultivation.

• MeSH
• buněčná adheze účinky léků   MeSH
• časové faktory MeSH
• fullereny chemie   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteoblasty cytologie   účinky léků   metabolismus   MeSH
• poškození DNA MeSH
• proliferace buněk účinky léků   MeSH
• reaktivní formy kyslíku antagonisté a inhibitory   metabolismus   MeSH
• titan chemie   farmakologie   MeSH
• tkáňové inženýrství MeSH
• tkáňové podpůrné struktury * MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fullerene C60 MeSH Prohlížeč
• fullereny MeSH
• reaktivní formy kyslíku MeSH
• titan MeSH