BACKGROUND: The emergence of antibiotic resistance in pathogenic bacteria has become a global threat, encouraging the adoption of efficient and effective alternatives to conventional antibiotics and promoting their use as replacements. Titanium dioxide nanoparticles (TiO2 NPs) have been reported to exhibit antibacterial properties. In this study, we synthesized and characterized TiO2 NPs in anatase and rutile forms with surface modification by geraniol (GER). RESULTS: The crystallinity and morphology of modified TiO2 NPs were analyzed by UV/Vis spectrophotometry, X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) with elemental mapping (EDS). The antimicrobial activity of TiO2 NPs with geraniol was assessed against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The minimum inhibitory concentration (MIC) values of modified NPs ranged from 0.25 to 1.0 mg/ml against all bacterial strains, and the live dead assay and fractional inhibitory concentration (FIC) supported the antibacterial properties of TiO2 NPs with GER. Moreover, TiO2 NPs with GER also showed a significant decrease in the biofilm thickness of MRSA. CONCLUSIONS: Our results suggest that TiO2 NPs with GER offer a promising alternative to antibiotics, particularly for controlling antibiotic-resistant strains. The surface modification of TiO2 NPs by geraniol resulted in enhanced antibacterial properties against multiple bacterial strains, including antibiotic-resistant MRSA. The potential applications of modified TiO2 NPs in the biomedical and environmental fields warrant further investigation.
Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver and kidneys before and after the application of CDDP and platinum nanoparticles (PtNPs-10 and PtNPs-40). The treatment of the liver with the selected drugs affected different amino acids; however, Leu and Arg were decreased after all treatments. The treatment of the kidneys with CDDP mostly affected Val; PtNPs-10 decreased Val, Ile and Thr; and PtNPs-40 affected only Pro. In addition, we tested the same drugs on two healthy cell lines, HaCaT and HEK-293, and ultimately explored the amino acid profiles in relation to the tricarboxylic acid cycle (TCA) and methionine cycle, which revealed that in both cell lines, there was a general increase in amino acid concentrations associated with changes in the concentrations of the metabolites of these cycles.
- Publikační typ
- časopisecké články MeSH
Purpose: The chick chorioallantoic membrane (CAM) assay can provide an alternative versatile, cost-effective, and ethically less controversial in vivo model for reliable screening of drugs. In the presented work, we demonstrate that CAM assay (in ovo and ex ovo) can be simply employed to delineate the effects of cisplatin (CDDP) and ellipticine (Elli) on neuroblastoma (Nbl) cells in terms of their growth and metastatic potential. Methods: The Nbl UKF-NB-4 cell line was established from recurrent bone marrow metastases of high-risk Nbl (stage IV, MYCN amplification, 7q21 gain). Ex ovo and in ovo CAM assays were optimized to evaluate the antimetastatic activity of CDDP and Elli. Immunohistochemistry, qRT-PCR, and DNA isolation were performed. Results: Ex ovo CAM assay was employed to study whether CDDP and Elli exhibit any inhibitory effects on growth of Nbl xenograft in ex ovo CAM assay. Under the optimal conditions, Elli and CDDP exhibited significant inhibition of the size of the primary tumor. To study the efficiency of CDDP and Elli to inhibit primary Nbl tumor growth, intravasation, and extravasation in the organs, we adapted the in ovo CAM assay protocol. In in ovo CAM assay, both studied compounds (CDDP and Elli) exhibited significant (p < 0.001) inhibitory activity against extravasation to all investigated organs including distal CAM. Conclusions: Taken together, CAM assay could be a helpful and highly efficient in vivo approach for high-throughput screening of libraries of compounds with expected anticancer activities.
- Publikační typ
- časopisecké články MeSH
Purpose: The present study deals with the in vitro evaluation of the potential use of coordination compound-based zinc oxide (ZnO) nanoparticles (NPs) for the treatment of triple negative breast cancer cells (TNBrCa). As BrCa is one of the most prevalent cancer types and TNBrCa treatment is difficult due to poor prognosis and a high metastasis rate, finding a more reliable treatment option should be of the utmost interest. Methods: Prepared by reacting zinc carboxylates (formate, acetate, propionate, butyrate, isobutyrate, valerate) and hexamethylenetetramine, 4 distinct coordination compounds were further subjected to two modes of conversion into ZnO NPs - ultrasonication with oleic acid or heating of pure precursors in an air atmosphere. After detailed characterization, the resulting ZnO NPs were subjected to in vitro testing of cytotoxicity toward TNBrCa and normal breast epithelial cells. Further, their biocompatibility was evaluated. Results: The resulting ZnO NPs provide distinct morphological features, size, biocompatibility, and selective cytotoxicity toward TNBrCa cells. They internalize into two types of TNBrCa cells and imbalance their redox homeostasis, influencing their metabolism, morphology, and ultimately leading to their death via apoptosis or necrosis. Conclusion: The crucial properties of ZnO NPs seem to be their morphology, size, and zinc content. The ZnO NPs with the most preferential values of all three properties show great promise for a future potential use in the therapy of TNBrCa.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- oxid zinečnatý chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- triple-negativní karcinom prsu patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Introduction: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system. Methods: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin´s quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities. Results: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs' structural and functional properties. Conclusion: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.
- MeSH
- antitumorózní látky farmakologie MeSH
- biokompatibilní materiály chemie MeSH
- buněčná smrt účinky léků MeSH
- buněčné klony MeSH
- buněčné linie MeSH
- chinazoliny chemie farmakologie MeSH
- chinoliny chemie farmakologie MeSH
- difuze MeSH
- fenylmočovinové sloučeniny chemie farmakologie MeSH
- ferritin chemie MeSH
- inhibitory proteinkinas farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- koně MeSH
- kyselina listová chemie MeSH
- lidé MeSH
- nosiče léků chemie MeSH
- piperidiny chemie farmakologie MeSH
- pohyb buněk účinky léků MeSH
- povrchové vlastnosti MeSH
- systémy cílené aplikace léků * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule's ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.
- MeSH
- algináty chemie MeSH
- antigeny CD31 metabolismus MeSH
- chitosan chemie MeSH
- doxorubicin aplikace a dávkování farmakokinetika MeSH
- HEK293 buňky MeSH
- hemolýza účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanokapsle aplikace a dávkování chemie toxicita MeSH
- peptidy chemie metabolismus MeSH
- polyelektrolyty chemie MeSH
- rostlinné gumy chemie MeSH
- systémy cílené aplikace léků metody MeSH
- testy toxicity MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
An inexorable switch from antibiotics has become a major desideratum to overcome antibiotic resistance. Bacteriocin from Lactobacillus casei, a cardinal probiotic was used to design novel antibacterial peptides named as Probiotic Bacteriocin Derived and Modified (PBDM) peptides (PBDM1: YKWFAHLIKGLC and PBDM2: YKWFRHLIKKLC). The loop-shaped 3D structure of peptides was characterized in silico via molecular dynamics simulation as well as biophysically via spectroscopic methods. Thereafter, in vitro results against multidrug resistant bacterial strains and hospital samples demonstrated the strong antimicrobial activity of PBDM peptides. Further, in vivo studies with PBDM peptides showed downright recovery of balb/c mice from Vancomycin Resistant Staphylococcus aureus (VRSA) infection to its healthy condition. Thereafter, in vitro study with human epithelial cells showed no significant cytotoxic effects with high biocompatibility and good hemocompatibility. In conclusion, PBDM peptides displayed significant antibacterial activity against certain drug resistant bacteria which cause infections in human beings. Future analysis are required to unveil its mechanism of action in order to execute it as an alternative to antibiotics.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Currently, the diagnosis and treatment of neuroblastomas-the most frequent solid tumors in children-exploit the norepinephrine transporter (hNET) via radiolabeled norepinephrine analogs. We aim to develop a nanomedicine-based strategy towards precision therapy by targeting hNET cell-surface protein with hNET-derived homing peptides. RESULTS: The peptides (seq. GASNGINAYL and SLWERLAYGI) were shown to bind high-resolution homology models of hNET in silico. In particular, one unique binding site has marked the sequence and structural similarities of both peptides, while most of the contribution to the interaction was attributed to the electrostatic energy of Asn and Arg (< - 228 kJ/mol). The peptides were comprehensively characterized by computational and spectroscopic methods showing ~ 21% β-sheets/aggregation for GASNGINAYL and ~ 27% α-helix for SLWERLAYGI. After decorating 12-nm ferritin-based nanovehicles with cysteinated peptides, both peptides exhibited high potential for use in actively targeted neuroblastoma nanotherapy with exceptional in vitro biocompatibility and stability, showing minor yet distinct influences of the peptides on the global expression profiles. Upon binding to hNET with fast binding kinetics, GASNGINAYLC peptides enabled rapid endocytosis of ferritins into neuroblastoma cells, leading to apoptosis due to increased selective cytotoxicity of transported payload ellipticine. Peptide-coated nanovehicles significantly showed higher levels of early apoptosis after 6 h than non-coated nanovehicles (11% and 7.3%, respectively). Furthermore, targeting with the GASNGINAYLC peptide led to significantly higher degree of late apoptosis compared to the SLWERLAYGIC peptide (9.3% and 4.4%, respectively). These findings were supported by increased formation of reactive oxygen species, down-regulation of survivin and Bcl-2 and up-regulated p53. CONCLUSION: This novel homing nanovehicle employing GASNGINAYLC peptide was shown to induce rapid endocytosis of ellipticine-loaded ferritins into neuroblastoma cells in selective fashion and with successful payload. Future homing peptide development via lead optimization and functional analysis can pave the way towards efficient peptide-based active delivery of nanomedicines to neuroblastoma cells.
- MeSH
- antitumorózní látky chemie farmakokinetika farmakologie MeSH
- endocytóza genetika MeSH
- ferritin chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanomedicína MeSH
- nanostruktury chemie MeSH
- neuroblastom metabolismus MeSH
- peptidy chemie genetika metabolismus MeSH
- proteiny přenášející noradrenalin přes plazmatickou membránu * chemie genetika metabolismus MeSH
- systémy cílené aplikace léků metody MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The current epidemic of antibiotic-resistant infections urges to develop alternatives to less-effective antibiotics. To assess anti-bacterial potential, a novel coordinate compound (RU-S4) was synthesized using ruthenium-Schiff base-benzimidazole ligand, where ruthenium chloride was used as the central atom. RU-S4 was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman spectroscopy. Antibacterial effect of RU-S4 was studied against Staphylococcus aureus (NCTC 8511), vancomycin-resistant Staphylococcus aureus (VRSA) (CCM 1767), methicillin-resistant Staphylococcus aureus (MRSA) (ST239: SCCmecIIIA), and hospital isolate Staphylococcus epidermidis. The antibacterial activity of RU-S4 was checked by growth curve analysis and the outcome was supported by optical microscopy imaging and fluorescence LIVE/DEAD cell imaging. In vivo (balb/c mice) infection model prepared with VRSA (CCM 1767) and treated with RU-S4. In our experimental conditions, all infected mice were cured. The interaction of coordination compound with bacterial cells were further confirmed by cryo-scanning electron microscope (Cryo-SEM). RU-S4 was completely non-toxic against mammalian cells and in mice and subsequently treated with synthesized RU-S4.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Bacteria účinky léků MeSH
- buněčné linie MeSH
- komplexní sloučeniny chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- myši MeSH
- Ramanova spektroskopie MeSH
- ruthenium chemie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Recently, the interest is increasing to find alternatives to replace the usage of antibiotics since their massive and improper usage enhance the antibiotic resistance in human pathogens. In this study, for the first time we showed that the soil proteins have very high antibacterial activity (98% of growth inhibition) against methicillin resistant Staphylococcus aureus (MRSA), one of the most threatening human pathogens. We found that the protein extract (C3) from the forest with past intensive management showed higher antibacterial activity than that of unmanaged forest. The MIC and IC50 were found to be 30 and 15.0 μg protein g-1 dry soil respectively. C3 was found to kill the bacteria by cell wall disruption and genotoxicity which was confirmed by optical and fluorescent microscopy and comet assay. According to qPCR study, the mecA (the antibiotic resistant gene) expression in MRSA was found to be down-regulated after C3 treatment. In contrast, C3 showed no hemolytic toxicity on human red blood cells which was confirmed by hemolytic assay. According to ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), 144 proteins were identified in C3 among which the majority belonged to Gram negative bacteria (45.8%). Altogether, our results will help to develop novel, cost-effective, non-toxic and highly efficient antibacterial medicines from natural sources against antibiotic resistant infections.
