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
• endocytóza genetika   MeSH
• ferritiny chemie   MeSH
• lékové transportní systémy metody   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
• protinádorové látky chemie   farmakokinetika   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Scaffolds modified with nanostructures are recently finding use in a broad range of applications spanning from chromatographic separations to tissue engineering. This continuation of the review series on design and applications of monolithic materials covers some of the less common monoliths including use of nanostructures in preparation, modifications, and applications.

• MeSH
• chromatografie přístrojové vybavení   metody   MeSH
• DNA izolace a purifikace   MeSH
• lidé MeSH
• nanostruktury chemie   MeSH
• peptidy izolace a purifikace   MeSH
• proteiny izolace a purifikace   MeSH
• syntetické pryskyřice chemie   MeSH
• tkáňové inženýrství přístrojové vybavení   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Many biomedical applications rely on peptide selfassembled nanostructures. One of the most promising applications among them is drug delivery. Good biocompatibility, low cost, customizable bioactivity, large drug loading capacities, chemical variety, selective targeting, and stimuli sensitive drug delivery at disease locations are just a few of the many benefits of peptide self-assembled nanostructures. Many researchers have looked into peptide self-assembled nanostructures like nanoparticles, nanotubes, nanofibers, and hydrogels for drug delivery applications. The basic mechanisms for self-assembling nanostructures based on peptides of various sorts and structures are introduced and reviewed in this review. The potential drug delivery applications of peptide self-assembled nanostructures, such as anticancer and gene drug delivery, are highlighted. Furthermore, peptide self-assembled nanostructures for drug delivery applications that are targeted and stimulus responsive.

• MeSH
• aminokyseliny * chemie   MeSH
• chemické modely MeSH
• dipeptidy * chemie   MeSH
• makromolekulární látky * chemie   MeSH
• nanostruktury MeSH
• peptidy chemie   MeSH
• proteiny chemie   MeSH
• racionální návrh léčiv * MeSH
• software MeSH

TiO2-based nanomaterials have attracted prodigious attention as a photocatalysts in numerous fields of applications. In this thematic issue, the mechanism behind the photocatalytic activity of nano-TiO2 as well as the critical properties have been reviewed in details. The synthesis routes and the variables that affect the size and crystallinity of nano-TiO2 have also been discussed in detail. Moreover, a newly emerged class of color TiO2, TiO2 in aerogel form, nanotubes form, doped and undoped form, and other forms of TiO2 have been discussed in details. Photocatalytic and photovoltaic applications and the type of nano-TiO2 that is more suitable for these applications have been discussed in this review.

• MeSH
• katalýza MeSH
• molekulární modely MeSH
• nanostruktury chemie   MeSH
• povrchové vlastnosti MeSH
• techniky syntetické chemie metody   MeSH
• titan chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In this study, we investigate the preparation of surface pattern of functional groups on poly(lactide) (PLA) surfaces through the controlled deposition of core-shell self-assemblies based on functionalized PLA-b-PEO amphiphilic block copolymers from selective solvents. Through grafting RGDS peptide onto the functionalized copolymer surface, the presented approach enables to prepare PLA surfaces with random and clustered spatial distribution of adhesive motifs. The proposed topography of the adhesion motif was proved by atomic force microscopy techniques using biotin-tagged RGDS peptide grafted on the surface and streptavidin-modified gold nanospheres which bind the tagged RGDS peptides as a contrast agent. The cell culture study under static and dynamic conditions with MG63 osteosarcoma cell line showed that the clustered distribution of RGDS peptides provided more efficient initial cell attachment and spreading, and resistance to cell detachment under dynamic culture compared to randomly distributed RGDS motif when with the same average RGDS peptide concentration.

• MeSH
• biomimetika MeSH
• buněčná adheze účinky léků   MeSH
• kovové nanočástice MeSH
• laktáty chemie   MeSH
• lidé MeSH
• mikroskopie atomárních sil MeSH
• nádorové buněčné linie MeSH
• nanostruktury chemie   MeSH
• oligopeptidy MeSH
• polyethylenglykoly chemie   MeSH
• povrchové vlastnosti MeSH
• streptavidin chemie   MeSH
• vazba proteinů MeSH
• zlato MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present work highlights recent achievements in development of nanostructured dispersions and biocolloids for drug delivery applications. We emphasize the key role of biological small-angle X-ray scattering (BioSAXS) investigations for the nanomedicine design. A focus is given on controlled encapsulation of small molecular weight phytochemical drugs in lipid-based nanocarriers as well as on encapsulation of macromolecular siRNA, plasmid DNA, peptide and protein pharmaceuticals in nanostructured nanoparticles that may provide efficient intracellular delivery and triggered drug release. Selected examples of utilisation of the BioSAXS method for characterization of various types of liquid crystalline nanoorganizations (liposome, spongosome, cubosome, hexosome, and nanostructured lipid carriers) are discussed in view of the successful encapsulation and protection of phytochemicals and therapeutic biomolecules in the hydrophobic or the hydrophilic compartments of the nanocarriers. We conclude that the structural design of the nanoparticulate carriers is of crucial importance for the therapeutic outcome and the triggered drug release from biocolloids.

• MeSH
• difrakce rentgenového záření MeSH
• fytonutrienty chemie   farmakologie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• koloidy MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• maloúhlový rozptyl MeSH
• nanočástice chemie   MeSH
• nosiče léků * MeSH
• peptidy chemie   metabolismus   MeSH
• plazmidy chemie   metabolismus   MeSH
• příprava léků metody   MeSH
• protinádorové látky chemie   farmakologie   MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery.

• MeSH
• aplikace intranazální MeSH
• biologický transport MeSH
• chitosan chemie   MeSH
• čichová sliznice cytologie   metabolismus   MeSH
• farmaceutická chemie metody   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• krysa rodu rattus MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• lékové transportní systémy * MeSH
• lipidy chemie   MeSH
• mozek metabolismus   MeSH
• nanočástice * MeSH
• nos MeSH
• nosní sliznice metabolismus   MeSH
• penetrační peptidy chemie   MeSH
• polymery chemie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.

• MeSH
• hemoxygenasa-1 MeSH
• interleukin-8 metabolismus   genetika   MeSH
• kovové nanočástice toxicita   MeSH
• lidé MeSH
• mapy interakcí proteinů * účinky léků   MeSH
• nanostruktury toxicita   MeSH
• oxid křemičitý toxicita   MeSH
• oxid zinečnatý toxicita   chemie   MeSH
• stříbro * toxicita   MeSH
• THP-1 buňky MeSH
• titan * toxicita   MeSH
• transkripční faktor ATF3 genetika   metabolismus   MeSH
• transkriptom účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A sustained effort to maximize the therapeutic effect of newly discovered active pharmaceutical ingredients (APIs) leads to the search for and development of advanced drug formulations. In this regard, a range of multicomponent and nanostructured systems that often combine the properties of solid and liquid materials have been developed. Besides the sophisticated supramolecular synthesis the development of these systems also requires in-depth view into their local architecture at atomic-resolution level. As these materials naturally exist at the borderline between the solid and liquid phases, the high-quality diffraction data are inherently unavailable. Therefore the structural description of these materials requires development of novel and highly efficient strategies. The aim of all this process is formulation of computation-experimental procedures allowing for precise characterization of the complex pharmaceutical systems including composite solids, nanocrystalline systems as well as partially ordered materials. In this regard, NMR crystallography belongs among the most successful approaches. In this contribution we report our recent achievements in characterizing atomic-resolution structure of complex pharmaceutical solids such as peptide derivatives of boronic acid, hybrid organic-inorganic liquisolid drug delivery systems, polymer-drug solid dispersions and mucoadhesive buccal films.

• Klíčová slova
• krystalové struktury,
• MeSH
• algináty chemie   MeSH
• Aspirin chemie   MeSH
• ciklopirox chemie   MeSH
• farmaceutická technologie klasifikace   MeSH
• krystalografie * metody   MeSH
• léčivé přípravky MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• nanomedicína dějiny   metody   MeSH
• polymery aplikace a dávkování   chemie   MeSH
• sloučeniny boru chemie   MeSH
• Publikační typ
• práce podpořená grantem MeSH