Nanoparticles exist for a long time as both inorganic and organic parts of nature. Recently, massive expansion of nanotechnologies is evidenced, together with intentional production of new nanoparticles which have not been in contact with living organisms until now. Besides obvious positive aspects, potential threats related to their exposure should be taken into consideration. Unique physical-chemical properties of nanoparticles cause a high bioactivity following their intake (through air, ingestion and skin) and unrestricted spread in exposed organs. Primary effects of nanoparticles on cellular level represent oxidative stress and reactions leading to apoptosis, autophagocytosis and necrosis. Number of studies indicating contribution of nanoparticles to numerous disorders has been recently increasing. However, detailed mechanisms of health effects are not well known. Similarly, there is insufficient information on life cycle of nanoparticles in the environment. Research in this field as well as legislation is behind rapid development and use of nanotechnologies. Considering absence of mandatory exposure limits and other protective measures, nanomaterials represent a potential threat for population health. Recommendations and guidelines of international institutions can contribute to deal with situation, however, passing of effective legislation both on national and European level is urgently needed.

• MeSH
• lidé MeSH
• nanostruktury škodlivé účinky   chemie   MeSH
• pracovní expozice škodlivé účinky   MeSH
• veřejné zdravotnictví * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

The functionalization of nanomaterials with suitable capping ligands or bioactive agents is an interesting strategy in designing nanosystems with suitable applicability and biocompatibility; the physicochemical and biological properties of these nanomaterials can be highly improved for biomedical applications. In this context, numerous explorations have been conducted in the functionalization of silver (Ag) and gold (Au) nanomaterials using suitable functional groups or agents to design nanosystems with unique physicochemical properties such as excellent biosensing capabilities, biocompatibility, targeting features, and multifunctionality for biomedical purposes. Future studies should be undertaken for designing novel functionalization tactics to improve the properties of Au- and Ag-based nanosystems and reduce their toxicity. The possible release of cytotoxic radicals or ions, the internalization of nanomaterials, the alteration of cellular signaling pathways, the translocation of these nanomaterials across the cell membranes into mitochondria, DNA damages, and the damage of cell membranes are the main causes of their toxicity, which ought to be comprehensively explored. In this study, recent advancements in diagnostic and therapeutic applications of functionalized Au and Ag nanomaterials are deliberated, focusing on important challenges and future directions.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The combination of different nanomaterials has been investigated during the past few decades and represents an exciting challenge for the unexpected emerging properties of the resulting nano-hybrids. Spermidine (Spd), a biogenic polyamine, has emerged as a useful functional monomer for the development of carbon quantum dots (CQDs). Herein, an electrostatically stabilized ternary hybrid, constituted of iron oxide-DNA (the core) and spermidine carbon quantum dots (CQDSpds, the shell), was self-assembled and fully characterized. The as-obtained nano-hybrid was tested on HeLa cells to evaluate its biocompatibility as well as cellular uptake. Most importantly, besides being endowed by the magnetic features of the core, it displayed drastically enhanced fluorescence properties in comparison with parent CQDSpds and it is efficiently internalized by HeLa cells. This novel ternary nano-hybrid with multifaceted properties, ranging from fluorescence to superparamagnetism, represents an interesting option for cell tracking.

• MeSH
• biotechnologie MeSH
• fluorescence MeSH
• HeLa buňky MeSH
• kvantové tečky chemie   metabolismus   MeSH
• lidé MeSH
• nanostruktury chemie   MeSH
• polyaminy chemie   metabolismus   MeSH
• statická elektřina MeSH
• uhlík chemie   metabolismus   MeSH
• železité sloučeniny chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Fluorescent nanodiamonds (NDs) attracted attention as a new promising type of nanoparticles for bioapplications. This carbon nanomaterial with low-toxicity is able to accommodate fluorescent nitrogen-vacancy (N-V) color centers, prime examples of non-photobleachable defects of diamond crystal lattice. An overview of ND applications in bioimaging is presented. NDs are compared with other fluorescent probes and their specific chemical and colloidal properties were shown. The biologically relevant properties of fluorescent NDs such as toxicity, biocompatibility and their cellular localization and internalization are discussed.

• MeSH
• cílená molekulární terapie využití   MeSH
• fluorescence * MeSH
• fluorescenční barviva chemie   MeSH
• lékové transportní systémy využití   MeSH
• lidé MeSH
• luminiscence MeSH
• molekulární sondy - techniky MeSH
• molekulární zobrazování * MeSH
• nanodiamanty * chemie   MeSH
• nanostruktury MeSH
• Ramanova spektroskopie MeSH
• receptory umělé * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Bio-nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies and reduce systemic toxicity. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency, different nanomaterials have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting, requires a deeper understanding of the biological phenomena underlying cell-nanoparticle interactions. In this context, we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially enhancing nanotherapy specificity.

• MeSH
• adaptorové proteiny signální transdukční metabolismus   MeSH
• buněčný převod mechanických signálů účinky léků   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   MeSH
• nanomedicína MeSH
• signální dráha Hippo MeSH
• signální proteiny YAP MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Chemoterapie nádorových onemocnění je často komplikována toxickými vedlejšími účinky cytostatik na zdravé tkáně. Nově navrhované „chytré“ lékové transportní systémy by měly ochránit zdravé buňky před působením léčiva a po dosažení svého cíle – nemocného orgánu nebo tkáně – obsažené léčivo uvolnit jako odpověď na specifický podnět. Spouštěcí mechanismus může být uvnitř buňky (např. místní změna pH) nebo může být externí (např. vnější aplikace zvýšené teploty, magnetického či elektromagnetického pole nebo ultrazvuku). Ideu „magických kuliček“, které procházejí zdravými tkáněmi a zasahují nemocná místa (např. nádory), poprvé vyslovil zakladatel chemoterapie Paul Ehrlich na počátku 20. století. Avšak i po uplynutí sta let zůstává jejich praktické využití na počátku své cesty.

Cancer chemotherapy is often complicated by toxic side effects of the free drug on healthy tissues. New „smart“ drug delivery systems are designed to protect the healthy cells from the drug until it reaches the target diseased organ or tissue to be released in response to a specific stimulus or trigger. The trigger mechanism may be internal to the cell (e.g. a local change of pH) or external (e.g. a pplication of increased temperature, magnetic/electromagnetic field or ultrasound). The idea of a „magic bullet“ that bypasses healthy tissues and hits a diseased target (e.g. a tumor) was first dreamed by Paul Ehrlich, the founder of chemotherapy, at the down of the twentieth century. However, even after a century, putting his idea into practice still remains a major challenge.

• MeSH
• lékové transportní systémy MeSH
• liposomy MeSH
• nádory farmakoterapie   MeSH
• nanomedicína MeSH
• nanostruktury MeSH
• nosiče léků MeSH
• protinádorové látky aplikace a dávkování   MeSH

Ritonavir (RIT) is a widely used antiviral drug that acts as an HIV protease inhibitor with emerging potential in anticancer therapies. RIT causes inhibition of P-glycoprotein, which plays an important role in multidrug resistance (MDR) in cancer cells when overexpressed. Moreover, RIT causes mitochondrial dysfunction, leading to decreased ATP production and reduction of caveolin I expression, which can affect cell migration and tumor progression. To increase its direct antitumor activity, decrease severe side effects induced by the use of free RIT and improve its pharmacokinetics, ritonavir 5-methyl-4-oxohexanoate (RTV) was synthesized and conjugated to a tumor-targeted polymer carrier based on a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. Here we demonstrated that polymer-bound RTV enhanced the internalization of polymer-RTV conjugates, differing in RTV content from 4 to 15 wt%, in HeLa cancer cells compared with polymer without RTV. The most efficient influx and internalization properties were determined for the polymer conjugate bearing 11 wt% of RTV. This conjugate was internalized by cells using both caveolin- and clathrin-dependent endocytic pathways in contrast to the RTV-free polymer, which was preferentially internalized only by clathrin-mediated endocytosis. Moreover, we found the co-localization of the RTV-conjugate with mitochondria and a significant decrease of ATP production in treated cells. Thus, the impact on mitochondrial mechanism can influence the function of ATP-dependent P-glycoprotein and also the cell viability of MDR cancer cells. Overall, this study demonstrated that the polymer-RTV conjugate is a promising polymer-based nanotherapeutic, suitable for antitumor combination therapy with other anticancer drugs and a potential mitochondrial drug delivery system.

• MeSH
• adenosintrifosfát biosyntéza   MeSH
• chemorezistence účinky léků   MeSH
• endocytóza účinky léků   MeSH
• HeLa buňky MeSH
• kaveolin 1 biosyntéza   genetika   MeSH
• klathrin farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• methakryláty chemie   MeSH
• nanostruktury chemie   MeSH
• P-glykoprotein účinky léků   metabolismus   MeSH
• polymery MeSH
• protinádorové látky aplikace a dávkování   chemie   MeSH
• ritonavir aplikace a dávkování   analogy a deriváty   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Nanomaterials are currently the subject of intense research due to their wide variety of potential applications in the biomedical, optical and electronic fields. We prepared and tested cobalt zinc ferrite nanoparticles (Co0.5Zn0.5Fe2O4+γ [CZF-NPs]) encapsulated by amorphous silica in order to find a safe contrast agent and magnetic label for tracking transplanted cells within an organism using magnetic resonance imaging (MRI). Rat mesenchymal stem cells (rMSCs) were labeled for 48 h with a low, medium or high dose of CZF-NPs (0.05; 0.11 or 0.55 mM); silica NPs (Si-NPs; 0.11 mM) served as a positive control. The internalization of NPs into cells was verified by transmission electron microscopy. Biological effects were analyzed at the end of exposure and after an additional 72 h of cell growth without NPs. Compared to untreated cells, Annexin V/Propidium Iodide labeling revealed no significant cytotoxicity for any group of treated cells and only a high dose of CZF-NPs slowed down cell proliferation and induced DNA damage, manifested as a significant increase of DNA-strand breaks and oxidized DNA bases. This was accompanied by high concentrations of 15-F2t-isoprostane and carbonyl groups, demonstrating oxidative injury to lipids and proteins, respectively. No harmful effects were detected in cells exposed to the low dose of CZF-NPs. Nevertheless, the labeled cells still exhibited an adequate relaxation rate for MRI in repeated experiments and ICP-MS confirmed sufficient magnetic label concentrations inside the cells. The results suggest that the silica-coated CZF-NPs, when applied at a non-toxic dose, represent a promising contrast agent for cell labeling.

• MeSH
• barvení a značení MeSH
• buněčné kultury MeSH
• isoprostany metabolismus   MeSH
• karbonylace proteinů účinky léků   MeSH
• kobalt chemie   toxicita   MeSH
• kontrastní látky chemie   toxicita   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• magnetická rezonanční tomografie MeSH
• metabolismus lipidů účinky léků   MeSH
• mezenchymální kmenové buňky účinky léků   metabolismus   ultrastruktura   MeSH
• nanočástice chemie   toxicita   MeSH
• oxid křemičitý chemie   toxicita   MeSH
• poškození DNA * MeSH
• povrchové vlastnosti MeSH
• proliferace buněk účinky léků   MeSH
• sloučeniny zinku chemie   toxicita   MeSH
• transmisní elektronová mikroskopie MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• železité sloučeniny chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The application of nanotechnology in tissue engineering is an emerging and rapidly growing area of research. The advances of nanotechnology can bring additional functionality to vascular scaffolds and optimize internal vascular graft surface. Metals and their salts are used for their antibacterial effects, Ag(I) and Cu(II) ions ranking among the most studied ones. Recently antibacterial effects of Pt, Pd and Rh have also been demostrated. Natural polymers are also suitable for modification and improvement of the properties of vascular grafts, chitosan and hyaluronic acid being their main representatives. In addition to antimicrobial effects they support cells endothelisation and increase vascular permeability.

• MeSH
• biokompatibilní materiály MeSH
• biotechnologie * metody   MeSH
• cévní protézy * trendy   MeSH
• chitosan MeSH
• elastin MeSH
• katetrizace * MeSH
• katétry MeSH
• kolagen MeSH
• kovové nanočástice * využití   MeSH
• kyselina hyaluronová MeSH
• lidé MeSH
• nanostruktury využití   MeSH
• nanotechnologie * metody   MeSH
• nanovlákna MeSH
• průchodnost cév * MeSH
• tkáňové inženýrství * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Dendritic poly(L-lysines) (DGL) constitute promising nanomaterials applicable as a nonviral gene-delivery vector. In this study, we evaluate the transfection abilities of four DGL generations with special emphasis on the systematic description of the relationship of how generation (i.e., molecule size) affects the transfection efficacy. Using Hep2 cells, we demonstrated that the capability of unmodified DGL to deliver plasmid is of a magnitude lower than that of jetPEI. On the other hand, employing the Hep2 cell line stably transduced with eGFP, we observed that DGL G5 delivers the siRNA oligonucleotide with the same efficiency as Lipofectamine 2000. In further experiments, it was shown that DGL affords excellent ability to bind DNA, protect it against DNase I attack, and internalize it into cells.

• MeSH
• buněčné linie MeSH
• deoxyribonukleasa I metabolismus   MeSH
• lidé MeSH
• lipidy MeSH
• malá interferující RNA MeSH
• molekulární sekvence - údaje MeSH
• oligonukleotidy metabolismus   farmakokinetika   MeSH
• plazmidy farmakokinetika   MeSH
• polylysin chemie   farmakokinetika   MeSH
• sekvence nukleotidů MeSH
• transfekce metody   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zelené fluorescenční proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH