Magnetic nanoparticles (MNPs) are being of great interest due to their unique purposes. Especially in medicine, application of MNPs is much promising. MNPs have been actively investigated as the next generation of targeted drug delivery for more than thirty years. The importance of targeted drug delivery and targeted drug therapy is to transport a drug directly to the centre of the disease under various conditions and thereby treat it deliberately, with no effects on the body. Usage of MNPs depends largely on the preparation processes to select optimal conditions and election agents to modify their surface. This review summarizes the most commonly used functionalization methods of the MNPs preparation methods and their use in targeted drug delivery and targeted therapy.

• MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• magnetismus MeSH
• nanočástice chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

In recent years, Fe oxide nanoparticles have been increasingly used in a wide range of biomedical applications, including magnetic resonance imaging, magnetic hyperthermia, targeted drug and gene delivery, cell tracking and magnetic cell separation. Although the number of studies examining the toxicity of Fe oxide nanoparticles is growing exponentially, the in-depth toxicity studies are scanty and the mechanisms underlying their cytotoxicity remain still mostly unclear. This review focuses on the assessment of the in vitro and in vivo toxicity of Fe oxide nanoparticles and discusses the biological processes underlying their toxicity including cellular uptake, production of reactive O species, modulation of actin and microtubular cytoskeleton, DNA damage and activation of intracellular signalling pathways. The significance of the proteins associated with Fe oxide nanoparticles and assays for assessing their cytotoxicity are also considered. We have tested cytotoxic effects of silica-coated Fe oxide nanoparticles on human lung adenocarcinoma, epithelial cell line A549 using the xCELLigence system for label-free and real-time monitoring of cell viability.

• Klíčová slova
• MNPs, SPIONs,
• MeSH
• kovové nanočástice chemie   škodlivé účinky   terapeutické užití   toxicita   MeSH
• lidé MeSH
• magnetické nanočástice * chemie   škodlivé účinky   terapeutické užití   toxicita   MeSH
• oxidační stres MeSH
• techniky in vitro MeSH
• testy toxicity * MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell are designed and synthesized. The architecture of particles is analyzed and confirmed in detail using electron tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor are demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser.

• MeSH
• ablace metody   MeSH
• biokompatibilní materiály farmakokinetika   MeSH
• cílená molekulární terapie metody   MeSH
• HeLa buňky účinky léků   MeSH
• indukovaná hypertermie metody   MeSH
• karbocyaniny chemie   MeSH
• laserová terapie metody   MeSH
• lidé MeSH
• nanočástice chemie   MeSH
• nanodiamanty chemie   MeSH
• nanoslupky chemie   MeSH
• polyethylenglykoly chemie   MeSH
• receptory transferinu metabolismus   MeSH
• transferin chemie   farmakologie   MeSH
• zlato chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Nanoparticles as drug delivery vehicles pose an exciting and promising future for cancer treatment, and offer particular benefits not only for cancer treatment, but also for overcoming of multidrug resistance in cancer tissues. Targeted delivery of anti-neoplastic drugs by nanoparticles promises enhanced drug efficacy, selectivity and reduced systemic toxicity. Nanoparticle systems have unique properties that allow for both passive and active targeting of tumors. Active targeting of nanoparticles, that usually involve surface proteins known to be upregulated in cancer cells, increases accumulation in a tumor. Targeting molecules include antibodies or their fragments, aptamers, or small molecules. This review describes a comprehensive overview of different targeting of nanodrugs.

• MeSH
• lidé MeSH
• nádory * farmakoterapie   MeSH
• nanočástice * MeSH
• nosiče léků * farmakologie   chemie   MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Two types of magnetic binary nanocomposites, Ag@Fe(3)O(4) and γ-Fe(2)O(3)@Ag, were synthesized and characterized and their antibacterial activities were tested. As a magnetic component, Fe(3)O(4) (magnetite) nanoparticles with an average size of about 70 nm and monodisperse γ-Fe(2)O(3) (maghemite) nanoparticles with an average size of 5 nm were used. Nanocomposites were prepared via in situ chemical reduction of silver ions by maltose in the presence of particular magnetic phase and molecules of polyacrylate serving as a spacer among iron oxide and silver nanoparticles. In the case of the Ag@Fe(3)O(4) nanocomposite, silver nanoparticles, caught at the surfaces of Fe(3)O(4) nanocrystals, were around 5 nm in a size. On the contrary, in the case of the γ-Fe(2)O(3)@Ag nanocomposite, ultrafine γ-Fe(2)O(3) nanoparticles surrounded silver nanoparticles ranging in a size between 20 and 40 nm. In addition, the molecules of polyacrylate in this nanocomposite type suppress considerably interparticle magnetic interactions as proved by magnetization measurements. Both synthesized nanocomposites exhibited very significant antibacterial and antifungal activities against ten tested bacterial strains (minimum inhibition concentrations (MIC) from 15.6 mg/L to 125 mg/L) and four candida species (MIC from 1.9 mg/L to 31.3 mg/L). Moreover, acute nanocomposite cytotoxicity against mice embryonal fibroblasts was observed at concentrations of higher than 430 mg/L (Ag@Fe(3)O(4)) and 292 mg/L (γ-Fe(2)O(3)@Ag). With respect to the non-cytotoxic nature of the polyacrylate linker, both kinds of silver nanocomposites are well applicable for a targeted magnetic delivery of silver nanoparticles in medicinal and disinfection applications.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• antifungální látky chemie   farmakologie   MeSH
• Bacteria účinky léků   MeSH
• houby účinky léků   MeSH
• kovové nanočástice chemie   MeSH
• magnetismus MeSH
• mikrobiální testy citlivosti MeSH
• myši MeSH
• nanokompozity chemie   MeSH
• spektroskopie Mossbauerova MeSH
• stříbro chemie   farmakologie   MeSH
• testování materiálů MeSH
• velikost částic MeSH
• železité sloučeniny chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Východiska: Ferritin je globulární vnitrobuněčný protein, který slouží jako hlavní zásobárna železa. U nádorových onemocnění je plazmatická koncentrace ferritinu zvýšená. V řadě studií bylo zjištěno, že nádorové buňky exprimují ve zvýšené míře transferinové receptory (TfR). Zvýšená exprese TfR byla pozorována i u karcinomu prostaty. Apoferritin (APO) lze využít jako proteinový nanotransportér, do kterého je možné enkapsulovat vhodnou léčivou látku. Bylo zjištěno, že nanočástice zvyšují prostupnost nanotransportérů do nádorové buňky a vykazují fototermální efekt. Cílem projektu bylo enkapsulovat doxorubicin (DOX) do APO a vytvořený APO/DOX modifikovat zlatými (gold nanoparticles - AuNPs) a stříbrnými (silver nanoparticles prepared by green synthesis - AgNPsGS) nanočásticemi. Metody: Pro charakterizaci APO byla použita 10% gelová elektroforéza (sodium dodecylsulphate polyacrylamide gel electrophoresis - SDS-PAGE) - 120 V, 60 min, 24 mM Tris, 0,2 M glycin, 3 mM SDS. Fluorescence DOX (Ex 480 nm, Em 650 nm) s typickým absorpčním maximem v 560 nm. Elektrochemické měření bylo provedeno v Brdičkově roztoku (tříelektrodové zapojení). AgNPsGS byly připraveny zelenou syntézou z jetele lučního (Trifolium pratense L.). Výsledky: Byla provedena elektroforetická studie APO a APO/DOX (5- 100 μg//ml). Bylo sledováno chování APO a APO/DOX (10 μM) v závislosti na pH. APO v kyselém prostředí tvoří subjednotky o velikosti asi 20 kDa a v neutrálním a zásaditém prostředí se zformuje na globulární protein o velikosti asi 450 kDa. U APO/DOX byla pozorována změna mobility (asi o 10 %). Na povrchu APO/DOX byl vytvořen film z AuNPs. APO/DOX/AuNPs byl následně promyt ultračistou vodou. Bylo sledováno uvolnění DOX v závislosti na pH. Množství analyzovaného DOX se zvýšilo až o 50 %. Dále byl navržen a připraven komplex AgNPsGS-DOX (1 mg AgNPsGS/100 μM DOX). Takto připravený komplex AgNPsGS-DOX byl uzavřen do APO. Pro další zlepšení terapeutické účinnosti byl připravený komplex APO/AgNPsGS-DOX pokryt vrstvou AuNPs. Vytvořený APO/AgNPsGS-DOX/AuNPs prokázal svoji stabilitu a při změně fyzikálních parametrů byl z komplexu uvolněn DOX. Závěr: Byly připraveny a modifikovány nanokomplexy APO pro zvýšení terapeutické účinnosti protinádorové léčby. Zacílení k nádorové buňce bylo na TfR nebo efektem zvýšené propustnosti a retence. Uvolnění léčiva bylo možné změnou pH nebo fototermální aktivací, která bude nyní testována.

Background: Ferritin is a globular intracellular protein that acts as the main reservoir for iron. Malignancies are associated with increased plasma ferritin concentrations. A number of studies show that tumor cells express high levels of transferrin receptors (TfR). Increased TfR expression was observed in prostate carcinoma. Apoferritin (APO) can be used as a protein nanotransporter into which a suitable medicinal substance can be encapsulated. Nanoparticles increase the permeability of tumor cells to nanotransporters and have a photothermal effect. The aim of this study was to encapsulate doxorubicin (DOX) into APO and to modify the resulting APO/DOX with gold (AuNPs) and silver nanoparticles prepared by green synthesis (AgNPsGS). Methods: APO was characterized using 10% sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS- -PAGE) – 120 V, 60 min, 24 mM Tris, 0.2 M glycine, 3 mM SDS. DOX fluorescence (Ex 480 nm; Em 650 nm) was observed, with a typical absorption maximum at 560 nm. Electrochemical measurement was performed in Brdicka solution (three-electrode setup). AgNPsGS were prepared by green synthesis using clover (Trifolium pratense L.). Results: An electrophoretic study of APO and APO/DOX (5–100 μg/mL) was performed and the behavior of APO and APO/DOX (10 μM) as a function of pH was monitored. In an acidic environment, APO forms subunits of about 20 kDa; in an alkaline medium, it forms a globular protein of about 450 kDa. A change in APO/DOX mobility (about by 10%) was observed. A fi lm of gold nanoparticles was applied to the APO/DOX surface. APO/DOX-AuNPs were washed with ultra-pure water. pH-dependent release of DOX a was monitored. The amount of DOX analyzed was increased by up to 50%. Furthermore, an AgNPsGS-DOX complex (1 mg AgNPsGS/100 μM DOX) was generated and prepared. Subsequently, the AgNPsGS-DOX complex was encapsulated into APO. To further improve therapeutic efficacy, the APO/AgNPsGS-DOX complex was coated with an Au layer. APO/AgNPsGS-DOX/AuNPs were stable and DOX was released from the complex after physical parameters had changed. Conclusion: APO nanocomplexes were prepared and modified to increase therapeutic efficacy against tumors. Tumor cell targeting was achieved by binding to TfR and via increased tumor cell permeability and retention. Release of the drug was made possible due to a pH change and photothermal activation that will now be tested.

• Klíčová slova
• nanotransportér, poferritinový nanotransportér, transferinové receptory, stříbrné nanočástice, zlaté nanočástice,
• MeSH
• apoferritiny farmakologie   MeSH
• kovové nanočástice MeSH
• lékové transportní systémy * metody   MeSH
• lidé MeSH
• nádory prostaty * farmakoterapie   MeSH
• nanomedicína * metody   MeSH
• objevování léků MeSH
• stříbro MeSH
• zlato MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH

Odstranění mikrobiálního biofilmu a potlačení jeho tvorby jsou v současné době velkou výzvou, která vyžaduje citlivější a účinnější strategie s ohledem k nárůstu mikrobiálních rezistencí. Nanočástice zaměřené na eradikaci biofilmu vyvolávají v posledních deseti letech zájem kvůli svým vlastnostem. Tyto nanočástice mají široké spektrum biologických účinků a mezi nimiž je významná antibiofilmová aktivita. Daří se jim proniknout do biofilmové matrice, která působí jako bariéra pro mnoho antibiotik a dezinfekčních prostředků.

Eradication of microbial biofilm and prevention of its formation is currently a major challenge that requires more sensitive and effective strategies due to increasing resistence of microorganisms. Nanoparticles targeted on biofilm eradication have gained enormous popularity over the last ten years due to their unique properties. These nanoparticles have a wide range of biological applications, including a significant antibiofilm activity. They are able to penetrate into a biofilm matrix that serves as a barrier against many antibiotics and disinfectants.

• MeSH
• antiinfekční látky farmakologie   izolace a purifikace   MeSH
• biofilmy účinky léků   MeSH
• hořčík MeSH
• matrix extracelulárních polymerních látek mikrobiologie   účinky léků   MeSH
• nanočástice * chemie   terapeutické užití   MeSH
• oxid zinečnatý MeSH
• stříbro MeSH
• železo MeSH
• zlato MeSH
• Publikační typ
• práce podpořená grantem MeSH

Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage. Comprehensive characterization of the mutants revealed that only the variant carrying four tryptophan substitutions per subunit retained the ability to disassemble and reassemble properly. As a proof of concept, we evaluated the loading capacity of this mutant with ellipticine, a natural hydrophobic indole alkaloid with multimodal anticancer activity. Our data demonstrated that this specific mutant exhibited significantly higher efficiency in loading ellipticine compared to human H ferritin. Furthermore, to evaluate the versatility of this hydrophobicity-enhanced ferritin nanoparticle as a drug carrier, we conducted a comparative study by also encapsulating doxorubicin, a commonly used anticancer drug. Subsequently, we tested both ellipticine and doxorubicin-loaded nanoparticles on a promyelocytic leukemia cell line, demonstrating efficient uptake by these cells and resulting in the expected cytotoxic effect.

• MeSH
• apoferritiny genetika   MeSH
• doxorubicin farmakologie   chemie   MeSH
• elipticiny * MeSH
• ferritiny genetika   chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• tryptofan MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

• MeSH
• koncentrace vodíkových iontů MeSH
• lékové transportní systémy * MeSH
• ligandy MeSH
• magnetické nanočástice chemie   MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• poréznost MeSH
• povrchové vlastnosti MeSH
• uvolňování léčiv * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Routine cancer treatment often causes damage to whole human organism, because cytostatic drugs, which are used during the treatment and whose function is to stop growth of cancer cells, affect also healthy cells and untargeted tissues. Due to this fact, nanocarriers and targeted drug delivery have been recently studied. Side effects and organ damage can be reduced by using nanocarriers and targeted drug delivery. The aim of this assay was to monitor and characterize apoferritin as a nanocarrier for targeted drug delivery. In this work the surface of nanocarrier composed of apoferritin with encapsulated doxorubicin was modified with gold nanoparticles or chloroauric acid, conjugated with linker (HWR peptide) because of correct binding of the antibody and labeled with specific antibody. In this assay the resulting nanocarrier was studied with gel electrophoresis and fluorescent methods.

• Klíčová slova
• nanotransportér, teranostika,
• MeSH
• apoferritiny * MeSH
• doxorubicin MeSH
• elektroforéza MeSH
• ELISA MeSH
• fluorescenční protilátková technika MeSH
• imunoglobulin G MeSH
• kovové nanočástice * MeSH
• lékové transportní systémy * MeSH
• nanomedicína MeSH
• protilátky MeSH
• zlato MeSH
• Publikační typ
• práce podpořená grantem MeSH