With the increased demand for beef in emerging markets, the development of quality-control diagnostics that are fast, cheap and easy to handle is essential. Especially where beef must be free from pork residues, due to religious, cultural or allergic reasons, the availability of such diagnostic tools is crucial. In this work, we report a label-free impedimetric genosensor for the sensitive detection of pork residues in meat, by leveraging the biosensing capabilities of graphene acid - a densely and selectively functionalized graphene derivative. A single stranded DNA probe, specific for the pork mitochondrial genome, was immobilized onto carbon screen-printed electrodes modified with graphene acid. It was demonstrated that graphene acid improved the charge transport properties of the electrode, following a simple and rapid electrode modification and detection protocol. Using non-faradaic electrochemical impedance spectroscopy, which does not require any electrochemical indicators or redox pairs, the detection of pork residues in beef was achieved in less than 45 min (including sample preparation), with a limit of detection of 9% w/w pork content in beef samples. Importantly, the sample did not need to be purified or amplified, and the biosensor retained its performance properties unchanged for at least 4 weeks. This set of features places the present pork DNA sensor among the most attractive for further development and commercialization. Furthermore, it paves the way for the development of sensitive and selective point-of-need sensing devices for label-free, fast, simple and reliable monitoring of meat purity.
Magnetic iron oxide nanocrystals (MIONs) are established as potent theranostic nanoplatforms due to their biocompatibility and the multifunctionality of their spin-active atomic framework. Recent insights have also unveiled their attractive near-infrared photothermal properties, which are, however, limited by their low near-infrared absorbance, resulting in noncompetitive photothermal conversion efficiencies (PCEs). Herein, we report on the dramatically improved photothermal conversion of condensed clustered MIONs, reaching an ultrahigh PCE of 71% at 808 nm, surpassing the so-far MION-based photothermal agents and even benchmark near-infrared photothermal nanomaterials. Moreover, their surface passivation is achieved through a simple self-assembly process, securing high colloidal stability and structural integrity in complex biological media. The bifunctional polymeric canopy simultaneously provided binding sites for anchoring additional cargo, such as a strong near-infrared-absorbing and fluorescent dye, enabling in vivo optical and photoacoustic imaging in deep tissues, while the iron oxide core ensures detection by magnetic resonance imaging. In vitro studies also highlighted a synergy-amplified photothermal effect that significantly reduces the viability of A549 cancer cells upon 808 nm laser irradiation. Integration of such-previously elusive-photophysical properties with simple and cost-effective nanoengineering through self-assembly represents a significant step toward sophisticated nanotheranostics, with great potential in the field of nanomedicine.
- MeSH
- buňky A549 MeSH
- fotochemické procesy MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- magnetické nanočástice chemie toxicita MeSH
- multimodální zobrazování metody MeSH
- myši MeSH
- optoakustické techniky metody MeSH
- teranostická nanomedicína metody MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The ability of bacteria to develop resistance to antibiotics is threatening one of the pillars of modern medicine. It was recently understood that bacteria can develop resistance even to silver nanoparticles by starting to produce flagellin, a protein which induces their aggregation and deactivation. This study shows that silver covalently bound to cyanographene (GCN/Ag) kills silver-nanoparticle-resistant bacteria at concentrations 30 times lower than silver nanoparticles, a challenge which has been so far unmet. Tested also against multidrug resistant strains, the antibacterial activity of GCN/Ag is systematically found as potent as that of free ionic silver or 10 nm colloidal silver nanoparticles. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, as theory and experiments confirm, there is marginal silver ion leaching, even after six months of storage, and thus very high cytocompatibility to human cells. Molecular dynamics simulations suggest strong interaction of GCN/Ag with the bacterial membrane, and as corroborated by experiments, the antibacterial activity does not rely on the release of silver nanoparticles or ions. Endowed with these properties, GCN/Ag shows that rigid supports selectively and densely functionalized with potent silver-binding ligands, such as cyanographene, may open new avenues against microbial resistance.
Controlled pulmonary drug delivery systems employing non-spherical particles as drug carriers attract considerable attention nowadays. Such anisotropic morphologies may travel deeper into the lung airways, thus enabling the efficient accumulation of therapeutic compounds at the point of interest and subsequently their sustained release. This study focuses on the fabrication of electrospun superparamagnetic polymer-based biodegradable microrods consisting of poly(l-lactide) (PLLA), polyethylene oxide (PEO) and oleic acid-coated magnetite nanoparticles (OA·Fe3O4). The production of magnetite-free (0% wt. OA·Fe3O4) and magnetite-loaded (50% and 70% wt. Fe3O4) microrods was realized upon subjecting the as-prepared electrospun fibers to UV irradiation, followed by sonication. Moreover, drug-loaded microrods were fabricated incorporating methyl 4-hydroxybenzoate (MHB) as a model pharmaceutical compound and the drug release profile from both, the drug-loaded membranes and the corresponding microrods was investigated in aqueous media. In addition, the magnetic properties of the produced materials were exploited for remote induction of hyperthermia under AC magnetic field, while the possibility to reduce transport losses and enhance the targeted delivery to lower airways by manipulation of the airborne microrods by DC magnetic field was also demonstrated.
AIM: To synthesize magnetic nanoparticles loaded with the SGLT2-inhibitor canagliflozin (CANA) and evaluate its anticancer potential under normoxic and hypoxic conditions in combination or not with radiotherapy. MATERIAL & METHODS: Iron oxide nanoparticles were synthesized via an alkaline hydrolytic precipitation of iron precursor in the presence of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate). CANA was conjugated to the nanoparticles using N-ethyl-N'-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide chemistry. The anticancer efficacy of the nanoparticles was evaluated in cancer cell lines and in a mouse PDV C57 tumor model. RESULTS: In the mouse xenograft cancer model, the combination of CANA-loaded nanoparticles with radiotherapy (in the presence of an external magnetic field at the tumor site) exhibited higher antitumor activity compared with the combination of free CANA with radiotherapy. CONCLUSION: The results obtained indicate the potential that the combination of selective delivery of a SGLT2 inhibitor such as CANA with radiotherapy holds as an anticancer treatment.
- MeSH
- canagliflozin chemie farmakologie MeSH
- glifloziny chemie farmakologie MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- magnetické nanočástice aplikace a dávkování chemie MeSH
- myši MeSH
- nádorová hypoxie účinky léků MeSH
- nádory farmakoterapie genetika radioterapie MeSH
- transportér 2 pro sodík a glukózu účinky léků MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- železité sloučeniny chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors.
- MeSH
- benzhydrylové sloučeniny aplikace a dávkování chemie MeSH
- buňky A549 MeSH
- glukosidy aplikace a dávkování chemie MeSH
- lidé MeSH
- magnetické nanočástice aplikace a dávkování chemie MeSH
- nádorová hypoxie účinky léků fyziologie MeSH
- nádorové buněčné linie MeSH
- nanomedicína metody MeSH
- nosiče léků aplikace a dávkování chemie MeSH
- systémy cílené aplikace léků metody MeSH
- transportér 2 pro sodík a glukózu antagonisté a inhibitory MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The increasing use of neonicotinoids in systematic seed treatment to crops is a serious cause of pollution of water resources and environment. Consequently, food sources can get eventually contaminated. To this end, it is desirable to develop suitable and effective platforms in order to obtain low-cost and sensitive sensors for neonicotinoids detection. In this work, graphene oxide modified electrodes were used as highly efficient electrochemical sensors for detection of two common insecticides - thiamethoxam and imidacloprid. The proposed sensor responded linearly in the concentration range of 10-200µmolL(-1) for both analytes and the detection limits were determined as low as 8.3µmolL(-1) and 7.9µmolL(-1) for thiamethoxam and imidacloprid, respectively. Analytical performance was also evaluated on spiked water and honey samples.
- MeSH
- analýza potravin ekonomika metody MeSH
- biosenzitivní techniky ekonomika metody MeSH
- chemické látky znečišťující vodu analýza MeSH
- dusíkaté sloučeniny analýza MeSH
- elektrochemické techniky ekonomika metody MeSH
- elektrody MeSH
- grafit chemie MeSH
- imidazoly analýza MeSH
- insekticidy analýza MeSH
- kontaminace potravin analýza MeSH
- limita detekce MeSH
- med analýza MeSH
- monitorování životního prostředí ekonomika metody MeSH
- oxaziny analýza MeSH
- oxidy chemie MeSH
- řeky chemie MeSH
- thiazoly analýza MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
The development of anticancer drug delivery systems which retain or enhance the cytotoxic properties of the drug to tumorous tissues, while reducing toxicity to other organs is of key importance. We investigated different poly(methacrylic acid)-g-poly(ethyleneglycol methacrylate) polymers as in situ coating agents for magnetite nanocrystallites. The obtained magnetic nano-assemblies were in turn thoroughly characterized for their structural, colloidal and physicochemical properties (drug loading capacity/release, magnetic field triggered drug release, cell uptake and localization) in order to select the best performing system. With the focus on in vivo validation of such magnetic drug delivery systems for first time, we selected cisplatin as the drug, since it is a potent anticancer agent which exhibits serious side effects due to lack of selectivity. In addition, cisplatin would offer facile determination of the metal content in the animal tissues for biodistribution studies. Alongside post-mortem Pt determination in the tissues, the biodistribution of the drug nanocarriers was also monitored in real time with PET-CT (positron emission tomography/computed tomography) with and without the presence of magnetic field gradients; using a novel chelator-free method, the nanoparticles were radiolabeled with 68Ga without having to alter their structure with chemical modifications for conjugation of radiochelators. The ability to be radiolabeled in such a straightforward but very robust way, along with their measured high MRI response, renders them attractive for dual imaging, which is an important functionality for translational investigations. Their anticancer properties were evaluated in vitro and in vivo, in a cisplatin resistant HT-29 human colon adenocarcinoma model, with and without the presence of magnetic field gradients. Enhanced anticancer efficacy and reduced toxicity was recorded for the cisplatin-loaded nanocarriers in comparison to the free cisplatin, particularly when a magnetic field gradient was applied at the tumor site. Post mortem and real-time tissue distribution studies did not reveal increased cisplatin concentration in the tumor site, suggesting that the enhanced anticancer efficacy of the cisplatin-loaded nanocarriers is driven by mechanisms other than increased cisplatin accumulation in the tumors.
- MeSH
- adenokarcinom farmakoterapie patologie MeSH
- antitumorózní látky aplikace a dávkování farmakokinetika farmakologie MeSH
- buňky HT-29 MeSH
- chemorezistence MeSH
- cisplatina aplikace a dávkování farmakokinetika farmakologie MeSH
- kyseliny polymethakrylové chemie MeSH
- lidé MeSH
- magnetické nanočástice * MeSH
- methakryláty chemie MeSH
- myši nahé MeSH
- myši SCID MeSH
- nádory tračníku farmakoterapie patologie MeSH
- PET/CT MeSH
- polyethylenglykoly chemie MeSH
- systémy cílené aplikace léků * MeSH
- tkáňová distribuce MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
- ligandy MeSH
- magnetické nanočástice chemie MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- poréznost MeSH
- povrchové vlastnosti MeSH
- systémy cílené aplikace léků * MeSH
- uvolňování léčiv * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Colloidal clusters of magnetic iron oxide nanocrystals (MIONs), particularly in the condensed pattern (co-CNCs), have emerged as new superstructures to improve further the performance of MIONs in applications pertaining to magnetic manipulation (drug delivery) and magnetic resonance imaging (MRI). Exploitation of the advantages they represent and their establishment in the area of nanomedicine demands a particular set of assets. The present work describes the development and evaluation of MION-based co-CNCs featuring for the first time such assets: High magnetization, as well as magnetic content and moment, high relaxivities (r2 = 400 and r2* = 905 s(-1) mMFe(-1)) and intrinsic loss power (2.3 nH m(2) kgFe(-1)) are combined with unprecedented colloidal stability and structural integrity, stealth and drug-loading properties. The reported nanoconstructs are endowed with additional important features such as cost-effective synthesis and storage, prolonged self-life and biocompatibility. It is finally showcased with in vivo multispectral optoacoustic tomography how these properties culminate in a system suitable for targeting breast cancer and for forceful in vivo manipulation with low magnetic field gradients.
- MeSH
- antibiotika antitumorózní aplikace a dávkování MeSH
- doxorubicin aplikace a dávkování MeSH
- magnety chemie MeSH
- myši nahé MeSH
- myši MeSH
- nádory prsu patologie MeSH
- nanočástice analýza chemie MeSH
- optoakustické techniky metody MeSH
- počítačová rentgenová tomografie metody MeSH
- polyethylenglykoly chemie farmakokinetika MeSH
- prsy patologie MeSH
- systémy cílené aplikace léků MeSH
- železité sloučeniny chemie farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
