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1.
J Nanobiotechnology ; 18(1): 14, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941495

RESUMO

BACKGROUND: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. RESULTS: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. CONCLUSION: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.


Assuntos
Portadores de Fármacos/química , Compostos Férricos/química , Nanopartículas de Magnetita/química , Próteses e Implantes , Dióxido de Silício/química , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Feminino , Corantes Fluorescentes/química , Membro Posterior , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos BALB C , Ortopedia , Polietilenoglicóis/química , Porosidade , Rodaminas/química , Silanos/química , Distribuição Tecidual
2.
J Photochem Photobiol B ; 202: 111716, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821944

RESUMO

Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency anesthetic drug delivery system. Chitosan is a unique class of biomaterials that is widely used in medical devices. The surface engineering of ZnFe2O4 nanoparticles was performed by coating with chitosan using simple precipitation method. Then, multi-active anesthetic drug (Lidocaine) was loaded into nano-ferrite to form a drug delivery vehicle. The prepared drug-vesicle was characterized by using XRD, FTIR, SEM, XPS and TGA analysis. XRD analysis proved the face center cubic structure of zinc nanoferrite. The sustained delivery of Lidocaine (LDC) from CS coated nanoferrite (CS/ZnFe2O4) was stimulated by pH and temperature responsive characteristics of vesicles. The in vitro cytotoxicity of the CS/ZnFe2O4 particles towards fibroblast cells was analyzed by using MTT assay. The drug loaded CS/ZnFe2O4 particles exhibit high biocompatibility and sustained drug release in the physiological pH environment (4.8, 5.5 and 7.4) and temperature responsive (25 and 37 °C) of normal tissues and also drug loading efficiency was measured.


Assuntos
Anestésicos/química , Quitosana/química , Portadores de Fármacos/química , Nanoestruturas/química , Anestésicos/metabolismo , Anestésicos/uso terapêutico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Lidocaína/química , Lidocaína/metabolismo , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Nanoestruturas/toxicidade , Dor/tratamento farmacológico , Ratos , Temperatura Ambiente
3.
Chemosphere ; 238: 124562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442774

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) have been widely studied for different biomedical and environmental applications. In this study we evaluated the toxicity and potential alterations of relevant physiological parameters caused to the microalga Chlamydomonas reinhardtii (C. reinhardtii) upon exposure to SPION. The results showed dose-dependent toxicity. A mechanistic study combining flow cytometry and physiological endpoints showed a toxic response consisting of a decrease in metabolic activity, increased oxidative stress and alterations in the mitochondrial membrane potential. Additionally, and due to the light absorption of SPION suspensions, we observed a significant shading effect, causing a marked decrease in photosynthetic activity. In this work, we demonstrated for the first time, the internalization of SPION by endocytosis in C. reinhardtii. These results demonstrated that SPION pose a potential risk for the environment if not managed properly.


Assuntos
Chlamydomonas reinhardtii/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
4.
Int J Nanomedicine ; 14: 8421-8432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749616

RESUMO

Purpose: Immune activation with T cell tumor infiltration is beneficial for the prognosis of patients suffering from solid cancer. Depending on their immune status, solid tumors can be immunologically classified into three groups: "hot" tumors are infiltrated with T lymphocytes, "cold" tumors are not infiltrated and "immune excluded" tumors are only infiltrated in the peripheral tumor tissue. Checkpoint inhibitors provide new therapeutic options for "hot" tumors by triggering the immune response of T cells. In order to enable this for cold tumors as well, T cells must be enriched in the tumor. Therefore, we use the principle of magnetic targeting to guide T cells loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate) to the tumor by an externally applied magnetic field. Methods: SPIONCitrate were produced by alkaline coprecipitation of iron(II) and iron(III) chloride and in situ coating with sodium citrate. The concentration-dependent cytocompatibility of the particles was determined by flow cytometry and blood stability assays. Atomic emission spectroscopy was used for the quantification of the particle uptake into T lymphocytes. The attractability of the loaded cells was observed by live-cell imaging in the presence of an externally applied magnetic field. Results: SPIONCitrate displayed good cytocompatibility to T cells and did not show any sign of aggregation in blood. Finally, SPIONCitrate-loaded T cells were strongly attracted by a small external magnet. Conclusion: T cells can be "magnetized" by incorporation of SPIONCitrate for magnetic targeting. The production of the particle-cell hybrid system is straightforward, as the loading process only requires basic laboratory devices and the loading efficiency is sufficient for cells being magnetically controllable. For these reasons, SPIONCitrate are potential suitable candidates for magnetic T cell targeting.


Assuntos
Ácido Cítrico/química , Dextranos/química , Imunoterapia , Magnetismo , Nanopartículas de Magnetita/química , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Dextranos/sangue , Dextranos/toxicidade , Dextranos/ultraestrutura , Humanos , Ferro/metabolismo , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Neoplasias/sangue , Espécies Reativas de Oxigênio/metabolismo
5.
J Photochem Photobiol B ; 201: 111648, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710924

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have been recently recognized as highly efficient photothermal therapy (PTT) agents. Here, we demonstrate, for the first time to our knowledge, dose and laser intensity dependent PTT potential of small, spherical, 3-aminopropyltrimethoxysilane coated cationic superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) in aqueous solutions upon irradiation at 795 nm. Indocyanine green (ICG) which has been recently used for photodynamic therapy (PDT), was loaded to APTMS@SPIONs to improve the stability of ICG and to achieve an effective mild PTT and PDT (dual therapy) combination for synergistic therapeutic effect on cancer cells via a single laser treatment in the near infrared (NIR). Neither APTMS@SPIONs nor ICG-APTMS@SPIONs showed dark toxicity on MCF7 breast and HT29 colon cancer cell lines. A safe laser procedure was determined as 10 min irradiation at 795 nm with 1.8 W/cm2 of laser intensity, at which APTMS@SPION did not cause a significant cell death. However, free ICG reduced cell viability at and above 10 µg/ml under these conditions along with generation of reactive oxygen species (ROS), more effectively in MCF7. ICG-APTMS@SPION treated cells showed 2-fold increase in ROS generation and near complete cell death at and below 5 µg/ml ICG dose, even in less sensitive HT29 cells after a single laser treatment at NIR, which would be safe for the healthy tissue and provide a longer penetration depth. Besides, both components can be utilized for diagnosis and the overall composition may be used for optical-image guided phototherapy in the NIR region.


Assuntos
Verde de Indocianina/química , Nanopartículas de Magnetita/toxicidade , Propilaminas/química , Silanos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia , Fotoquimioterapia , Fototerapia , Espécies Reativas de Oxigênio/metabolismo , Temperatura Ambiente
6.
Ecotoxicol Environ Saf ; 186: 109743, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31593827

RESUMO

Nanoparticles (NPs) production is increasing worldwide. These products are likely to end up in aquatic environments. However, few studies evaluated the chronic toxicity of iron-based NPs (Fe-NPs) to cladocerans and their potential ecotoxicological hazards. In this study we aimed to investigate the effects of iron oxide nanoparticles (Fe3O4-NPs) to Ceriodaphnia silvestrii Daday, 1902, assessing acute (48 h) and chronic toxicity (up to 14 d). Besides traditional endpoints (immobility and lethality), we also evaluated physiological responses (respiration rates) in a 48 h-exposure. No immobility was observed (EC50 > 100 mg L-1) after 48 h, whereas respiration rates at the highest concentration were 400% of that in control, indicating that this endpoint was more sensitive during acute toxicity. In chronic assays, Fe3O4-NPs affected body length (8.24% growth inhibition in 7 d-exposure) and number of eggs (7-d IC10: 3.53, IC20: 6.69 mg Fe L-1) and neonates (7-d IC10: 1.25, IC20: 3.75 mg Fe L-1). Based on species sensitivity distribution (SSD), C. silvestrii was a sensitive organism, suggesting Fe-NPs as a possible threat for this species. Our results also indicate that the NPs caused a physical barrier, impairing food absorption, since we observed NPs agglomerations into cladocerans' gut. We demonstrate that Fe3O4-NPs affects C. silvestrii metabolism and reproduction and our results support the use of sublethal endpoints to assess environmental safety. The release of these NPs into freshwater environments should be carefully evaluated, since disturbances on cladoceran population dynamics could cause strong impacts on the entire food web structure and ultimately on ecosystem functioning.


Assuntos
Cladóceros/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cladóceros/fisiologia , Ecossistema , Reprodução/efeitos dos fármacos , Testes de Toxicidade
7.
Mater Sci Eng C Mater Biol Appl ; 104: 109810, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499939

RESUMO

The problems associated with hydrophobic anticancer drugs are among the most important challenges to achieve efficient therapeutics for cancer treatment. In this study, PEGylated curcumin was used as the surface modification of magnetic nanoparticles (MNP@PEG-Cur) in order to simultaneously take advantage of magnetic targeting characteristic of nanoparticles and PEG conjugated drug. Curcumin was conjugated through EDC/NHS chemistry to the PEG hydroxyl functional groups, and then physically decorated on the surface of magnetic nanoparticles (MNP). The analysis of the conjugate and nanoparticles by FT-IR, 1HNMR, FE-SEM, TEM, EDX, TGA and VSM confirmed the successful synthesis and proper physicochemical properties of MNP@PEG-Cur nanoparticles. The carrier showed pH dependent drug release profile with higher drug release at acidic media (pH = 5.4) compared to neural condition (pH = 7.4). In addition, LD50 and hemolysis assay confirmed the biocompatibility of MNP@PEG-Cur. The cell viability assay also revealed that neither carrier, nor curcumin-loaded nanoparticles are cytotoxic at physiologic pH (7.4).


Assuntos
Materiais Biocompatíveis/farmacologia , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita/toxicidade , Polietilenoglicóis/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Curcumina/síntese química , Curcumina/química , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Células MCF-7 , Campos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Polietilenoglicóis/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
8.
Int J Nanomedicine ; 14: 6103-6115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447555

RESUMO

Purpose: Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs. Methods and results: Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe3O4 nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis. Conclusions: NAC modifying could suppress the toxic effects of Fe3O4 nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Compostos Férricos/toxicidade , Nanopartículas de Magnetita/toxicidade , Miócitos Cardíacos/patologia , Oxigênio/farmacologia , Animais , Autofagia/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Nanopartículas de Magnetita/ultraestrutura , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Ratos , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/toxicidade
9.
Nanotechnology ; 30(42): 425102, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31261137

RESUMO

Multifunctional nanomedicines featuring high drug loading capacity, controllable drug release and real-time self-monitoring are attracting increasing attention due to their potential to improve cancer therapeutic efficacy. Herein, a new kind of Fe3O4@C-based nanoparticles modified with isoreticular metal organic frameworks (IRMOF-3), folic acid (FA) and detachable polyethylene glycol (PEG) under tumor microenvironment was developed. The core-shell structured Fe3O4@C was synthesized via the one-pot solvothermal reaction and the IRMOF-3 layers were coated on the outer shell of Fe3O4@C through layer-by-layer coating method. The FA and PEG were conjugated on the surface of nanoparticles by reacting with the amine groups provided by IRMOF-3. The as-synthesized nanoparticles showed stable photothermal effect, superparamagnetic properties and blue fluorescence characteristic under 360 nm irradiation. The in vitro experiments showed that the drug loaded nanoparticles exhibit pH-dependent drug release property, and PEGylation was proved effective in suppressing burst drug release (only 8.0% of drugs were released within 95 h). The confocal laser scanning microscopy study revealed that the as-synthesized nanoparticles could serve as a cell imaging agent and the cell internalization can be significantly enhanced after FA modified. The IRMOF-3 modified nanoparticles showed negligible cytotoxicity and the drug loaded nanoparticles showed pH/photothermal-stimuli enhanced cytotoxicity in vitro. It is believed that the present smart drug delivery platforms will hold great potential in imaging guided drug delivery and cancer therapy.


Assuntos
Antineoplásicos/química , Carbono/química , Portadores de Fármacos/química , Óxido Ferroso-Férrico/química , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Nanopartículas de Magnetita/toxicidade , Estruturas Metalorgânicas/química , Microscopia Confocal , Polietilenoglicóis/química
10.
Mater Sci Eng C Mater Biol Appl ; 102: 324-340, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31147005

RESUMO

Despite the fact that magnetic iron oxide nanoparticles (Fe3O4-MNPs) considered as the most promising nanoparticles (NPs) in biomedicine and environmental biotechnology, their safety and ecotoxicological impacts of biogenic and chemogenic routes of Fe3O4-MNPs in the marine aquatic system is scarcely studied. In this work, we report the optimized and suitable phyco-synthesis route for nano-Fe3O4 based on the six selected species of the Persian Gulf seaweeds: Ulva prolifera, U. flexuosa, U. linza, U. intestinalis, U. clathrata, and Sargassum boveanum. Moreover, antibacterial activities and acute zooplanktonic responses in Artemia salina and acorn barnacle Amphibalanus amphitrite to chemogenic and biogenic Fe3O4-MNPs, were evaluated. Although all the seaweeds extract showed reducing potential for Fe3O4-MNPs green synthesis - mainly on the basis of characterization results- the algal route selectivity has been demonstrated to be important for the biosynthesis of magnetite NPs. Herein, the cubo-spherical and polydisperse U. prolifera-derived Fe3O4-MNPs with particles sizes of 9.59 nm were the best ones. The comparative zooplanktonic cytotoxicity of chemo- and bio-route of Fe3O4-MNPs exhibited no acute toxicity in nauplii and adults of A. salina (96-h EC50 ≥ 1000 mg/L) and the potential of toxicity in A. amphitrite nauplii (48-h EC50 = 466.5 and 842.3 mg/L for chemo- and bio-route of Fe3O4-MNPs, respectively). The in vitro antimicrobial activity of both chemo- and bio-route of magnetite NPs to selective human pathogenic bacteria and fungi (i.e. n = 11) showed strong antagonistic activity against Staphylococcus epidermidis, Bacillus subtilis, B. pumulis, and Saccharomyces cerevisiae. In conclusion, these findings demonstrate the optimized phyco-fabrication of Fe3O4-MNPs as promising nontoxic approach in ecobiotechnology, the new insight about the potential adverse effects of chemosynthesized Fe3O4-MNPs to crustacean zoo-organisms after their possible entrance into the marine environments, and bio/chemo-route Fe3O4-MNPs as pivotal agent for nanoantimicrobials.


Assuntos
Antibacterianos/farmacologia , Nanopartículas de Magnetita/química , Ulva/química , Zooplâncton/efeitos dos fármacos , Adsorção , Animais , Artemia/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bioensaio , Fungos/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Magnetometria , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Alga Marinha/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Termogravimetria , Thoracica/efeitos dos fármacos , Testes de Toxicidade , Difração de Raios X
11.
Cell Biochem Biophys ; 77(3): 213-225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115834

RESUMO

Recently, due to their promising applications in biomedicine, magnetic iron oxide nanoparticles (MPs) have become one of the research hotspots in the nanomedicine field. Since various synthetic modifications have been widely applied to these nanoparticles for better targeting behaviors, it is meaningful to apply the optimal magnetic field condition for each case. This will enable creating a safe and efficient drug targeting using different types of MPs. In the present study, we aimed to find out any changes of transepithelial transport of polysaccharide-coated MPs by applying the continuous or the pulsatile magnetic field condition. Our results with heparin-functionalized MPs indicate that the particle concentrations and the external magnetic field could influence the transepithelial permeability of the particles. In the presence of a continuously applied magnetic density, heparin-MPs at high concentrations, by forming magnetically-induced aggregation of particles over the cell surface layer, showed a lower cellular transport than those at low concentrations. Furthermore, the results from the quantitative chemical assays and imaging analyses showed that transepithelial transport of heparin-MPs (negatively charged) under the pulsatile magnetic field was higher than that under the continuous magnetic field (CP), whereas the starch-MPs (neutrally charged) showed a small difference in transepithelial transport or cell retention between pulsatile vs. continuous magnetic field conditions. Taken together, our results suggest that the external magnetic field should be differentially applied to control the cellular drug transport depending on the physicochemical properties of the surface chemistry of magnetic particles.


Assuntos
Compostos Férricos/química , Nanopartículas de Magnetita/química , Polissacarídeos/química , Animais , Membrana Celular/química , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cães , Heparina/química , Células Madin Darby de Rim Canino , Campos Magnéticos , Nanopartículas de Magnetita/toxicidade , Microscopia Eletrônica de Transmissão , Propriedades de Superfície
12.
PLoS One ; 14(3): e0213852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30889203

RESUMO

Glioblastoma multiforme (GBM) is the most common type of malignant gliomas, characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fueled a search for new therapeutic targets and treatment modalities. Here we report new approach towards RNA interference therapy of glioblastoma multiforme based on the magnetic nanoparticles delivery of the double-stranded RNA (dsRNA) with homological sequences to mRNA of tenascin-C (TN-C), named ATN-RNA. The obtained nanocomposite consisted of polyethyleneimine (PEI) coated magnetic nanoparticles conjugated to the dsRNA show high efficiency in ATN-RNA delivery, resulting not only in significant TN-C expression level suppressesion, but also impairing the tumor cells migration. Moreover, synthesized nanomaterials show high contrast properties in magnetic resonance imaging (MRI) and low cytotoxicity combining with lack of induction of interferon response. We believe that the present work is a successful combination of effective, functional, non-immunostimulatory dsRNA delivery system based on magnetic nanoparticles with high potential for further application in GBM therapy.


Assuntos
Terapia Genética/métodos , Nanopartículas de Magnetita/química , RNA de Cadeia Dupla/química , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Polietilenoimina/química , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , RNA Mensageiro/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Tenascina/genética , Tenascina/metabolismo , Transfecção/métodos
13.
ACS Appl Mater Interfaces ; 11(12): 11194-11201, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30830737

RESUMO

The active and passive electrophysiological properties of blood and tissue have been utilized in a vast array of clinical techniques to noninvasively characterize anatomy and physiology and to diagnose a wide variety of pathologies. However, the accuracy and spatial resolution of such techniques are limited by several factors, including an ill-posed inverse problem, which determines biological parameters and signal sources from surface potentials. Here, we propose a method to noninvasively modulate tissue conductivity by aligning superparamagnetic iron oxide-loaded erythrocytes with an oscillating magnetic field. A prototype device is presented, which incorporates a three-dimensional set of Helmholtz coil pairs and fluid-channel-embedded electrode arrays. Alignment of loaded cells (∼11 mM iron) within a field of 12 mT is demonstrated, and this directed reorientation is shown to alter the conductivity of blood by ∼5 and ∼0.5% for stationary and flowing blood, respectively, within fields as weak as 6-12 mT. Focal modulation of conductivity could drastically improve numerous bioimpedance-based detection modalities.


Assuntos
Compostos Férricos/química , Nanopartículas de Magnetita/química , Células Cultivadas , Condutividade Elétrica , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Campos Magnéticos , Nanopartículas de Magnetita/toxicidade , Microscopia Eletrônica de Transmissão , Análise Serial de Tecidos
14.
Nanoscale ; 11(14): 6905-6915, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30912773

RESUMO

A main feature of biofilms is the self-produced extracellular polymeric substances (EPSs) that act as a protective shield, preventing biocide penetration. We use magnetic iron oxide nanoparticles (MNPs) in combination with magnetic fields to damage the biofilm matrix and cause detachment. A Methicillin-resistant Staphylococcus aureus (MRSA) biofilm strain is used to demonstrate the efficacy of the methodology with different sizes and concentrations of MNPs under AC and DC applied field conditions. We achieve up to a nearly 5 log10 reduction in biofilm bacteria after treatment with 30 mg mL-1 of 11 nm MNPs using a magnetic field. The MNPs cause significant mechanical disruption to the matrix and lead to biofilm dispersal. In addition, using magnetic hyperthermia further affects biofilm damage.


Assuntos
Biofilmes/efeitos dos fármacos , Compostos Férricos/química , Nanopartículas de Magnetita/toxicidade , Campos Magnéticos , Nanopartículas de Magnetita/química , Staphylococcus aureus Resistente à Meticilina/fisiologia , Tamanho da Partícula
15.
Amino Acids ; 51(6): 929-943, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915572

RESUMO

Stem cells have been widely exploited as remedial agents in regenerative medicine due to its tremendous potential in treatment of various debilitating diseases. In spite of this fact, there is need of a reliable, clinically applicable cell tracker for deciphering the homing and distribution of stem cells post-transplantation. Researchers have proposed the use of superparamagnetic magnetite (Fe3O4) nanoparticles for in vivo and in vitro tracking and imaging of stem cells. However, there is not much understanding of the chemical coatings on the nanoparticles, which is very important for the sustainability of stem cells in biological system. For any biomedical applications, the surface properties and the core structure of nanoparticles play a significant role. This study reports surface modification of magnetic Fe3O4 nanofluid with biocompatible amino acids viz., arginine and histidine to maintain colloidal stability at neutral pH, impart least disruption when encountered with the biological system and allow labeling with mesenchymal stem cells (MSCs). The size of amino acids-modified magnetic nanoferrofluid (AA@MNFs) was restricted to 15-25 nm for enhanced uptake in stem cells. In vitro cytotoxicity profile of stem cells labeled AA@MNFs was estimated using various assays like MTT, LDH and AO/EtBr followed by detailed pre-clinical toxicity assessment of AA@MNFs which illustrated least toxicity effects in major tissues of the animals. In vitro MRI scans of the stem cells labeled AA@MNFs confirmed the suitability of the reported ferrofluids for the use as MR contrast agents.


Assuntos
Meios de Contraste/química , Meios de Contraste/toxicidade , Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Arginina/química , Materiais Biocompatíveis/química , Linhagem Celular , Rastreamento de Células , Feminino , Histidina/química , Humanos , Nanopartículas de Magnetita/toxicidade , Ratos , Ratos Wistar , Propriedades de Superfície
16.
Nanoscale ; 11(13): 6489-6496, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30892348

RESUMO

Multifunctional nanoparticles with a magnetic core and gold shell structures are emerging multi-modal imaging probes for disease diagnosis, image-guided therapy, and theranostic applications. Owing to their multi-functional magnetic and plasmonic properties, these nanoparticles can be used as contrast agents in multiple complementary imaging modalities. Magnetic particle imaging (MPI) is a new pre-clinical imaging system that enables real-time imaging with high sensitivity and spatial resolution by detecting the dynamic responses of nanoparticle tracers. In this study, we evaluated the dynamic magnetic properties and MPI imaging performances of core-shell nanoparticles with a magnetic core coated with a gold shell. A change in AC hysteresis loops was detected before and after the formation of the gold shell on magnetic core nanoparticles, suggesting the influence of the core-shell interfacial effect on their dynamic magnetic properties. This alteration in the dynamic responses resulted in an enhancement of the MPI imaging capacity of magnetic nanoparticles. The gold shell coating also enabled a simple and effective functionalization of the nanoparticles with a brain glioma targeting ligand. The enhanced MPI imaging capacity and effective functionality suggest the potential application of the magnetic-gold core-shell nanoparticles for MPI disease diagnostics.


Assuntos
Ouro/química , Nanopartículas de Magnetita/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cloretos/química , Meios de Contraste/química , Compostos Férricos/química , Humanos , Nanopartículas de Magnetita/toxicidade , Microscopia Eletrônica de Transmissão , Compostos de Sulfidrila/química
17.
J Nanobiotechnology ; 17(1): 27, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728022

RESUMO

BACKGROUND: Theranostics application of superparamagnetic nanoparticles based on magnetite and maghemite is impeded by their toxicity. The use of additional protective shells significantly reduced the magnetic properties of the nanoparticles. Therefore, iron carbides and pure iron nanoparticles coated with multiple layers of onion-like carbon sheath seem to be optimal for biomedicine. Fluorescent markers associated with magnetic nanoparticles provide reliable means for their multimodal visualization. Here, biocompatibility of iron nanoparticles coated with graphite-like shell and labeled with Alexa 647 fluorescent marker has been investigated. METHODS: Iron core nanoparticles with intact carbon shells were purified by magnetoseparation after hydrochloric acid treatment. The structure of the NPs (nanoparticles) was examined with a high resolution electron microscopy. The surface of the NPs was alkylcarboxylated and further aminated for covalent linking with Alexa Fluor 647 fluorochrome to produce modified fluorescent magnetic nanoparticles (MFMNPs). Live fluorescent imaging and correlative light-electron microscopy were used to study the NPs intracellular distribution and the effects of constant magnetic field on internalized NPs in the cell culture were analyzed. Cell viability was assayed by measuring a proliferative pool with Click-IT labeling. RESULTS: The microstructure and magnetic properties of superparamagnetic Fe@C core-shell NPs as well as their endocytosis by living tumor cells, and behavior inside the cells in constant magnetic field (150 mT) were studied. Correlative light-electron microscopy demonstrated that NPs retained their microstructure after internalization by the living cells. Application of constant magnetic field caused orientation of internalized NPs along power lines thus demonstrating their magnetocontrollability. Carbon onion-like shells make these NPs biocompatible and enable long-term observation with confocal microscope. It was found that iron core of NPs shows no toxic effect on the cell physiology, does not inhibit the cell proliferation and also does not induce apoptosis. CONCLUSIONS: Non-toxic, biologically compatible superparamagnetic fluorescent MFMNPs can be further used for biological application such as delivery of biologically active compounds both inside the cell and inside the whole organism, magnetic separation, and magnetic resonance imaging (MRI) diagnostics.


Assuntos
Rastreamento de Células/métodos , Corantes Fluorescentes/química , Nanopartículas de Magnetita/química , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Endocitose , Óxido Ferroso-Férrico/química , Grafite/química , Humanos , Luz , Campos Magnéticos , Nanopartículas de Magnetita/toxicidade , Imagem Óptica/métodos , Tamanho da Partícula , Propriedades de Superfície
18.
Part Fibre Toxicol ; 16(1): 8, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760282

RESUMO

BACKGROUND: It is well established that toxicological evaluation of engineered nanomaterials (NMs) is vital to ensure the health and safety of those exposed to them. Further, there is a distinct need for the development of advanced physiologically relevant in vitro techniques for NM hazard prediction due to the limited predictive power of current in vitro models and the unsustainability of conducting nano-safety evaluations in vivo. Thus, the purpose of this study was to develop alternative in vitro approaches to assess the potential of NMs to induce genotoxicity by secondary mechanisms. RESULTS: This was first undertaken by a conditioned media-based technique, whereby cell culture media was transferred from differentiated THP-1 (dTHP-1) macrophages treated with γ-Fe2O3 or Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs) to the bronchial cell line 16HBE14o-. Secondly construction and SPION treatment of a co-culture model comprising of 16HBE14o- cells and dTHP-1 macrophages. For both of these approaches no cytotoxicity was detected and chromosomal damage was evaluated by the in vitro micronucleus assay. Genotoxicity assessment was also performed using 16HBE14o- monocultures, which demonstrated only γ-Fe2O3 nanoparticles to be capable of inducing chromosomal damage. In contrast, immune cell conditioned media and dual cell co-culture SPION treatments showed both SPION types to be genotoxic to 16HBE14o- cells due to secondary genotoxicity promoted by SPION-immune cell interaction. CONCLUSIONS: The findings of the present study demonstrate that the approach of using single in vitro cell test systems precludes the ability to consider secondary genotoxic mechanisms. Consequently, the use of multi-cell type models is preferable as they better mimic the in vivo environment and thus offer the potential to enhance understanding and detection of a wider breadth of potential damage induced by NMs.


Assuntos
Dano ao DNA , Compostos Férricos/toxicidade , Nanopartículas de Magnetita/toxicidade , Testes de Mutagenicidade/métodos , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Brônquios/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Meios de Cultivo Condicionados , Citocinas/biossíntese , Endocitose/efeitos dos fármacos , Humanos , Técnicas In Vitro , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Células THP-1
19.
Colloids Surf B Biointerfaces ; 177: 253-259, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30763790

RESUMO

Magnetic nanoparticles (MNPs) represent one of the greatest promises for the development of a new generation of diagnostic agents for magnetic resonance imaging, with improved specificity and safety. Indeed, during the last decade the number of studies published in this field has grown exponentially. However, the clinical translation achieved so far has been very limited. This situation is likely related to the fact that most studies are focused on the in vitro characterization of these new nanomaterials, and very few provide an exhaustive in vivo characterization, where key aspects, such as pharmacokinetics, bioavailability, and, most importantly, toxicity, are properly evaluated. In this work, we propose a protocol for the comprehensive assessment of the toxicity of MNPs, based on the use of zebrafish embryos as an intermediate screening step between cell culture assays and studies in rodents. MNPs with different cores, ferrite and manganese ferrite oxide, and sizes between 3 and 20 nm, were evaluated. Cell viability at a concentration of 50 µg/mL of PEGylated MNPs was above 90 % in all cases. However, the exposure of zebrafish embryos to manganese based MNPs at concentrations above 100 µg/mL showed a low survival rate (<50 %). In contrast, no mortality (survival rate ∼100 %) and normal hatching rate were obtained for the iron oxide MNPs. Based on these results, together with the physicochemical and magnetic properties (r2 = 153.6 mM-1·s-1), the PEGylated 20 nm cubic shape iron oxide MNPs were selected and tested in mice, showing very good MRI contrast and, as expected, absence of toxicity.


Assuntos
Meios de Contraste/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Compostos Férricos/toxicidade , Nanopartículas de Magnetita/toxicidade , Polietilenoglicóis/toxicidade , Animais , Sobrevivência Celular , Células Cultivadas , Meios de Contraste/química , Relação Dose-Resposta a Droga , Compostos Férricos/química , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Tamanho da Partícula , Polietilenoglicóis/química , Propriedades de Superfície , Peixe-Zebra/embriologia
20.
Life Sci ; 220: 156-161, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30716338

RESUMO

Magnetic nanoparticles (MNPs) are promising candidates for drug delivery and treatment of various disorders. Toxicity evaluation is a critical point in the development of nanoformulations and therefore, draws considerable attention. Formulations involving individual or combinatorial nanoparticle suspensions might be used for targeted delivery and treatment. This might be a evaluated further for safety related issues considering future medications based on MNPs. Nanoparticle distribution in the body is dependent on its surface characteristics. Size, dose and routes of nanoparticle entry have to be taken into consideration for future assays.


Assuntos
Nanopartículas de Magnetita/toxicidade , Nanopartículas/efeitos adversos , Animais , Sistemas de Liberação de Medicamentos/efeitos adversos , Humanos , Nanopartículas de Magnetita/efeitos adversos , Nanopartículas/toxicidade , Preparações Farmacêuticas
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