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1.
Int J Nanomedicine ; 14: 7549-7560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571863

RESUMO

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment. Methods: We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice. Results: The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid. Conclusion: These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.


Assuntos
Apoptose , Receptores de Hialuronatos/metabolismo , Campos Magnéticos , Nanopartículas de Magnetita/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Endocitose , Regulação Neoplásica da Expressão Gênica , Humanos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
2.
Int J Nanomedicine ; 14: 7879-7889, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576129

RESUMO

Introduction and objective: Precisely and sensitively diagnosing diseases especially early and accurate tumor diagnosis in clinical magnetic resonance (MR) scanner is a highly demanding but challenging task. Gadolinium (Gd) chelate is the most common T 1 magnetic resonance imaging (MRI) contrast agent at present. However, traditional Gd-chelates are suffering from low relaxivity, which hampers its application in clinical diagnosis. Currently, the development of nano-sized Gd based T 1 contrast agent, such as incorporating gadolinium chelate into nanocarriers, is an attractive and feasible strategy to enhance the T 1 contrast capacity of Gd chelate. The objective of this study is to improve the T 1 contrast ability of Gd-chelate by synthesizing nanoparticles (NPs) for accurate and early diagnosis in clinical diseases. Methods: Reverse microemulsion method was used to coat iron oxide (IO) with tunable silica shell and form cores of NPs IO@SiO2 at step one, then Gd-chelate was loaded on the surface of silica-coated iron oxide NPs. Finally, Gd-based silica coating magnetite NPs IO@SiO2-DTPA-Gd was developed and tested the ability to detect tumor cells on the cellular and in vivo level. Results: The r 1 value of IO@SiO2-DTPA-Gd NPs with the silica shell thickness of 12 nm was about 33.6 mM-1s-1, which was approximately 6 times higher than Gd-DTPA, and based on its high T 1 contrast ability, IO@SiO2-DTPA-Gd NPs could effectively detect tumor cells on the cellular and in vivo level. Conclusion: Our findings revealed the improvement of T 1 relaxation was not only because of the increase of molecular tumbling time caused by the IO@SiO2 nanocarrier but also the generated magnetic field caused by the IO core. This nanostructure with high T 1 contrast ability may open a new approach to construct high-performance T 1 contrast agent.


Assuntos
Quelantes/química , Materiais Revestidos Biocompatíveis/química , Gadolínio/química , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Dióxido de Silício/química , Animais , Morte Celular , Meios de Contraste/química , Feminino , Compostos Férricos/química , Gadolínio DTPA/química , Células HeLa , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular
3.
Int J Nanomedicine ; 14: 6481-6495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496698

RESUMO

Background: Despite the numerous pharmacological activities of quercetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. In the present study, we fabricated a novel form of quercetin-conjugated Fe3O4-ß-cyclodextrin (ßCD) nanoparticles (NPs), and the effect of these prepared NPs was evaluated in a chronic model of epilepsy. Methods: Quercetin-loaded NPs were prepared using an iron oxide core coated with ßCD and pluronic F68 polymer. The chronic model of epilepsy was developed by intraperitoneal injection of pentylenetetrazole (PTZ) at dose of 36.5 mg/kg every second day. Quercetin or its nanoformulation at doses of 25 or 50 mg/kg were administered intraperitoneally 10 days before PTZ injections and their applications continued 1 hour before each PTZ injection. Immunostaining was performed to evaluate the neuronal density and astrocyte activation of hippocampi. Results: Our data showed successful fabrication of quercetin onto Fe3O4-ßCD NPs. In comparison to free quercetin, quercetin NPs markedly reduced seizure behavior, neuronal loss, and astrocyte activation in a PTZ-induced kindling model. Conclusion: Overall, quercetin-Fe3O4-ßCD NPs might be regarded as an ideal therapeutic approach in epilepsy disorder.


Assuntos
Epilepsia/tratamento farmacológico , Nanopartículas de Magnetita/química , Quercetina/uso terapêutico , beta-Ciclodextrinas/química , Animais , Astrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/patologia , Excitação Neurológica , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Pentilenotetrazol/administração & dosagem , Quercetina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Life Sci ; 234: 116787, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445028

RESUMO

Iron deficiency anemia (IDA) is a major worldwide public health problem. This is due to its prevalence among infants, children, adolescents, pregnant and reproductive age women. Ferrous sulfate (FeSO4) is the first line therapy for iron IDA. Unfortunately, it is reported that FeSO4 suffers from low absorption rate in the body and itself exhibits severe side effects. Herein, iron oxide magnetic nanoparticles-loaded liposomes (LMNPs) are prepared, characterized and evaluated as a treatment regimen for IDA in Wistar rats (as an animal model). Iron oxide magnetic nanoparticles (MNPs) are prepared and loaded into liposomes using the thin film hydration method. The size of the prepared formulations is in the range 10-100 nm, thus it can avoid the reticular endothelial system (RES), and increased their blood circulation time. For in vivo assessment, thirty-five Wistar rats are divided into 5 groups (n = 7): negative control group, positive control group, and three groups treated with different iron formulations (FeSO4, MNPs and LMNPs). Anemia is induced in the anemic groups by the bleeding method and then treatment started with different iron compounds administrated orally for 13 days. Hematological parameters are followed up during the treatment period. Results indicate that, in the LMNPs group, the hematological parameters turn to normal values and the histopathological structures of the liver, spleen and kidney remain normal. This proves that liposome increases the bioavailability of MNPs. In conclusion, LMNPs demonstrate superiority as a therapeutic regimen for the treatment of IDA among the tested iron formulations.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Ferrosos/administração & dosagem , Hematínicos/administração & dosagem , Lipossomos/química , Nanopartículas de Magnetita/química , Anemia Ferropriva/sangue , Animais , Disponibilidade Biológica , Feminino , Compostos Ferrosos/farmacocinética , Compostos Ferrosos/uso terapêutico , Hematínicos/farmacocinética , Hematínicos/uso terapêutico , Hemoglobinas/análise , Lipossomos/ultraestrutura , Nanopartículas de Magnetita/ultraestrutura , Ratos Wistar
5.
Int J Nanomedicine ; 14: 4397-4412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417251

RESUMO

Background: Graphene magnetite nanocomposites (G/Fe3O4) exhibit light photothermal conversion upon enhancement by 808 nm IR laser excitation. We evaluated the cytotoxic and photothermal effects of G/Fe3O4 on a HepG2 human liver cancer cell model. Methods: Graphene nanosheets (rGO), magnetite nanoparticles (Fe3O4), and G/Fe3O4 were prepared by chemical methods and characterized using transmission electron microscopy, Raman spectroscopy, zeta analysis, and vibrating sample magnemeter. Dark and light cytotoxicity were screened with colorimetric Sulforhodamine B cell viability assay after 24 and 48 hours. DNA fragmentation and some apoptotic genes on a transcriptional RNA level expression were performed. All prepared nanomaterials were evaluated for their photothermal effect at concentrations of 10 and 50 µg/mL. The power density incident on the cells by 300 mW 808 IR diode laser was 0.597 W/cm2. Results: Treatment of HepG2 with 400 µg/mL of rGO, Fe3O4, and G/Fe3O4 showed alteration in cell morphology after 24 hours of cell treatment and revealed toxic effects on cellular DNA. Evaluation of the cytotoxic effects showed messenger RNA (mRNA) in ß-actin and Bax apoptotic genes, but no expression of mRNA of caspase-3 after 24 hours of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway. A photothermal effect was observed for G/Fe3O4 after irradiation of the HepG2 cells. A marked decrease was found in cell viability when treated with 10 and 50 µg/mL G/Fe3O4 from 40% to 5% after 48 hours of cell treatment. Conclusion: Results indicate that G/Fe3O4 nanocomposite was effective at transformation of light into heat and is a promising candidate for cancer therapy.


Assuntos
Grafite/química , Hipertermia Induzida , Raios Infravermelhos , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/química , Modelos Biológicos , Nanocompostos/química , Fototerapia , Apoptose/genética , Sobrevivência Celular/genética , Fragmentação do DNA , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/ultraestrutura , Nanocompostos/ultraestrutura , Oxirredução , Análise Espectral Raman , Eletricidade Estática , Difração de Raios X
6.
Int J Nanomedicine ; 14: 5785-5797, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440047

RESUMO

Introduction: The targeted delivery of anti-cancer drugs to tumor tissue has been recognized as a promising strategy to increase their therapeutic efficacy and reduce side effects. Mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles (NH2-MSNs), a kind of nanocarrier, can passively enter tumor tissues to enhance the permeability and retention of drugs. However, NH2-MSNs do not specifically bind to cancer cells. This drawback encouraged us to develop a more efficient nanocarrier for cancer therapy. Methods: Herein, we describe the development of an effective nanocarrier based on NH2-MSNs, which were modified with hyaluronic acid on their surface (HA-MSNs) and loaded with doxorubicin (DOX). We have successfully fabricated uniform spherical HA-MSNs nanocarriers. The targeting ability of this delivery system was evaluated through specific uptake by cells and IVIS imaging. Results: DOX-HA-MSNs nanocarriers displayed more dramatic cytotoxic activity against 4T1 breast cancer cells compared to GES-1 gastric mucosa cells. In vivo results revealed that once DOX-HA-MSNs nanocarriers are exposed to an external magnetic field, they could be rapidly attracted to the magnet and effectively cross the cytoplasmic membrane via CD44 receptor-mediated transcytosis. This allows them to access the cancer cell cytoplasm and release DOX based on changes in the physiological environment. Both in vitro and in vivo results demonstrated that the HA-MSNs nanocarriers provided better therapeutic efficacy. Conclusion: The HA-MSNs nanocarriers represent an effective new paradigm to treat cancers due to active targeting to the tumor cells. Moreover, the specific uptake by the tumor effectively protects normal tissues to reduce off-target side effects. The reported findings support further investigation of HA-MSNs for cancer therapy.


Assuntos
Dextranos/química , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Nanopartículas de Magnetita/química , Dióxido de Silício/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Espectroscopia Fotoeletrônica , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Ensaios Antitumorais Modelo de Xenoenxerto
7.
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
8.
Anal Bioanal Chem ; 411(25): 6733-6743, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402423

RESUMO

An immunomagnetic optical probe based on a core/shell magnetic nanoparticle-quantum dot was fabricated for detection of Streptococcus agalactiae, the causative agent of pneumonia and meningitis in newborns. The silica-coated magnetic nanoparticles conjugated with anti-S. agalactiae monoclonal antibody provided high specificity for pre-enrichment of bacteria from biological samples with a complex matrix such as milk. Compared with conventional methods such as culture and molecular techniques, the combination of fluorescent quantum dot and magnetic nanoparticle enhanced the sensitivity and speed of bacterial identification. The bio-functionalized fluorescent-magnetic nanoparticles were characterized by TEM, SEM, VSM, XRD, DLS, and FTIR and applied to the detection of S. agalactiae with a limit of 10 and 102 CFU/mL in PBS and milk, respectively. This immunomagnetic optical probe can be used for rapid isolation, sensitive, and specific detection of targeted bacteria without any treatment in clinical and animal samples in the presence of other infectious agents.


Assuntos
Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Nanopartículas de Magnetita/química , Leite/microbiologia , Streptococcus agalactiae/isolamento & purificação , Animais , Anticorpos Imobilizados/química , Análise de Alimentos/métodos , Separação Imunomagnética/métodos , Nanopartículas de Magnetita/ultraestrutura , Microscopia de Fluorescência/métodos , Pontos Quânticos/química , Pontos Quânticos/ultraestrutura , Dióxido de Silício/química , Espectrometria de Fluorescência/métodos , Infecções Estreptocócicas/microbiologia
9.
Int J Nanomedicine ; 14: 4319-4331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354263

RESUMO

Objective: The study aimed to synthesize superparamagnetic NaYF4:Yb,Er@PE3@Fe3O4 upconversion nanoprobes and to study their photothermal effects for the treatment of malignant melanoma. Methods: Morphological characteristics of the synthesized nanoprobes were examined by scanning electron microscopy. Their biocompatibility and biodistribution profiles were assessed through blood routine/biochemistry tests and the inductively coupled plasma/optical emission spectrometry-based analysis of tissue metal elements. Their photothermal conversion efficiency and their potential as contrast agents for upconversion luminescence (UCL)/magnetic resonance imaging (MRI) dual-modal imaging were tested. Efficacy in photothermal therapy, which was achieved by combining nanoprobes with near-infrared (NIR) irradiation, was evaluated in both A375 cell line and BALB/c mice models. The underlying mechanisms were interrogated by molecular approaches including the MTT assay, flow cytometry, semiquantitative PCR, western blot, and immunohistochemistry. Results: 1) Our synthesized NaYF4:Yb,Er@PE3@Fe3O4 nanoprobes exhibited a uniform cubic morphology with a diameter of ~50 nm. Subcutaneous administration led to no severe, long-lasting adverse effects in mice, possibly due to complete removal of these nanomaterials within one month. 2) Our nanoprobes possessed superior photothermal conversion efficiency and strong contrasting effects during UCL/MRI dual-modal imaging, corroborating their applications in imaging-guided photothermal therapy. 3) Combinatorial treatment of these nanoprobes with NIR irradiation induced profound apoptosis/necrosis in A375 cells. Similarly, the same treatment modality led to strong therapeutic effects in BALB/c mice implanted with A375 tumor xenografts. Mechanistic studies suggested an involvement of heat shock protein 70 in mediating the observed antitumor effects of our nanoprobes. Conclusion: Our study describes a convenient method to synthesize a new type of superparamagnetic upconversion nanoprobes, which possess high biocompatibility and can be used in imaging-guided photothermal therapy for the treatment of malignant melanoma. Importantly, our findings will promote clinical applications of NaYF4:Yb,Er@PE3@Fe3O4 as novel theranostic agents in treating melanoma and many other tumors.


Assuntos
Érbio/química , Fluoretos/química , Hipertermia Induzida , Nanopartículas de Magnetita/uso terapêutico , Melanoma/terapia , Fototerapia , Ítrio/química , Animais , Linhagem Celular Tumoral , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Raios Infravermelhos , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/ultraestrutura , Melanoma/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual , Carga Tumoral
10.
Int J Nanomedicine ; 14: 4517-4528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354271

RESUMO

Purpose: We developed a contrast agent for targeting E-selectin expression. We detected the agent using magnetic resonance imaging (MRI) in vivo in nude mice that had undergone nasopharyngeal carcinoma (NPC) metastasis. Methods: Sialyl Lewis X (sLeX) was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Hydrodynamic size, polydispersity index, and ζ-potential of USPIO-polyethylene glycol (PEG) nanoparticles and USPIO-PEG-sLeX nanoparticles were measured. Component changes in nanoparticles of USPIO, USPIO-PEG, and USPIO-PEG-sLeX were analyzed by thermogravimetric analysis and Fourier-transform infrared spectroscopy. A model of NPC metastasis to inguinal lymph nodes in nude mice was used to investigate characteristics of the USPIO-PEG-sLeX nanoparticles in vivo. We investigated the ability of the T2* value, change in T2* value (ΔT2* value), and enhancement rate (ER) to assess accumulation of USPIO-PEG-sLeX nanoparticles quantitatively in mice of a metastasis group and control group. Four MRI scans were undertaken for each mouse. The first scan (t0) was done before administration of USPIO-PEG-sLeX nanoparticles (0.1 mL) via the tail vein. The other scans were carried out at 0 (t1), 1 (t2), and 2 hours (t3) postinjection. The mean optical density was used to reflect E-selectin expression. Results: sLeX was labeled onto USPIO successfully. In vivo, there were significant interactions between the groups and time for T2* values after administration of USPIO-PEG-sLeX nanoparticles. Six parameters (T2* at t2, ΔT2* at t1, ΔT2* at t2, ER at t1, ER at t2, and ER at t3) were correlated with the mean optical density. Conclusion: USPIO-PEG-sLeX nanoparticles can be used to assess E-selectin expression quantitatively. Use of such molecular probes could enable detection of early metastasis of NPC, more accurate staging, and treatment monitoring.


Assuntos
Dextranos/química , Selectina E/metabolismo , Nanopartículas de Magnetita/química , Animais , Linhagem Celular Tumoral , Dextranos/ultraestrutura , Difusão Dinâmica da Luz , Feminino , Metástase Linfática , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Oligossacarídeos/metabolismo , Polietilenoglicóis/química , Eletricidade Estática , Termodinâmica
11.
Mater Sci Eng C Mater Biol Appl ; 102: 124-133, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146983

RESUMO

Novel theranostic nanoplatform is expected to integrate imaging for guiding and monitoring of the tumor therapy with great therapeutic efficacy and fewer side effects. Here we describe the preparation of a multifunctional 99mTc-bisphosphonate-coated magnetic nanoparticles (MNPs) based on Fe3O4 and coated with two hydrophilic bisphosphonate ligands, i.e., methylene diphosphonate (MDP) and 1-hydroxyethane-1,1- diphosphonate (HEDP). The presence of the bisphosphonates on the MNPs surface, enabled their biocompatibility, colloidal stability and successful binding of the radionuclide. The morphology, size, structure, surface charge and magnetic properties of obtained bisphosphonate-coated Fe3O4 MNPs were characterized by transmission electron microscopy, X-ray powder diffraction, dynamic light scattering, laser Doppler electrophoresis, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The specific power absorption values for Fe3O4-MDP and Fe3O4-HEDP were 113 W/g and 141 W/g, respectively, indicated their heating ability under applied magnetic field. Coated MNPs were radiolabeled with 99mTc using stannous chloride as the reducing agent in a reproducible high yield (95% for Fe3O4-MDP and 97% for Fe3O4-HEDP MNPs) and were remained stable in saline and human serum for 24 h. Ex vivo biodistribution studies presented significant liver and spleen uptake in healthy Wistar rats after intravenous administration at all examined time points due to the colloidal nature of both 99mTc-MNPs. Results of scintigraphy studies are in accordance with ex vivo biodistribution studies, demonstrating high in vivo stability of radiolabeled MNPs and therefore results of both methods were proved as accurate information on the biodistribution profile of investigated MNPs. Overall, in vitro and in vivo stability as well as heating ability, indicate that biocompatible radiolabeled bisphosphonate magnetic nanoparticles exhibit promising potential as a theranostic nanoagent.


Assuntos
Materiais Revestidos Biocompatíveis/química , Difosfonatos/química , Nanopartículas de Magnetita/química , Compostos de Organotecnécio/química , Nanomedicina Teranóstica , Animais , Hipertermia Induzida , Nanopartículas de Magnetita/ultraestrutura , Masculino , Tamanho da Partícula , Ratos Wistar , Temperatura Ambiente , Fatores de Tempo , Distribuição Tecidual , Difração de Raios X
12.
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
13.
Int J Nanomedicine ; 14: 3375-3388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123402

RESUMO

Background: Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose: To fill part of this gap, this work aimed to investigate biocompatibility and bio-distribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods: NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results: NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion: Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals' age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population.


Assuntos
Envelhecimento/fisiologia , Ácido Cítrico/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Nanopartículas de Magnetita/química , Animais , Feminino , Ferro/química , Pulmão/efeitos dos fármacos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Óxido Nítrico/sangue , Especificidade de Órgãos/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
14.
Int J Nanomedicine ; 14: 2719-2731, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114192

RESUMO

Background: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive. Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs. Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced. Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.


Assuntos
Neoplasias do Endométrio/patologia , Regulação Neoplásica da Expressão Gênica , Nanopartículas de Magnetita/química , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Animais , Sequência de Bases , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/irrigação sanguínea , Feminino , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais
15.
Molecules ; 24(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109114

RESUMO

Human serum albumin (HSA) is one of the most frequently immobilized proteins on the surface of carriers, including magnetic nanoparticles. This is because the drug-HSA interaction study is one of the basic pharmacokinetic parameters determined for drugs. In spite of many works describing the immobilization of HSA and the binding of active substances, research describing the influence of the used support on the effectiveness of immobilization is missing. There are also no reports about the effect of the support drying method on the effectiveness of protein immobilization. This paper examines the effect of both the method of functionalizing the polymer coating covering magnetic nanoparticles (MNPs), and the drying methods for the immobilization of HSA. Albumin was immobilized on three types of aminated chitosan-coated nanoparticles with a different content of amino groups long distanced from the surface Fe3O4-CS-Et(NH2)1-3. The obtained results showed that both the synthesis method and the method of drying nanoparticles have a large impact on the effectiveness of immobilization. Due to the fact that the results obtained for Fe3O4-CS-Et(NH2)2 significantly differ from those obtained for the others, the influence of the geometry of the shell structure on the ability to bind HSA was also explained by molecular dynamics.


Assuntos
Quitosana/química , Materiais Revestidos Biocompatíveis , Proteínas Imobilizadas , Nanopartículas de Magnetita , Albumina Sérica Humana , Adsorção , Aminação , Humanos , Proteínas Imobilizadas/química , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Modelos Moleculares , Modelos Teóricos , Conformação Molecular , Polímeros/química , Albumina Sérica Humana/química , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier
16.
ACS Appl Mater Interfaces ; 11(21): 19495-19505, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31058488

RESUMO

Rapid and early diagnosis of respiratory viruses is key to preventing infections from spreading and guiding treatments. Here, we developed a sensitive and quantitative surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFIA) strip for simultaneous detection of influenza A H1N1 virus and human adenovirus (HAdV) by using Fe3O4@Ag nanoparticles as magnetic SERS nanotags. The new type of Fe3O4@Ag magnetic tags, which were conjugated with dual-layer Raman dye molecules and target virus-capture antibodies, performs the following functions: specific recognition and magnetic enrichment of target viruses in the solution and SERS detection of the viruses on the strip. Based on this strategy, the magnetic SERS strip can directly be used for real biological samples without any sample pretreatment steps. The limits of detection for H1N1 and HAdV were 50 and 10 pfu/mL, respectively, which were 2000 times more sensitive than those from the standard colloidal gold strip method. Moreover, the proposed strip is easy to operate, rapid, stable, and can achieve high throughput and is thus a potential tool for early detection of virus infection.


Assuntos
Adenovírus Humanos/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Magnetismo , Análise Espectral Raman , Anticorpos/metabolismo , Coloides/química , Compostos Férricos/química , Ouro/química , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Sensibilidade e Especificidade , Prata/química
17.
Int J Nanomedicine ; 14: 2591-2605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040674

RESUMO

Introduction: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. Methods: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BN-TMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. Results: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (>74% cell viability) and high affinity (IC50=8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99mTc-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. Conclusion: 68Ga-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.


Assuntos
Bombesina/química , Quitosana/química , Radioisótopos de Gálio/química , Nanopartículas de Magnetita/química , Imagem Molecular/métodos , Animais , Ligação Competitiva , Bombesina/sangue , Bombesina/síntese química , Morte Celular , Linhagem Celular Tumoral , Quitosana/síntese química , Feminino , Humanos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Camundongos Nus , Tamanho da Partícula , Tomografia por Emissão de Pósitrons , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Distribuição Tecidual , Difração de Raios X
18.
Int J Nanomedicine ; 14: 2619-2636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043778

RESUMO

Background: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems has opened a new window to overcome these problems. There has been a strong interest development of new platform and system for delivof chemotherapeutic agents. Purpose: In the present study, a green synthesis method was chosen and performed for preparation of a novel amphoteric calix[4]arene (Calix) macrocycle with low toxicity to the human body. Materials and methods: The amphoteric Calix was coated on the surface of Fe3O4 magnetic nanoparticles and used as a magnetic nanocarrier for simultaneous delivery of two anticancer agents, doxorubicin and methotrexate, against MCF7 cancer cells. Several chemical characterizations were done for validation of prepared nanocarrier, and in vitro loading and release studies of drugs were performed with good encapsulation efficiency. Results: In vitro biological studies including hemolysis assay, erythrocytes sedimentation rate, red blood cells aggregation, cyto cellular internalization, and apoptosis evaluations were performed. Based on results, the developed nanocarrier has many advantages and capability for an efficient codelivery of DOX and MTX, which has a highly potent ability to kill cancer cells. Conclusion: All these results persuade us, this nanocarrier could be effectively used for cancer therapy of MCF7 breast cancer cells and is suitable for use in further animal studies in future investigations.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Calixarenos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Fenóis/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Calixarenos/síntese química , Varredura Diferencial de Calorimetria , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Difusão Dinâmica da Luz , Endocitose , Feminino , Humanos , Células MCF-7 , Nanopartículas de Magnetita/ultraestrutura , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Tamanho da Partícula , Fenóis/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Int J Nanomedicine ; 14: 3235-3244, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118633

RESUMO

Purpose: Here, we present the successful preparation of a highly efficient gallic acid resin grafted with magnetic nanoparticles (MNPs) and containing a branched brush polymeric shell. Methods: Using a convenient co-precipitation method, we prepared Fe3O4 nanoparticles stabilized by citric acid. These nanoparticles underwent further silica modification and amino functionalization followed by gallic acid functionalization on their surface. Under alkaline conditions, we used a condensation reaction that combined formaldehyde and gallic, to graft the gallic acid-formaldehyde resin on the surface. We then evaluated the polymer-grafted MNPs to assay the Candida Antarctica B lipase(Cal-B) immobilization via physical adsorption. Conclusion: Furthermore, during optimization of parameters that defined conditions of immobilization, we found that the optimum immobilization was achieved in 15 mins. Also, optimal immobilization temperature and pH were 38ºC and 7.5, respectively. In addition, the reusability study of immobilized lipase polymer-grafted MNPs was done by isolating the MNPs from the reaction medium using magnetic separation, which showed that grafted MNPs reached 5 cycles with 91% activity retention.


Assuntos
Enzimas Imobilizadas/metabolismo , Compostos Férricos/química , Proteínas Fúngicas/metabolismo , Ácido Gálico/química , Lipase/metabolismo , Nanopartículas de Magnetita/química , Resinas Sintéticas/química , Adsorção , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/ultraestrutura , Polímeros , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Termogravimetria , Fatores de Tempo , Difração de Raios X
20.
J Basic Microbiol ; 59(6): 569-578, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30980727

RESUMO

The biocompatible-coated iron oxide nanoparticles (IONs) have attracted a great interest because of their various applications in biological science and medicine. In most cases, the toxic effect of naked iron oxide nanoparticles is completely cleared by adding a biocompatible coating, such as polysaccharides, polyethylene glycol (PEG), or biosynthesis of biocompatible-coated IONs using microorganisms such as bacteria. In the present study, polysaccharide-coated iron oxide nanoparticles were produced by a strain of Staphylococcus warneri isolated from a thermal spring. For identification of the isolated bacterium, 16S rRNA gene sequencing was done. Characterization of the nanoparticles was performed for the first time, using transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), X-ray crystallography (XRD), Fourier-transform infrared (FTIR) spectroscopy, vibrating sample magnetometer (VSM), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results indicated that the spherical iron oxide nanoparticles were coated by a polysaccharide (13.6%), which provided a large negative charge of -91 mV and very low saturation magnetization of around 0.28 emu/g. The result of MTT assay on MOLT-4 cell lines showed that the percentage of viability was between 95.6% and 68.9% in the 10-100 µM of nanoparticle concentrations with a high IC 50 value, which makes it appropriate for biomedical applications such as cancer therapy.


Assuntos
Materiais Biocompatíveis/química , Fontes Termais/microbiologia , Nanopartículas de Magnetita/química , Polissacarídeos Bacterianos/química , Staphylococcus/metabolismo , Materiais Biocompatíveis/isolamento & purificação , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Campos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Tamanho da Partícula , Polissacarídeos Bacterianos/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Staphylococcus/classificação , Staphylococcus/genética , Staphylococcus/isolamento & purificação
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