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1.
Nat Commun ; 11(1): 3903, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764543

RESUMO

Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI (<1 ng/mL) with high specificity and reproducibility, while simultaneously depleting highly abundant proteins such as human serum albumin (>1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.


Assuntos
Análise Química do Sangue/métodos , Proteínas Sanguíneas/análise , Espectrometria de Massas/métodos , Proteômica/métodos , Troponina I/sangue , Biomarcadores/sangue , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia , Processamento de Proteína Pós-Traducional , Proteoma/análise , Reprodutibilidade dos Testes , Albumina Sérica Humana/análise
2.
Int J Nanomedicine ; 15: 4573-4589, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606693

RESUMO

Background: Therapeutic efficiency of ceragenins against cancers may be limited by lack of their hemocompatibility when high concentrations of molecules are required to reach a desired result. Synergistic effects observed upon administration of anticancer agents and metal nanoparticles may provide an opportunity to limit toxicity of immobilized ceragenins on the surface of metal nanoparticles and to improve their therapeutic efficiency at the same time. The aim of present work is to investigate the anticancer activities and hemocompatibility of nanoformulations consisting of ceragenin CSA-131 united with aminosilane-modified iron oxide-based magnetic nanoparticles (MNP) and prepared by 1) covalent bonding (MNP@CSA-131) or 2) by combining CSA-131 with MNP in 1:1 ratio (CSA-131 + MNP). Possible synergistic interactions between CSA-131 and magnetic nanoparticles were also quantified. Methods: MNP@CSA-131 and CSA-131+MNP were tested in vitro against selected lung and colon cancer cells using colorimetric, fluorimetric and flow cytometry methods. Results: Performed analysis demonstrates that MNP-based nanosystems significantly improve the killing efficiency of tested ceragenin, decreasing the viability of extra 1.37±4.72% to 76.07±15.30% cancer cells when compared to free CSA-131. Quantification of synergistic effects indicates the favorable interactions between CSA-131 and magnetic nanoparticles (CI < 1 for all tested doses), revealing at the same time a reduction in effective doses of ceragenin from 1.17 ± 0.61 to 34.57 ± 12.78 times when combined with MNP. We demonstrate that both MNP@CSA-131 and CSA-131+MNP induce significantly apoptosis of cancer cells and prevent the division of colon cancer cells even at relatively low doses of the active compound (10 µg/mL). Importantly, combining CSA-131 with MNP decreases the hemolytic activity of free ceragenin 4.72 to 7.88 times, which indicates a considerable improvement of hemotoxicity profile. Conclusion: Comparative analyses have revealed that both developed CSA-containing nanoformulations due to the utility of synergistic interactions between MNP and CSA-131, which are effective against lung and colon cancer cells. This indicates the new directions in preparation of MNP-based therapeutics, which are relatively easy to synthetize, cost-effective and safe when intravenously administrated.


Assuntos
Compostos Férricos/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Esteroides/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/patologia , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Teste de Materiais
3.
Int J Nanomedicine ; 15: 3605-3620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547017

RESUMO

Purpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Polímeros/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X , Proteína de Morte Celular Associada a bcl/metabolismo
4.
Int J Nanomedicine ; 15: 3333-3346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494133

RESUMO

Background and Objective: Cancer cells accumulate high concentrations of reactive oxygen species as a result of their faster and uninhibited metabolic activity. Cancer chemotherapeutic agents release an excess of severe adverse reactions as a result of targeting normal cells. This demands an improvement in targeted drug-delivery systems to selectively discharge anticancer drugs in the vicinity of such highly metabolically and mitotically active cells. Materials and Methods: Here, magnetic nanoparticles were synthesized by a traditional co-precipitation technique. Fe3O4@OA-CS-5-FLU-NPs were synthesized by an easy and rapid in situ loading method. The proposed Fe3O4@OA-CS-5-FLU-NPs were productively prepared as well as characterized by various spectroscopic and microscopic studies. Results: The targeted drug release profile of the Fe3O4@OA-CS-5-FLU-NPs was studied in the presence of ROS including H2O2 and pH induction. The released product, Fe3O4@OA-CS-5-FLU-NP, exhibited desirable levels of cytotoxicity and demonstrated morphological changes and inhibition of colony formation for A549 and HeLa S3 cancer cells. The IC50 values at 24 hours were 12.9 and 23 µg/mL, respectively. Conclusion: In summary, results from the MTT assay, fluorescence staining as well as colony formation assays, revealed that the Fe3O4@OA-CS-5-FLU-NPs were active and safe for anticancer biomedical applications. In summary, the present investigation provides a powerful nanostructured based system for improved cancer theranostics that should be further studied.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Nanopartículas de Magnetita/ultraestrutura , Neoplasias/patologia , Ácido Oleico/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
5.
J Chromatogr A ; 1622: 461137, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32414518

RESUMO

In this study, conventional Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method was modified by magnetic solid-phase extraction (MSPE) for purification/pre-concentration of eleven estrogens and estrogen mimics from the extracts of pork and chicken muscles, prior to dansyl chloride (DNS-Cl) derivatization coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay. Dual octadecyl- and 2-aminoethyl-3-aminopropyl- groups functionalized mesoporous silica core-shell magnetic nanoparticles (C18/NH2-Fe3O4@mSiO2 MNPs) were synthesized and employed as MSPE sorbent with remarkable aqueous compatibility in comparison with conventional C18 functionalized sorbent. The proposed MSPE is easier to handle than the traditional SPE purification process in QuEChERS method. The lab-prepared MNPs were characterized by transmission electron microscope (TEM), brunner-emmet-teller (BET), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and vibrating sample magnetometer (VSM). Pre-column derivatization was conducted to significantly enhance the sensitivity of the analytes in MS/MS via analyzing their derivatives in positive ion mode instead of analyzing their original forms in negative ion mode. Under the optimal sample pretreatment and instrumental analysis conditions, the approach showed low limits of detection (LODs, 0.02‒3.00 µg kg-1), appropriate recoveries (81.1‒115.4%) and acceptable precisions (0.48‒15.1%, n = 6), with good feasibility and future prospect of trace compounds analysis in complex food samples.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Estrogênios/análise , Magnetismo , Carne Vermelha/análise , Extração em Fase Sólida/economia , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Adsorção , Animais , Galinhas , Concentração de Íons de Hidrogênio , Limite de Detecção , Nanopartículas de Magnetita/ultraestrutura , Concentração Osmolar , Dióxido de Silício/química , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier , Suínos , Fatores de Tempo
6.
Int J Nanomedicine ; 15: 2583-2603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368042

RESUMO

Introduction: Over the past several years, nano-based therapeutics were an effective cancer drug candidate in order to overcome the persistence of deadliest diseases and prevalence of multiple drug resistance (MDR). Methods: The main objective of our program was to design organosilane-modified Fe3O4/SiO2/APTS(~NH2) core magnetic nanocomposites with functionalized copper-Schiff base complex through the use of (3-aminopropyl)triethoxysilane linker as chemotherapeutics to cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), TEM, and vibrating sample magnetometer (VSM) techniques. All analyses corroborated the successful synthesis of the nanoparticles. In the second step, all compounds of magnetic nanoparticles were validated as antitumor drugs through the conventional MTT assay against K562 (myelogenous leukemia cancer) and apoptosis study by Annexin V/PI and AO/EB. The molecular dynamic simulations of nanoparticles were further carried out; afterwards, the optimization was performed using MM+, semi-empirical (AM1) and Ab Initio (STO-3G), ForciteGemo Opt, Forcite Dynamics, Forcite Energy and CASTEP in Materials studio 2017. Results: The results showed that the anti-cancer activity was barely reduced after modifying the surface of the Fe3O4/SiO2/APTS nanoparticles with 2-hydroxy-3-methoxybenzaldehyde as Schiff base and then Cu(II) complex. The apoptosis study by Annexin V/PI and AO/EB stained cell nuclei was performed that apoptosis percentage of the nanoparticles increased upon increasing the thickness of Fe3O4 shell on the magnetite core. The docking studies of the synthesized compounds were conducted towards the DNA and Topoisomerase II via AutoDock 1.5.6 (The Scripps Research Institute, La Jolla, CA, USA). Conclusion: Results of biology activities and computational modeling demonstrate that nanoparticles were targeted drug delivery system in cancer treatment.


Assuntos
Cobre/química , Compostos Férricos/síntese química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Propilaminas/síntese química , Bases de Schiff/síntese química , Silanos/síntese química , Dióxido de Silício/síntese química , Apoptose , Núcleo Celular/metabolismo , DNA/química , DNA Topoisomerases Tipo II/química , Compostos Férricos/química , Humanos , Células K562 , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Propilaminas/química , Bases de Schiff/química , Silanos/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
7.
Int J Nanomedicine ; 15: 2617-2631, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368044

RESUMO

Introduction: As widely used chemotherapeutic agents, platinum compounds have several therapeutic challenges, such as drug resistance and adverse effects. Theranostic systems, macromolecular or colloidal therapeutics with companion diagnostics, not only address controlled drug delivery but also enable real-time monitoring of tumor sites. Methods: Synthesis of magnetic mesoporous silica nanoparticles (MMSNs) was performed for dual magnetic resonance imaging and drug delivery. MMSN surfaces were modified by imidazoline groups (MMSN-Imi) for cisplatin (Cis-Pt) conjugation via free N-termini to achieve well-controlled drug-release kinetics. Cis-Pt adsorption isotherms and drug-release profile at pH 5 and 7.4 were investigated using inductively coupled plasma atomic emission spectroscopy. Results: MMSN-Imi showed a specific surface area of 517.6 m2 g-1, mean pore diameter of 3.26 nm, and saturated magnetization of 53.63 emu/g. A relatively high r2/r1 relaxivity value was obtained for MMSN-Imi. The nanoparticles provided high Cis-Pt loading with acceptable loading capacity (~30% w:w). Sustained release of Cis-Pt under acidic conditions led to specific inhibitory effects on the growth of human epithelial ovarian carcinoma cells, determined using MTT assays. Dual acridine orange-propidium iodide staining was investigated, confirming induction of apoptosis and necrotic cell death. Conclusion: MMSN-Imi exhibited potential for applications in cancer chemotherapy and combined imaging.


Assuntos
Sistemas de Liberação de Medicamentos , Imidazolinas/química , Nanopartículas de Magnetita/química , Platina/administração & dosagem , Dióxido de Silício/química , Nanomedicina Teranóstica , Adsorção , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Morte Celular , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Hemólise , Humanos , Cinética , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Nitrogênio/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura , Difração de Raios X
8.
J Vis Exp ; (156)2020 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-32116301

RESUMO

A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was synthesized to enhance imaging sensitivity for extrapulmonary tuberculosis (ETB). An SPIO nanoprobe was synthesized and conjugated with MtbsAb. The purified SPIO-MtbsAb nanoprobe was characterized using TEM and NMR. To determine the targeting ability of the probe, SPIO-MtbsAb nanoprobes were incubated with Mtb for in vitro imaging assays and injected into Mtb-inoculated mice for in vivo investigation with magnetic resonance (MR). The contrast enhancement reduction on magnetic resonance imaging (MRI) of Mtb and THP1 cells showed proportional to the SPIO-MtbsAb nanoprobe concentration. After 30 min of intravenous SPIO-MtbsAb nanoprobe injection into Mtb-infected mice, the signal intensity of the granulomatous site was enhanced by 14-fold in the T2-weighted MR images compared with that in mice receiving PBS injection. The MtbsAb nanoprobes can be used as a novel modality for ETB detection.


Assuntos
Dextranos/síntese química , Nanopartículas de Magnetita/química , Tuberculose/diagnóstico , Animais , Anticorpos Antibacterianos/imunologia , Compostos Férricos , Humanos , Injeções Intravenosas , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Tamanho da Partícula , Células THP-1 , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/patologia
9.
J Nanobiotechnology ; 18(1): 6, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910856

RESUMO

BACKGROUND: Haptoglobin is an acute-phase protein used as predicting diagnostic biomarker both in humans (i.e., diabetes, ovarian cancer, some neurological and cardiovascular disorders) and in animals (e.g., bovine mastitis). The latter is a frequent disease of dairy industry with staggering economical losses upon decreased milk production and increased health care costs. Early stage diagnosis of the associated diseases or inflammation onset is almost impossible by conventional analytical manners. RESULTS: The present study demonstrates a simple, rapid, and cost-effective label-free chemiluminescence bioassay based on magnetite nanoparticles (MNPs) for sensitive detection of haptoglobin by employing the specific interaction of hemoglobin-modified MNPs. The resulting haptoglobin-hemoglobin complex inhibits the peroxidase-like activity of luminol/H2O2-hemoglobin-MNPs sensing scheme and reduces the chemiluminescence intensities correspondingly to the innate haptoglobin concentrations. Quantitative detection of bovine haptoglobin was obtained within the range of 1 pg mL-1 to 1 µg mL-1, while presenting 0.89 pg mL-1 limit of detection. Moreover, the influence of causative pathogenic bacteria (i.e., Streptococcus dysgalactiae and Escherichia coli) and somatic cell counts (depicting healthy, sub-clinical and clinical mastitis) on the emitted chemiluminescence radiation were established. The presented bioassay quantitative performances correspond with a standardized assay kit in differentiating dissimilar milk qualities. CONCLUSIONS: Overall, the main advantage of the presented sensing concept is the ability to detect haptoglobin, at clinically relevant concentrations within real milk samples for early bio-diagnostic detection of mastitis and hence adjusting the precise treatment, potentially initiating a positive influence on animals' individual health and hence on dairy farms economy.


Assuntos
Biomarcadores/análise , Haptoglobinas/análise , Medições Luminescentes , Nanopartículas de Magnetita/química , Animais , Bioensaio , Calibragem , Bovinos , Contagem de Células , Nanopartículas de Magnetita/ultraestrutura , Leite/microbiologia
10.
Nanotechnology ; 31(2): 025605, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31557732

RESUMO

In the present work, a fluorescent gold nanoclusters (GNCs)/superparamagnetic (Fe3O4/GNCs) nanoprobe was prepared via a facile approach for the selective detection and imaging of human leukemica cancer cells (HL-60). (γ-Mercaptopropyl)trimethoxysilane (MPS) was used as a stabilizer to prepare functionalized GNCs. The prepared GNCs@MPS was then self-assembly decorated on the surface of Fe3O4@SiO2 nanoparticles followed by poly(ethylene glycol) dimethacrylate (PGD) addition at room temperature to form Fe3O4/GNCs nanoprobe. Surface functionalization of the Fe3O4/GNCs with the thiol-modified KH1C12 aptamer was done through thiol-en click reaction between PGD and the thiol group of the aptamer. An extensive characterization of the Fe3O4/GNCs revealed strong red fluorescence (λ em = 627 nm), T 2-based contrast agent for MRI and excellent colloidal and photo stability in buffer medium. So, the aptamer-functionalized Fe3O4/GNCs nanoprobe (Fe3O4/GNCs/Aptamer) is capable to uptake and dual-image HL-60 cancer cells from a mixture. Furthermore, the MRI signal intensity of the pictures decreased linearly with an increase in the concentrations of the nanoprobe. It is also enable to detect cancer cells from a range of concentrations 10 up to 200 cells µL-1. The fluorescent/magnetic characteristics of the nanoprobe are of great significance for MRI-based and fluorescence imaging and collection of HL-60 cancer cells which implies potential help for the development of early diagnosis of highly malignant human leukemia.


Assuntos
Aptâmeros de Peptídeos/química , Separação Celular/métodos , Ouro/química , Nanopartículas de Magnetita/química , Fluorescência , Células HL-60 , Células Hep G2 , Humanos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura
11.
Int J Nanomedicine ; 14: 9647-9663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824157

RESUMO

Background: Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. Purpose: To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs. Methods: Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue. Results: In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated. Conclusion: These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Compostos Férricos/química , Hipertermia Induzida , Linfoma/terapia , Nanopartículas de Magnetita/química , Metotrexato/uso terapêutico , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Temperatura , Testes de Toxicidade Aguda
12.
Molecules ; 24(24)2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31861222

RESUMO

The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron-iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents while limited information on their engineering is available. Here we report the synthesis of 10 nm large Fe@FeOx nanoparticles, their coating with a 11 nm thick layer of dense silica and functionalization by 5 kDa PEG chains to improve their biocompatibility. The nanomaterials obtained have been characterized by a set of complementary techniques such as infra-red and nuclear magnetic resonance spectroscopies, transmission electron microscopy, dynamic light scattering and zetametry, and magnetometry. They display hydrodynamic diameters in the 100 nm range, zetapotential values around -30 mV, and magnetization values higher than the reference contrast agent RESOVIST®. They display no cytotoxicity against 1BR3G and HCT116 cell lines and no hemolytic activity against human red blood cells. Their nuclear magnetic relaxation dispersion (NMRD) profiles are typical for nanomaterials of this size and magnetization. They display high r2 relaxivity values and low r1 leading to enhanced r2/r1 ratios in comparison with RESOVIST®. All these data make them promising contrast agents to detect early stage tumors.


Assuntos
Dextranos/química , Compostos Férricos/química , Ferro/química , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Dióxido de Silício , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis , Humanos , Nanopartículas de Magnetita/ultraestrutura , Modelos Teóricos , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier
13.
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
14.
Int J Nanomedicine ; 14: 6661-6678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695362

RESUMO

Background: Cancer treatments are being continually developed. Increasingly more effective and better-targeted treatments are available. As treatment has developed, the outcomes have improved. Purpose: In this work, polyethylene glycol (PEG), layered double hydroxide (LDH) and 5-fluorouracil (5-FU) were used as a stabilizing agent, a carrier and an anticancer active agent, respectively. Characterization and methods: Magnetite nanoparticles (Fe3O4) coated with polyethylene glycol (PEG) and co-coated with 5-fluorouracil/Mg/Al- or Zn/Al-layered double hydroxide were synthesized by co-precipitation technique. Structural, magnetic properties, particle shape, particle size and drug loading percentage of the magnetic nanoparticles were investigated by XRD, TGA, FTIR, DLS, FESEM, TEM, VSM, UV-vis spectroscopy and HPLC techniques. Results: XRD, TGA and FTIR studies confirmed the formation of Fe3O4 phase and the presence of iron oxide nanoparticles, polyethylene glycol, LDH and the drug for all the synthesized samples. The size of the nanoparticles co-coated with Mg/Al-LDH is about 27 nm compared to 40 nm when they were co-coated with Zn/Al-LDH, with both showings near uniform spherical shape. The iron oxide nanoparticles retain their superparamagnetic property when they were coated with polyethylene glycol, polyethylene glycol co-coated with Mg/Al-LDH and polyethylene glycol co-coated with Zn/Al-LDH with magnetic saturation value of 56, 40 and 27 emu/g, respectively. The cytotoxicity study reveals that the anticancer nanodelivery system has better anticancer activity than the free drug, 5-FU against liver cancer HepG2 cells and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells. Conclusion: These are unique core-shell nanoparticles synthesized with the presence of multiple functionalities are hoped can be used as a multifunctional nanocarrier with the capability of targeted delivery using an external magnetic field and can also be exploited as hypothermia for cancer cells in addition to the chemotherapy property.


Assuntos
Fluoruracila/farmacologia , Hidróxidos/química , Fenômenos Magnéticos , Polietilenoglicóis/química , Nanomedicina Teranóstica , Células 3T3 , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Células Hep G2 , Humanos , Concentração Inibidora 50 , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
15.
Int J Nanomedicine ; 14: 8483-8497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695376

RESUMO

Introduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules. Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation. Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%. Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.


Assuntos
Aminas/química , Antibacterianos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Nanopartículas de Magnetita/química , Nanoconjugados/química , Proteínas/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Hemólise/efeitos dos fármacos , Humanos , Nanopartículas de Magnetita/ultraestrutura , Proteínas/química
16.
Chem Soc Rev ; 48(24): 5717-5751, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31720618

RESUMO

The detection of clinically relevant disease-specific biomolecules, including nucleic acids, circulating tumor cells, proteins, antibodies, and extracellular vesicles, has been indispensable to understand their functions in disease diagnosis and prognosis. Therefore, a biosensor for the robust, ultrasensitive, and selective detection of these low-abundant biomolecules in body fluids (blood, urine, and saliva) is emerging in current clinical research. In recent years, nanomaterials, especially superparamagnetic nanomaterials, have played essential roles in biosensing due to their intrinsic magnetic, electrochemical, and optical properties. However, engineered multicomponent magnetic nanoparticle-based current biosensors that offer the advantages of excellent stability in a complex biomatrix; easy and alterable biorecognition of ligands, antibodies, and receptor molecules; and unified point-of-care integration have yet to be achieved. This review introduces the recent advances in superparamagnetic nanostructures for electrochemical and optical biosensing for disease-specific biomarkers. This review emphasizes the synthesis, biofunctionalization, and intrinsic properties of nanomaterials essential for robust, ultrasensitive biosensing. With a particular emphasis on nanostructure-based electrochemical and optical detection of disease-specific biomarkers such as nucleic acids (DNA and RNA), proteins, autoantibodies, and cells, this review also chronicles the needs and challenges of nanoarchitecture-based detection. These summaries provide further insights for researchers to inspire their future work on the development of nanostructures for integrating into biosensing and devices for a broad field of applications in analytical sensing and in clinic.


Assuntos
Técnicas Biossensoriais/métodos , Nanopartículas de Magnetita/química , Animais , Anticorpos/análise , Biomarcadores/análise , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Desenho de Equipamento , Humanos , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia/métodos , Ácidos Nucleicos/análise , Proteínas/análise
17.
Int J Nanomedicine ; 14: 6721-6732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686805

RESUMO

Background: The early and accurate detection afforded by imaging techniques significantly reduces mortality in cancer patients. However, it is still a great challenge to achieve satisfactory performance in tumor diagnosis using any single-modality imaging method. Magnetic resonance imaging (MRI) has excellent soft tissue contrast and high spatial resolution, but it suffers from low sensitivity. Fluorescence imaging has high sensitivity, but it is limited by penetration depth. Thus, the combination of the two modes could result in synergistic benefits. Here, we design and characterize a novel dual-modality MR/near-infrared fluorescence imaging (MR/NIRFI) nanomicelle and test its imaging properties in mouse models of breast cancer. Methods: The nanomicelles were prepared by incorporating superparamagnetic iron oxide (SPIO) nanoparticles into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] micelles to which an NIRF dye and a tumor-targeted peptide (N3-Lys-bombesin, Bom) were conjugated. The nanomicelles were characterized for particle size, zeta potential and morphology. The transverse relaxivity, targeting specificity and imaging ability of the nanomicelles for MR/NIRFI were also examined. Results: The fabricated nanomicelles displayed a well-defined spherical morphology with a mean diameter of 145±56 nm and a high transverse relaxivity (493.9 mM-1·s-1, 3.0T). In MRI, the T2 signal reduction of tumors in the Bom-targeted group was 24.1±5.7% at 4 hrs postinjection, whereas only a 0.1±3.4% (P=0.003) decrease was observed in the nontargeted group. In NIRFI, the contrast increased gradually in the targeted group, and the tumor/muscle ratio increased from 3.7±0.3 at 1 hr to 4.7±0.1 at 2 hrs and to 6.4±0.2 at 4 hrs. No significant changes were observed in the nontargeted group at any time points. Conclusion: Considering all our results, we conclude that these novel MR/NIRFI dual-modality nanomicelles could be promising contrast agents for cancer diagnosis.


Assuntos
Bombesina/farmacologia , Bombesina/uso terapêutico , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Animais , Bombesina/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Fluorescência , Humanos , Nanopartículas de Magnetita/ultraestrutura , Neoplasias Mamárias Animais/tratamento farmacológico , Camundongos , Micelas , Imagem Óptica , Tamanho da Partícula
18.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652583

RESUMO

The present work reports the successful synthesis of biosynthesized iron oxide nanoparticles (Fe3O4-NPs) with the use of non-toxic leaf extract of Neem (Azadirachta indica) as a reducing and stabilizing agent. The successful synthesis was confirmed by infrared spectra analysis with strong peak observed between 400-600 cm-1 that corresponds to magnetite nanoparticles characteristics. X-ray diffraction (XRD) analysis revealed that iron oxide nanoparticles were of high purity with crystalline cubic structure phases in nature. Besides, the average size of magnetite nanoparticles was observed to be 9-12 nm with mostly irregular shapes using a transmission electron microscope (TEM) and was supported by field emission scanning electron microscope (FESEM). Energy dispersive X-ray analysis shown that the elements iron (Fe) and oxygen (O) were present with atomic percentages of 33.29% and 66.71%, respectively. From the vibrating sample magnetometer (VSM) analysis it was proven that the nanoparticles exhibited superparamagnetic properties with a magnetization value of 73 emu/g and the results showed superparamagnetic behavior at room temperature, suggesting potential applications for a magnetic targeting drug delivery system.


Assuntos
Azadirachta/química , Compostos Férricos/química , Nanopartículas de Magnetita/química , Extratos Vegetais/química , Sistemas de Liberação de Medicamentos , Compostos Férricos/metabolismo , Magnetismo , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Folhas de Planta/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Int J Nanomedicine ; 14: 8105-8119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632021

RESUMO

Background: Super-paramagnetic iron oxide nanoparticles (SPIONs) are widely used metal nanoparticles for various applications for its magnetic property and biocompatibility. In recent years, pollution of our environment especially with heavy metals in waterbodies has become a major threat and has left us very minimal sources of freshwater to drink. SPIONs or surface modified SPIONs can be used to remove these heavy metals. Methods: SPIONs were synthesized by co-precipitation method and further coated with a biopolymer, chitosan. Chromium solution was treated with the synthesized SPIONs to study the efficiency of chromium removal by surface adsorption. Later, the adsorption was analysed by direct and indirect analysis methods using UV-VIS spectrophotometry and isotherm studies. Results: Stable chitosan-coated SPIONs were synthesized and they adsorbed chromium better than the uncoated SPIONs, where it was adsorbing up to 100 ppm. Adsorption was found to be increasing with decrease in pH. Conclusion: The surface-modified SPIONs expressed cumulative adsorption action. Even after the adsorption studies, chitosan-coated SPIONs were possessing magnetic property. Thus, the surface-modified SPIONs can become an ideal nanotechnology tool to remove the chromium from groundwater.


Assuntos
Cromo/isolamento & purificação , Compostos Férricos/química , Nanopartículas de Magnetita/química , Nanotecnologia/métodos , Adsorção , Concentração de Íons de Hidrogênio , Nanopartículas de Magnetita/ultraestrutura , Nanopartículas/química , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Propriedades de Superfície , Temperatura , Fatores de Tempo , Difração de Raios X
20.
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
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