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1.
In this study, a stable carboxylated luteolin (CL)-functionalized superparamagnetic iron oxide nanoparticle (SPION) as a potential drug carrier for in vitro analysis of L929 (mouse fibroblast), U87 (glioblastoma (brain cancer)), MCF-7 (breast cancer), HeLa (cervix cancer), and A549 (human lung cancer) cell lines has been synthesized. Thermal decomposition and Stöber methods were used to prepare 3-aminopropyl triethoxysilane-capped SPIONs respectively. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and CL were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method respectively. Internalization of CL-functionalized SPION and the release of luteolin from it has been studied using Prussian blue staining and spectrophotometry respectively. The cytotoxicity of CL-functionalized SPION on cell lines was tested by MTT assay. Internalization of product by HeLa, MCF-7, and U87 was higher than A549 and L929 cells. It was observed that luteolin release increased in an acidic environment (pH 5.4). A newly synthesized SPION-FA-PEG in all concentrations (except 500 μg/mL) did not show notable toxicity against L929, U87, MCF-7, HeLa, and A549. However, the product in all used concentrations decreased cell viability at the 24th and 48th hours. This study confirmed that the product has a potential to be used as an anti-cancer CL-functionalized SPION for targeted drug delivery.  相似文献   

2.
There have been a number of studies which deal with either toxic or non-toxic nature of superparamagnetic iron oxide nanoparticles (SPIONs); however, there is no clear cut information about their exact behavior and the reasons for its dual action. The objective of the present study was to investigate the SPIONs having similar oxidation states, but varying surface ligands and their role in terms of protecting the iron-mediated toxic responses. The four different SPIONs includes: (i) SPIONs containing oleic acid (SPIONs-1), (ii) SPIONs without any surface ligand (SPIONs-2), (iii) SPIONs containing cysteamine ligand (SPIONs-3), and (iv) SPIONs having both of oleic acid and cysteamine ligand. The particle size, surface functionality, and electronic oxidation states were confirmed by the HRTEM, FT-IR, and XPS analysis, respectively. On in vitro testing of all four SPIONs with H9c2 cardiomyocyte cell line, the SPIONs-2 without any surface ligand found to exhibit significant decrease in the viability of cells at a concentration of 200 μg mL?1 for 16-h exposure period. Further investigation of toxicity mechanism resulted in the fact that the SPIONs-2 involved in the formation of ROS due to the role played by the more electron deficient Fe3+ form of iron, there by decreased the glutathione release, increased DNA cleavage, and disrupted the mitochondrial transmembrane potential. However, the presence of unsaturation and/or thiol group (–SH) containing ligands on other SPIONs protected the cardiac cells from undergoing ROS-induced oxidative stress. Further, the results of the study confirming the importance of having unsaturated double bonds and/or –SH group possessing ligands onto the surface of SPIONs by means of protecting the cells from the influence of electron deficient Fe3+ state of iron.  相似文献   

3.
This paper shows that superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH–SPIONs), can be used to target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging of breast cancer xenografts. A combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used in our experiments, to investigate the specific accumulation of the functionalized superparamagnetic iron oxide nanoparticles (SPIONs) in cancer cells. The contrast enhancement of conventional T2 images obtained from the tumor tissue and of breast cancer xenograft bearing mice is shown to be much greater than that in saline controls, when the tissues were injected with LHRH–SPIONs. Magnetic anisotropy multi-CRAZED images of tissues extracted from mice injected with SPIONs were also found to have enhanced MRI contrast in breast cancer xenografts and metastases in the lungs.  相似文献   

4.
The potential of superparamagnetic iron oxide nanoparticles (SPIONs) in various biomedical applications, including magnetic resonance imaging (MRI), sensing, and drug delivery, requires that their surface be derivatized to be hydrophilic and biocompatible. We report here the design and synthesis of a compact and water-soluble zwitterionic dopamine sulfonate (ZDS) ligand with strong binding affinity to SPIONs. After ligand exchange, the ZDS-coated SPIONs exhibit small hydrodynamic diameters, and stability with respect to time, pH, and salinity. Furthermore, small ZDS coated SPIONs were found to have a reduced nonspecific affinity (compared to negatively charged SPIONs) toward serum proteins; streptavidin/dye functionalized SPIONs were bioactive and thus specifically targeted biotin receptors.  相似文献   

5.
We report here the development of stable aqueous suspensions of biocompatible superparamagnetic iron oxide nanoparticles (SPIONs). These so-called ferrofluids are useful in a large spectrum of modern biomedical applications, including novel diagnostic tools and targeted therapeutics. In order to provide prolonged circulation times for the nanoparticles in?vivo, the initial iron oxide nanoparticles were coated with a biocompatible polymer poly(ethylene glycol) (PEG). To permit covalent bonding of PEG to the SPION surface, the latter was functionalized with a coupling agent, 3-aminopropyltrimethoxysilane (APS). This novel method of SPION PEGylation has been reproduced in numerous independent preparations. At each preparation step, particular attention was paid to determine the physico-chemical characteristics of the samples using a number of analytical techniques such as atomic absorption, Fourier transform infrared (FT-IR) spectroscopy and Raman spectroscopy, transmission electron microscopy (TEM), photon correlation spectroscopy (PCS, used for hydrodynamic diameter and zeta potential measurements) and magnetization measurements. The results confirm that aqueous suspensions of PEGylated SPIONs are stabilized by steric hindrance over a wide pH range between pH 4 and 10. Furthermore, the fact that the nanoparticle surface is nearly neutral is in agreement with immunological stealthiness expected for the future biomedical applications in?vivo.  相似文献   

6.
Highly monodisperse superparamagnetic iron oxide nanoparticles (SPIONs, 7.5 nm gamma- F2O3) were synthesized by thermal decomposition of iron pentacarbonyl and consecutive aeration in organic medium. By treating with a small amount of iron pentacarbonyl, Fe-rich surface has been formed on SPION. Water-dispersible SPIONs (SPION-MPA) were prepared by Fe-S covalent conjugation between Fe-rich SPION and mercaptopropionic acid (MPA) and then, transformed to SPION-MPA-dextran composite by physical adsorption of biocompatible polymer dextran. The hydrodynamic diameter of SPION-MPA-dextran was in the range of 225~237 nm in water. MR contrast and spin-spin relaxation intensity of our SPION-MPA-dextran were similar to those of the commercial products, Ferridex and Resovist.  相似文献   

7.
Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. Membrane‐bound 70 kDa heat shock protein (mHsp70) is ubiquitously expressed on the cell membrane of various tumor types but not normal cells and therefore provides a tumor‐specific target. The serine protease granzyme B (GrB) that is produced as an effector molecule by activated T and NK cells has been shown to specifically target mHsp70 on tumor cells. Following binding to Hsp70, GrB is rapidly internalized into tumor cells. Herein, it is demonstrated that GrB functionalized SPIONs act as a contrast enhancement agent for magnetic resonance imaging and induce specific tumor cell apoptosis. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting are found to further enhance the therapeutic efficacy of GrB‐SPIONs in different tumor mouse models.  相似文献   

8.
In modern medicine, major attention has been paid to superparamagnetic iron oxide nanoparticles (SPIONs). Recent studies have shown the antibacterial properties of SPIONs against some Gram‐positive and Gram‐negative bacterial strains. These nanoparticles (NPs) can bind to bacterial membranes via hydrophobic or electrostatic interactions and pass through cell barriers. In this study, the authors evaluated the antibacterial activity of magnetic NPs in comparison with ferrous and ferric ions. The level of reactive oxygen species (ROS) in the treated Staphylococcus aureus and Escherichia coli bacteria were directly measured by fluorometric detection. The results showed that iron ions and SPIONs had significant dependent antimicrobial activities. SPIONs showed greater inhibitory effects than ferrous and ferric ions against the growth of treated bacterial strains under anaerobic conditions, while in aerobic conditions, ferrous showed the strongest antibacterial activity. In anaerobic conditions, they observed the greatest ROS formation and lowest minimum inhibitory concentration in the SPION‐treated group in comparison with the other groups. It seems that the release of iron ions from SPIONs and subsequent activation of ROS pathway are the main antibacterial mechanisms of action. Nevertheless, the greater antibacterial effect of SPIONs in anaerobic conditions represents other mechanisms involved in the antibacterial activity of these NPsInspec keywords: nanomagnetics, antibacterial activity, hydrophobicity, nanoparticles, superparamagnetism, biomedical materials, iron compounds, membranes, nanobiotechnologyOther keywords: ferrous ions, anaerobic conditions, superparamagnetic iron oxide nanoparticles, antibacterial properties, bacterial membranes, electrostatic interactions, bacterial strains, aerobic conditions, SPION‐treated group, antibacterial effect, cell barriers, 2′,7′‐dichlorodihydrofluorescein diacetate, reactive oxygen species, fluorometric detection, Staphylococcus aureus, Escherichia coli  相似文献   

9.
In this present study, a facile synthetic route was developed to prepare super-paramagnetic Fe3O4 MNPs directly via a one-pot approach. In this synthesis, only one iron containing compound and instead of high-boiling-point solvents, water-soluble tetraethylene glycol (TEG) was used as both the solvent and surfactant to control the particle growth and to prevent the aggregation of particles. Crystallite, particle, and magnetic core size are in good agreement with each other. The VSM measurement shows the superparamagnetic property of the product. The existence of TEG layer on the surface of the Fe3O4 nanoparticles was confirmed by Fourier transform infrared spectroscopy and thermal gravimetric analysis. The monodisperse morphology of the product was presented via TEM analysis. Due to the monodisperse morphology, superparamagnetic property, and small particle size, the product may have a potential application in biomedical research field.  相似文献   

10.
In this work, we present a short summary of the synthesis and characterization of superparamagnetic iron oxide nanoparticles and their behavior in vitro and in vivo. Therefore, we have used various characterization techniques to deduce the physical particle size as well as magnetic properties. It is shown that the particle properties were significantly improved by a thermochemical treatment and dialysis, obtaining weakly interacting particles with a clear blocking temperature. We also present the interaction of polyvinyl alcohol and vinyl alcohol/vinyl amine copolymer-coated SPIONs with HELA cells. It is shown that the uptake increased significantly in the presence of a magnetic field and that surface functional groups had an impact on particle uptake and metabolic activity. Furthermore, the influences of the varied parameters (polymer type and therefore surface charge, cell medium, and serum) on the agglomeration rate and the cell uptake are presented and discussed. Finally, we briefly describe the intraarticular application of SPIONs in sheep, their uptake by synovial membrane, and their systemic distribution and elimination.  相似文献   

11.
In this study, magnetic nanoparticles (MNPs) coated with L-aspartic acid (F-Asp NPs) were synthesized through a co-precipitation method and conjugated with paclitaxel (PTX) (F-Asp-PTX NPs) by esterification reaction between the carboxylic acid end groups on MNPs surface and the hydroxyl groups of the PTX and studied its cytotoxic effect in vitro. The successful conjugating of PTX onto the nanoparticles (NPs) was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. The results showed that the average size was 46.11?±?7.8 (mean?±?SD (n?=?25)) nm. The cytotoxicity of void of PTX and F-Asp-PTX NPs were compared to each other by MTT assay of the treated MCF-7 cell line. The F-Asp-PTX NPs showed pH-dependent drug release behavior. These studies specify that F-Asp-PTX NPs have a very remarkable anticancer effect, for breast cancer cell line.  相似文献   

12.
Super‐paramagnetic iron oxide nanoparticles (SPIONs) are recognized as powerful biocompatible materials for use in various biomedical applications, such as drug delivery, magnetic‐resonance imaging, cell/protein separation, hyperthermia and transfection. This study investigates the impact of high concentrations of SPIONs on cytotoxicity and cell‐cycle effects. The interactions of surface‐saturated (via interactions with cell medium) bare SPIONs and those coated with poly(vinyl alcohol) (PVA) with adhesive mouse fibroblast cells (L929) are investigated using an MTT assay. The two SPION formulations are synthesized using a co‐precipitation method. The bare and coated magnetic nanoparticles with passivated surfaces both result in changes in cell morphology, possibly due to clustering through their magnetostatic effect. At concentrations ranging up to 80 × 10?3 M , cells exposed to the PVA‐coated nanoparticles demonstrate high cell viability without necrosis and apoptosis. In contrast, significant apoptosis is observed in cells exposed to bare SPIONs at a concentration of 80 × 10?3 M . Nanoparticle exposure (20–80 × 10?3 M ) leads to variations in both apoptosis and cell cycle, possibly due to irreversible DNA damage and repair of oxidative DNA lesions, respectively. Additionally, the formation of vacuoles within the cells and granular cells indicates autophagy cell death rather than either apoptosis or necrosis.  相似文献   

13.
Stable superparamagnetic magnetite (Fe3O4) nanoparticles were synthesized via co-precipitation in the presence of poly(methacrylic acid) (PMAA) in aqueous solution. The polymer coated Fe3O4 nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis, and vibrating sample magnetometry (VSM) techniques. These measurements reveal the presence of magnetite nanoparticles with a size of approximately 8 nm inside the PMAA matrix. The magnetization value of these superparamagnetic nanoparticles at room temperarure and 7 T was measured as about 40 emu/g. PMAA-coated Fe3O4 nanoparticles were further assembled with Ni-chelate through a reaction between a primary amine-bearing NTA (nitrilotriacetic acid) ligand and carboxy-functional groups of PMAA. NTA-PMAA-coated magnetite nanoparticles were then loaded with nickel ions and characterized using FTIR. The average amount of binded Ni on the surface of the NTA-modified PMAA coated Fe3O4 was calculated as 1.65 +/- 0.3 x 10(-6) mol nickel(II) ions per g of the magnetic particles from the inductively coupled plasma optical emission spectroscopy (ICP-OES) measurements.  相似文献   

14.
Micro/nanobubbles for use as ultrasound contrast agents have been fabricated with different shell materials.When various biomedical nanoparticles have been embedded in the shells of bubbles,the composite structures have shown promising applications in multi-modal imaging,drug/gene delivery,and biomedical sensing.In this study,we developed a new gas-liquid interface self-assembly method to prepare magnetic nanobubbles embedded with superparamagnetic iron oxide nanoparticles(SPIONs).The diameter of the generated assembled nanobubbles was 227.40±87.21 nm with a good polydispersity index(PDI)of 0.29.Under the condition of 150 compression cycles,the nanobubble concentration could reach about 6.12×109/mL.Transmission electron microscopy(TEM)and scanning electronic microscopy(SEM)demonstrated that the assembled nanobubbles had a hollow gas core with SPIONs adsorbed on the surface.Ultrasound(US)imaging and magnetic resonance imaging(MRI)experiments indicated that the assembled magnetic nanobubbles exhibited good US and MR contrast capabilities.Moreover,the assembled magnetic nanobubbles were used to label neural stem cells under ultrasound exposure.After 40 s US exposure,the magnetic nanobubbles could be delivered into cells with 2.80 pg Fe per cell,which could be observed in the intracellular endosome by TEM.Compared with common incubation methods,the ultrasound exposure method did not introduce the potential cytotoxicity of transfection reagents and the efficiency was about twice as high as the efficiency of incubation.Therefore,the assembled magnetic nanobubbles prepared through the pressure-driven gas-liquid interface assembly approach could be a potential US/MRI dual model imaging nanocarrier for regenerative applications.  相似文献   

15.
This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy‐dispersive X‐ray spectroscopy, and scanning electron microscopy. Then, alginate‐SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4°C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate‐SPION‐sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.Inspec keywords: drug delivery systems, drugs, nanofabrication, magnetic particles, iron compounds, scanning electron microscopy, hyperthermia, biomedical materials, encapsulation, nanoparticles, light scattering, nanomagnetics, cellular biophysics, toxicology, cancer, nanomedicine, superparamagnetism, nanocomposites, magnetometry, paramagnetic resonance, X‐ray chemical analysisOther keywords: sorafenib loaded alginate microspheres, hepatocellular carcinoma treatment, sorafenib loaded magnetic microspheres, superparamagnetic iron oxide nanoparticles, dynamic light scattering, energy‐dispersive X‐ray spectroscopy, scanning electron microscopy, electron spin resonance spectrometer, vibrating sample magnetometer, hyperthermia treatment, drug release, alginate‐SPION‐sorafenib microspheres, antineoplastic agent, cytotoxicity tests, cancerous cells, time 8.0 hour, Fe3 O4   相似文献   

16.
Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.  相似文献   

17.
Hu F  Jia Q  Li Y  Gao M 《Nanotechnology》2011,22(24):245604
The development of new types of high-performance nanoparticulate MR contrast agents with either positive (T(1)) or dual-contrast (both positive and negative, T(1) + T(2)) ability is of great importance. Here we report a facile synthesis of ultrasmall PEGylated iron oxide nanoparticles for dual-contrast T(1)- and T(2)-weighted MRI. The produced superparamagnetic iron oxide nanoparticles (SPIONs) are of high crystallinity and size uniformity with an average diameter of 5.4 nm, and can be individually dispersed in the physiological buffer with high stability. The SPIONs reveal an impressive saturation magnetization of 94 emu g(-1) Fe(3)O(4), the highest r(1) of 19.7 mM(-1) s(-1) and the lowest r(2)/r(1) ratio of 2.0 at 1.5 T reported so far for PEGylated iron oxide nanoparticles. T(1)- and T(2)-weighted MR images showed that the SPIONs could not only improve surrounding water proton signals in the T(1)-weighted image, but induce significant signal reduction in the T(2)-weighted image. The good contrast effect of the SPIONs as T(1) + T(2) dual-contrast agents might be due to its high magnetization, optimal nanoparticle size for T(1) + T(2) dual-contrast agents, high size monodispersity and excellent colloidal stability. In vitro cell experiments showed that the SPIONs have little effect on HeLa cell viability.  相似文献   

18.
Antigen delivery using nanoparticles becomes useful and novel strategy to develop immunotherapeutic approaches against cancer. In the current study, we examined the feasibility of SPIONs-mediated delivery of antigenic peptides to local tumor for application to cancer immunotherapy. SPIONs carrying murine melanoma antigens, hgp100(25-33) were prepared and used to test its efficacy in mouse model. Efficient uptake of peptide-conjugated SPIONs by murine dendritic cells (DCs) was shown, using NP labeled with the fluorescent dye Furthermore, potential targeting effect of SPIONs carrying tumor antigenic peptide was verified in vitro and in vivo. Our results demonstrate the feasibility of SPIONs-mediated antigen delivery for cancer immunotherapy and highlight the clinical potential of SPIONs for future cancer treatment with high efficacy.  相似文献   

19.
In this study, fluorescent dendro-nized magnetic nanoparticles (FDMNPs) with their unique pH sensitive nature were synthesized for biomedical applications. First, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared by coprecipitation of F e +2 and F e +3 with N H 4 O H, and then modified by amino silane. Polyamidoamine (PAMAM) dendrimer were coated on the SPION-APTS surface using Michel addition method and grew from generation 0.5 to 3. In the final step of synthesis, the reaction between isoslulfosyanic groups of fluorescein isothiocyanate (FITC) and amine terminal groups of DMNPs was lead to the formation of magnetic fluorescent nanocomposites. The FDMNPs were studied using Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-visible spectroscopy, fluorescence spectroscopy, vibrating-sample magnetometery (VSM) ), zeta potential ,and Dynamic Light Scattering (DLS). The size of SPIONs and FDMNPs were about 10 nm and 14 nm, respectively. The possibility of conjugating a large number of fluorescein isothiocyanate (FITC) molecules on the SPIONs together with high amount of magnetization saturation ,Ms (52 emu/g in our case) and other unique characteristics have nominated FDMNPs as a suitable candidate for biomedical applications.  相似文献   

20.
Nano-/microplastics (NP) is a human-made emerging contaminant with worldwide occurrence. The small size (below one micrometer), the different chemical nature and the persistence make NP to potential hazards with suspect probability of tissue penetration and inflammation or as accumulator for toxins. A strategy to stop the spill of novel NP is the remediation from waste water or rivers as prominent distributors. We have developed core–shell superparamagnetic iron oxide nanoparticles (SPIONs) that attract NP and glue them to larger agglomerates which then can be removed from water by applying an external magnetic field. The shell molecules provide two interaction motifs towards NP. The tuned surface potential of the functionalized SPIONs attract complementary charged NP efficiently and the n-alkyl chain is dedicated to preferential interaction towards organic NP rather than inorganic particles. Structural analytics and molecular dynamics simulation support the proposed concept. Systematic remediation experiments with different NP (chemical structures, sizes and mixtures), from different waters – including river water – and with different SPION core materials indicate a universal validity of the concept, with best remediation performance for mixed NP. We suggest a method for broadband remediation of various NP with simple materials and processes, which both have the potential to be up-scaled.  相似文献   

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