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1.
This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T2, and the magnetic resonance transverse relaxation rate (ΔR2) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T2 signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis.  相似文献   

2.
The purpose of this study was to design chitosan microspheres (MS) loaded with superparamagnetic iron oxide nanoparticles (SPIO) suitable for anti-cancer embolotherapy detectable by MRI. Deformable chitosan MS loaded with varying SPIO concentrations (SPIO-chitosan MS) were prepared by ionotropic gelation and a porogenic technique using polyethylene glycol, followed by genipin crosslinking. Adding SPIO nanoparticles to chitosan MS did not significantly affect the chitosan MS morphology. An in vitro phantom study led to selecting SPIO-chitosan MS prepared with 1.0mM SPIO for an in vivo MR traceability study. SPIO-chitosan MS could be identified following embolization in the renal artery by MRI at 18weeks. Histological and pathological evidence also showed that SPIO-chitosan MS blocked and remained in the target vessels. Therefore, deformable SPIO-chitosan MS is MR-detectable embolic material with a possible application for anti-cancer embolotherapy.  相似文献   

3.
Magnetic iron oxide (IO) nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI), which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.  相似文献   

4.
Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents for use in magnetic resonance imaging (MRI) are currently undergoing clinical evaluation. However, the images observed and the kinetic profiles obtained differ from one agent to another. In this study, BD IX rats received an intravenous penis injection of the USPIO contrast agents AMI-HS and AMI-227. A cytologic study of the liver was performed, and the data obtained were compared with those of MRI. Images acquired in light microscopy, transmission electron microscopy, microanalysis and electron diffraction provided data on the cell categories involved in the processing of these contrast agents, the importance and modalities of each category relative to this processing, and the modalities of agent elimination. AMI-HS was rapidly removed from the bloodstream by Kupffer's cells and hepatocytes and then eliminated through bile ducts. AMI-227 remained much longer in the blood compartment since it was processed very slowly by endothelial and Kuppfer's cells in the near absence of hepatocytic participation and thus of elimination by the bile ducts. These results allowed us to base our interpretation of MRI sequences on cytologic observations.  相似文献   

5.
Iron oxide nanoparticles (IONPs) are broadly examined nanomaterials for their promising engagement of the progressive in biomedical application, for intense selective drug delivery and multimodal imaging. IONPs are commonly less price, and enhanced biocompatibility can be effectively functionalized with a broad range of functioning ligand, and have established to be active in improving clinical diagnostics tools and magnetic resonance imaging contrast agents. Consequently, IONPs could be used as a promising magnetic resonance imaging contrast. In this context, we have established an IONPs based framework for the multimodal in vitro imaging approach of gastric cancer cell lines that fast high level of glypican-3 protein (GLY-3) on the superficial. In this regards, a new GLY-3 peptide targeting model established and fabricated to IONPs. The aqueous property, biocompatibility profile and physical-chemical properties of the functionalized IONPs were characterised with various spectroscopical methods. The viability of the gastric SGC-7901 cells was examined by MTT assay. Further, the viability of the cells was evidenced through fluorescence staining methods. The binding ability and cellular uptake properties of naked IONPs and functionalized IONPs (GPC3@IONPs) were examined via laser scanning confocal microscopy (CLSM) in GLY-3 positive gastric cells (SGC-7901 cells). The obtained outcomes displayed that the GLY-3 functionalized IONPs remarkably improved the magnetic resonance imaging contrasts and were actively assured and occupied up by gastric cell lines without damaging the non-cancerous cells.  相似文献   

6.
In this report, we present a breast imaging technique combining high‐resolution near‐infrared (NIR) light induced photoacoustic tomography (PAT) with NIR dye‐labeled amino‐terminal fragments of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (NIR830‐ATF‐IONP) for breast cancer imaging using an orthotopic mouse mammary tumor model. We show that accumulation of the targeted nanoparticles in the tumor led to photoacoustic contrast enhancement due to the high absorption of iron oxide nanoparticles (IONP). NIR fluorescence images were used to validate specific delivery of NIR830‐ATF‐IONP to mouse mammary tumors. We found that systemic delivery of the targeted IONP produced 4‐ and 10‐fold enhancement in photoacoustic signals in the tumor, compared to the tumor of the mice that received non‐targeted IONP or control mice. The use of targeted nanoparticles allowed imaging of tumors located as deep as 3.1 cm beneath the normal tissues. Our study indicates the potential of the combination of photoacoustic tomography and receptor‐targeted NIR830‐ATF‐IONP as a clinical tool that can provide improved specificity and sensitivity for breast cancer detection. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)  相似文献   

7.
An accurate definition of clinical target volume (CTV) is essential for the application of radiotherapy in nasopharyngeal carcinoma (NPC) treatment. A novel epidermal growth factor receptor (EGFR)-targeting contrast agent (C225-USPIO) was designed by conjugating ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225), to non-invasively define the CTV of tumor. The immunobinding activity of C225-USPIO to NPC cell line CNE1 was confirmed by flow cytometry and immunofluorescence. The time-dependent accumulation of C225-USPIO in CNE1 cells was evaluated using Prussian blue staining. Targeted internalization and subcellular localization of C225-USPIO was confirmed by transmission electron microscope. The results indicated that C225-USPIO specifically bound to EGFR on the surface of CNE1 cells and was taken up into the cell. The uptake of C225-USPIO by CNE1 cells increased significantly with time, when compared with human IgG-USPIO. In addition, 4.7 T magnetic resonance imaging (MRI) revealed that C225-USPIO had a capacity to accumulate in the CNE1 cells, with a resultant marked decrease in MRI T2-weighted signal intensity over time. These findings imply that C225-USPIO has the potential as an MRI contrast agent and can be employed to non-invasively detect early-stage NPC with EGFR overexpression. This provides sufficient theoretical basis for commencing in vivo experiments with the compound.  相似文献   

8.
Yuk SH  Oh KS  Cho SH  Lee BS  Kim SY  Kwak BK  Kim K  Kwon IC 《Biomacromolecules》2011,12(6):2335-2343
We described the preparation of the glycol chitosan/heparin immobilized iron oxide nanoparticles (composite NPs) as a magnetic resonance imaging agent with a tumor-targeting characteristic. The iron oxide nanoseeds used clinically as a magnetic resonance imaging agent were immobilized into the glycol chitosan/heparin network to form the composite NPs. To induce the ionic interaction between the iron oxide nanoseeds and glycol chitosan, gold was deposited on the surface of iron oxide nanoseeds. After the immobilization of gold-deposited iron oxide NPs into the glycol chitosan network, the NPs were stabilized with heparin based on the ionic interaction between cationic glycol chitosan and anionic heparin. FE-SEM (field emission-scanning electron microscopy) and a particle size analyzer were used to observe the formation of the stabilized composite NPs, and a Jobin-Yvon Ultima-C inductively coupled plasma-atomic emission spectrometer (ICP-AES) was used to measure the contents (%) of formed iron oxide nanoseeds as a function of reaction temperature and formed gold deposited on the iron oxide nanoparticles. We also evaluated the time-dependent excretion profile, in vivo biodistribution, circulation time, and tumor-targeting ability of the composite NPs using a noninvasive NIR fluorescence imaging technology. To observe the MRI contrast characteristic, the composite NPs were injected into the tail veins of tumor-bearing mice to demonstrate their selective tumoral distribution. The MR images were collected with conventional T(2)-weighted spin echo acquisition parameters.  相似文献   

9.
The purpose of this study was to determine the cellular distribution and degradation in rat liver following intravenous injection of superparamagnetic iron oxide nanoparticles used for magnetic resonance imaging (NC100150 Injection). Relaxometric and spectrophotometric methods were used to determine the concentration of the iron oxide nanoparticles and their degradation products in isolated rat liver parenchymal, endothelial and Kupffer cell fractions. An isolated cell phantom was also constructed to quantify the effect of the degradation products on the loss of MR signal in terms of decreased transverse relaxation times, T2*. The results of this study show that iron oxide nanoparticles found in the NC100150 Injection were taken up and distributed equally in both liver endothelial and Kupffer cells following a single 5 mg Fe/kg body wt. bolus injection in rats. Whereas endothelial and Kupffer cells exhibited similar rates of uptake and degradation, liver parenchymal cells did not take up the NC100150 Injection iron oxide particles. Light-microscopy methods did, however, indicate an increased iron load, presumably as ferritin/hemosiderin, within the hepatocytes 24 h post injection. The study also confirmed that compartmentalisation of ferritin/hemosiderin may cause a significant decrease in the MRI signal intensity of the liver. In conclusion, the combined results of this study imply that the prolonged presence of breakdown product in the liver may cause a prolonged imaging effect (in terms of signal loss) for a time period that significantly exceeds the half-life of NC100150 Injection iron oxide nanoparticles in liver.  相似文献   

10.
During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug.  相似文献   

11.
Nanomedicine nowadays offers novel solutions in cancer therapy by introducing multimodal treatments in one single formulation. In addition, nanoparticles act as nanocarriers changing the solubility, biodistribution and efficiency of the therapeutic molecules, thus generating more efficient treatments and reducing their side effects. To apply these novel therapeutic approaches, efforts are focused on the multi-functionalization of the nanoparticles and will open up new avenues to advanced combinational therapies. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with unmet medical needs. Abundant expression of the anti-phagocytosis signal CD47 has also been observed on pancreatic cancer cells, in particular a subset of cancer stem cells (CSCs) responsible for resistance to standard therapy and metastatic potential. CD47 receptor is found on pancreatic cancer and highly expressed on CSCs, but not on normal pancreas. Inhibiting CD47 using monoclonal antibodies has been shown as an effective strategy to treat PDAC in vivo. However, CD47 inhibition effectively slowed tumor growth only in combination with Gemcitabine or Abraxane. In this work, we present the generation of multifunctionalized iron oxide magnetic nanoparticles (MNPs) that include the anti-CD47 antibody and the chemotherapeutic drug Gemcitabine in a single formulation. We demonstrate the in vitro efficacy of the formulation against CD47-positive pancreatic cancer cells. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.  相似文献   

12.
We investigated the potential of antibody-vectorialized superparamagnetic iron oxide (SPIO) particles as cellular specific magnetic resonance contrast agents to image lymphocyte populations within the central nervous system (CNS), with the final goal of obtaining a reliable tool for noninvasively detecting and tracking specific cellular populations in vivo. We used superparamagnetic particles bound to a monoclonal antibody. The particle is the contrast agent, by means of its T?* relaxation properties; the antibody is the targeting vector, responsible for homing the particle to target a surface antigen. To investigate the efficiency of particle vectorialization by these antibodies, we compared two types of antibody-vectorialized CD3-specific particles in vivo. We successfully employed vectorialized SPIO particles to image B220? cells in a murine model of B-cell lymphoma. Likewise, we were able to identify CD3? infiltrates in a murine model of multiple sclerosis. The specificity of the technique was confirmed by immunohistochemistry and electron microscopy of corresponding sections. Our findings suggest that indirect binding of the antibody to a streptavidinated particle allows for enhanced particle vectorialization compared to covalent binding of the antibody to the particle.  相似文献   

13.

Objective

To investigate the effects of ultrasmall superparamagnetic iron oxide (USPIO) labeling on the maturity or immune tolerance of immature dendritic cells (imDCs) as the success of immunotherapy with immature dendritic cells is highly dependent on immune tolerance.

Results

The feasibility of tracking implanted USPIO-labeled imDCs in vivo by magnetic resonance imaging (MRI) was explored. The effects of USPIO labeling on the immune tolerance of imDCs was examined. USPIO when higher than 200 μg/ml caused considerable damage to imDCs, induced imDC maturation, and impacted the immune tolerance of imDCs. USPIO labeling caused a dose-dependent increase in autophagosome formation in imDCs, and autophagy inhibitors prevented the maturation of imDCs while stimulating their immune tolerance.

Conclusions

We speculate that high concentrations of USPIO can be used to induce imDC maturation, and that this process is likely mediated through an autophagy-related pathway.
  相似文献   

14.
Superparamagnetic iron oxide nanoparticles (SPIONs) are excellent MR contrast agents when coated with biocompatible polymers such as hydrophilic synthetic polymers, proteins, polysaccharides, and lipids, which improve their stability and biocompatibility and reduce their aggregation. Various biocompatible materials, coated or conjugated with targeting moieties such as galactose, mannose, folic acid, antibodies and RGD, have been applied to SPION surfaces to provide tissue specificity to hepatocytes, macrophages, and tumor regions in order to reduce non-specific uptake and improve biocompatibility. This review discusses the recent progress in the development of biocompatible and hydrophilic polymers for improving stability of SPIONs and describes the carbohydrates based biocompatible materials that are providing SPIONs with cell/tissue specificity as ligands.  相似文献   

15.
C Huang  KG Neoh  L Xu  ET Kang  E Chiong 《Biomacromolecules》2012,13(8):2513-2520
Amphiphilic poly(ε-caprolactone)-b-poly(propargyl methacrylate-click-mercaptosuccinic acid-co-poly(ethylene glycol) methyl ether methacrylate) (PCL-b-P(PMA-click-MSA-co-PEGMA)) were synthesized by a combination of ring-opening polymerization, reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiol-yne "click" reaction. The hydrophobic PCL core can be used to load superparamagnetic iron oxide nanoparticles (SPIONs), while the pendant dicarboxylic groups in the hydrophilic shell are used to coordinate cisplatin. These SPIONs-loaded, cisplatin-conjugated polymeric nanoparticles (Pt-Fe-PNs) are superparamagnetic at room temperature and are mucoadhesive. Release of cisplatin from Pt-Fe-PNs in artificial urine at 37 °C was characterized by an initial burst release with a release of ~30% of the cisplatin in the first 4 h followed by a slow sustained release over 4 days. The cisplatin release can be further enhanced by increasing the temperature. These Pt-Fe-PNs can effectively induce cytotoxicity against UMUC3 bladder cancer cells with IC(50) of 32.3 μM. These results indicate that Pt-Fe-PNs is potentially a promising cisplatin delivery vehicle which can be combined with SPIONs-induced hyperthermia for bladder cancer therapy.  相似文献   

16.
Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging (MRI). In this study, a targeted contrast agent (SM-USPIO) was prepared by conjugating coprecipitated USPIO to a humanized SM5-1 antibody which can specifically react with human hepatocellular carcinoma (HCC) cells. The binding and internalization of SM-USPIO to the HCC cell line ch-hep-3 was confirmed by flow cytometry and confocal microscopy. Furthermore, SM-USPIO was demonstrated to be able to selectively accumulate in the tumor cells, resulting in a marked decrease of MRI T2-weighted signal intensity. Biodistribution studies demonstrated the efficient accumulation of SM-USPIO in the ch-hep-3 tumor in nude mice. The in vivo study in the ch-hep-3 tumor-bearing nude mice indicated that MRI using the SM-USPIO as contrast agent possessed good diagnostic ability, suggesting that SM-USPIO had the potential to be a promising targeted contrast agent for diagnosis of HCC.  相似文献   

17.
Glucans are reported to elicit immune responses through activation of macrophages by a specific interaction of β-glucan with an immune cell-specific (1,3)-β-d-glucan receptor or Dectin-1 receptor. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with β-glucan in order to target the immune cells residing in the metastatic liver as an aid for discriminating metastasized tumor regions from normal hepatic parenchymal tissue. The morphology of prepared β-glucan-coated SPIONs (Glu-SPIONs) was characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The cytotoxicity of Glu-SPIONs was analyzed and compared to that of dextran- and PVA-coated SPIONs. The uptake of Glu-SPIONs by peritoneal macrophages was also confirmed with Prussian blue staining and MRI phantom tube imaging. The in vivo uptake of Glu-SPIONs in liver and lymph nodes in a metastatic mouse liver model was tracked by MR imaging after the systemic injection. The Glu-SPIONs predominantly accumulated in the macrophages surrounding the metastatic regions of the liver thereby indicating the distribution of tumor cells in the liver. MR imaging of the Glu-SPIONs clearly revealed macro- or micro-metastasized tumor regions throughout the liver, due to the preferential uptake of Glu-SPIONs into macrophages, not tumor cells. The Glu-SPION-accumulating regions were further confirmed with H&E and Prussian blue stainings after tissue sectioning. Based on our study, we propose that Glu-SPIONs can be successfully applied for diagnosing hepatic metastasis.  相似文献   

18.
Böhm I 《Molecular imaging》2011,10(4):270-277
The purpose of this article is to present a user-friendly tool for quantifying the iron content of superparamagnetic labeled cells before cell tracking by magnetic resonance imaging (MRI). Iron quantification was evaluated by using Prussian blue staining and spectrophotometry. White blood cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Labeling was confirmed by light microscopy. Subsequently, the cells were embedded in a phantom and scanned on a 3 T magnetic resonance tomography (MRT) whole-body system. Mean peak wavelengths λ(peak) was determined at A(720 nm) (range 719-722 nm). Linearity was proven for the measuring range 0.5 to 10 μg Fe/mL (r = .9958; p = 2.2 × 10(-12)). The limit of detection was 0.01 μg Fe/mL (0.1785 mM), and the limit of quantification was 0.04 μg Fe/mL (0.714 mM). Accuracy was demonstrated by comparison with atomic absorption spectrometry. Precision and robustness were also proven. On T(2)-weighted images, signal intensity varied according to the iron concentration of SPIO-labeled cells. Absorption spectrophotometry is both a highly sensitive and user-friendly technique that is feasible for quantifying the iron content of magnetically labeled cells. The presented data suggest that spectrophotometry is a promising tool for promoting the implementation of magnetic resonance-based cell tracking in routine clinical applications (from bench to bedside).  相似文献   

19.
Human umbilical cord mesenchymal stem cells (hUC‐MSCs) transplantation has been shown to promote regeneration and neuroprotection in central nervous system (CNS) injuries and neurodegenerative diseases. To develop this approach into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Neural precursor cells and hematopoietic stem cells can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticle. The purpose of our study was to prospectively evaluate the influence of SPIO on hUC‐MSCs and the feasibility of tracking for hUC‐MSCs by noninvasive imaging. In vitro studies demonstrated that magnetic resonance imaging (MRI) can efficiently detect low numbers of SPIO‐labeled hUC‐MSCs and that the intensity of the signal was proportional to the number of labeled cells. After transplantation into focal areas in adult rat spinal cord transplanted SPIO‐labeled hUC‐MSCs produced a hypointense signal using T2‐weighted MRI in rats that persisted for up to 2 weeks. This study demonstrated the feasibility of noninvasive imaging of transplanted hUC‐MSCs. J. Cell. Biochem. 108: 529–535, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

20.
Magnetic iron oxide nanoparticles are a well-explored class of nanomaterials known for their high magnetization and biocompatibility. They have been used in various biomedical applications such as drug delivery, biosensors, hyperthermia, and magnetic resonance imaging (MRI) contrast agent. It is necessary to surface modify the nanoparticles with a biocompatible moiety to prevent their agglomeration and enable them to target to the defined area. Dendrimers have attracted considerable attention due to their small size, monodispersed, well-defined globular shape, and a relative ease incorporation of targeting ligands. In this study, superparamagnetic iron oxide nanoparticles were synthesized via a coprecipitation method. The magnetic nanoparticles (MNPs) had been modified with (3-aminopropyl) triethoxysilane, and then polyamidoamine functionalized MNPs had been synthesized cycling. Various characterization techniques had been used to reveal the morphology, size, and structure of the nanoparticles such as scanning electron microscopy, transmission electron microscope, X-ray diffraction analysis, and vibrating sample magnetometer, Fourier-transform infrared spectroscopy and zeta potential measurements. In addition, the cytotoxicity property of G3–dendrimer functionalized MNPs were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay which confirmed the biocompatibility of the nanocomposites. Dendrimer functionalized MNPs are able to act as contrast agents for MRI and magnetic fluid hyperthermia mediators. A superior heat generation was achieved for the given concentration according to the hyperthermia results. MRI results show that the synthesized nanocomposites are a favorable option for MRI contrast agent. We believe that these dendrimer functionalized MNPs have the potential of integrating therapeutic and diagnostic functions in a single carrier.  相似文献   

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