首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 125 毫秒
1.

Introduction

Rheumatoid arthritis (RA) is a chronic disease causing recurring inflammatory joint attacks. These attacks are characterized by macrophage infiltration contributing to joint destruction. Studies have shown that RA treatment efficacy is correlated to synovial macrophage number. The aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (SPION) labeled macrophages to evaluate RA treatment by MRI.

Methods

The evolution of macrophages was monitored with and without dexamethasone (Dexa) treatment in rats. Two doses of 3 and 1 mg/kg Dexa were administered two and five days following induction of antigen induced arthritis. SPIONs (7 mg Fe/rat) were injected intravenously and the knees were imaged in vivo on days 6, 10 and 13. The MR images were scored for three parameters: SPION signal intensity, SPION distribution pattern and synovial oedema. Using 3D semi-automated software, the MR SPION signal was quantified. The efficacy of SPIONs and gadolinium chelate (Gd), an MR contrast agent, in illustrating treatment effects were compared. Those results were confirmed through histological measurements of number and area of macrophages and nanoparticle clusters using CD68 immunostaining and Prussian blue staining respectively.

Results

Results show that the pattern and the intensity of SPION-labeled macrophages on MRI were altered by Dexa treatment. While the Dexa group had a uniform elliptical line surrounding an oedema pocket, the untreated group showed a diffused SPION distribution on day 6 post-induction. Dexa reduced the intensity of SPION signal 50-60% on days 10 and 13 compared to controls (P = 0.00008 and 0.002 respectively). Similar results were found when the signal was measured by the 3D tool. On day 13, the persisting low grade arthritis progression could not be demonstrated by Gd. Analysis of knee samples by Prussian blue and CD68 immunostaining confirmed in vivo SPION uptake by macrophages. Furthermore, CD68 immunostaining revealed that Dexa treatment significantly decreased the area and number of synovial macrophages. Prussian blue quantification corresponded to the macrophage measurements and both were in agreement with the MRI findings.

Conclusions

We have demonstrated the feasibility of MRI tracking of in vivo SPION-labeled macrophages to assess RA treatment effects.  相似文献   

2.
Jiang W  Xie H  Ghoorah D  Shang Y  Shi H  Liu F  Yang X  Xu H 《PloS one》2012,7(5):e37376
Currently, effective and specific diagnostic imaging of brain glioma is a major challenge. Nanomedicine plays an essential role by delivering the contrast agent in a targeted manner to specific tumor cells, leading to improvement in accurate diagnosis by good visualization and specific demonstration of tumor cells. This study investigated the preparation and characterization of a targeted MR contrast agent, transferrin-conjugated superparamagnetic iron oxide nanoparticles (Tf-SPIONs), for brain glioma detection. MR imaging showed the obvious contrast change of brain glioma before and after administration of Tf-SPIONs in C6 glioma rat model in vivo on T2 weighted imaging. Significant contrast enhancement of brain glioma could still be clearly seen even 48 h post injection, due to the retention of Tf-SPIONs in cytoplasm of tumor cells which was proved by Prussian blue staining. Thus, these results suggest that Tf-SPIONs could be a potential targeting MR contrast agent for the brain glioma.  相似文献   

3.
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   

4.
Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.  相似文献   

5.
6.
RNA interference therapy utilizes physiological gene silencing that is originally found as a defense function against foreign RNAs. To silence the target gene, short double stranded RNA has to be delivered to cytosol. However, lack of a suitable delivering carrier is the major obstacle to practical usage. In this study, we present a novel complex consisting of β-1,3-glucan and short interference RNA (siRNA) as a solution for the problem. We used a β-1,3-glucan schizophyllan (SPG) and a siRNA (dA-siTNFα) that is designed to suppress tumor necrosis factor alpha (TNF-α), where the sense strand of siRNA has (dA40) tail to induce complexation with SPG. The dA-siTNFα/SPG complex showed higher affinity to recombinant dectin-1 than SPG itself, where dectin-1 is a β-1,3-glucan receptor expressed on antigen presenting cells and can be a target for specific delivery. The complex suppressed lipopolysaccharide (LPS)-induced TNF-α secretion by peritoneal macrophages in vitro. When the complex was intravenously injected, the oligonucleotide accumulated in liver; especially distributed into Kupffer cells. The complex significantly decreased the serum TNF-α level for the mouse model of LPS-induced acute hepatitis. This new siRNA delivery system may overcome the problem for RNA interference therapy because of its non-toxicity and high target specificity.  相似文献   

7.
Unmethylated CpG sequences (CpG DNA) can induce Th1 response and thus become a potential immunotherapeutic agent. A key step in the treatment is to transport CpG DNA to its receptor TLR9 located in the endocytosis pathway of target immune cells. For the effective transport, we prepared a novel complex from a β-1,3-glucan schizophyllan (SPG) and CpG DNA, and administered the complex to murine peritoneal macrophages that had been previously activated by thioglycollate and expressed a major β-1,3-glucan receptor Dectin-1 on the cellular surface. Flow cytometric analysis and microscopic observation showed that the complex was taken up by the macrophage through Dectin-1 mediated pathway. Indeed, ELISA demonstrated that IL-12 production was increased sigmoidally with increasing SPG/CpG DNA ratio in the complexation, and reached the maximum at the SPG-rich composition. In the present work, we describe a new approach to deliver CpG DNA to immune cells by use of a β-1,3-glucan/DNA complex.  相似文献   

8.
9.
Phagocytes engulf pathogenic microbes, kill them and degrade their cellular macromolecules by hydrolytic enzymes in phagolysosomes. However, such enzymes are unable to degrade some microbial polysaccharides, and fate of such indigestible polysaccharides in phagocytes remains uncertain. Using the extracellular domain of Dectin-1 as β-glucan-specific probes, we succeeded in detection of soluble and Dectin-1-reactive β-glucan discharged from mouse RAW 264.7 and human THP-1 macrophage cell lines as well as mouse peritoneal macrophages, which had phagocytized insoluble β-glucan particles. The RAW 264.7 cell culture-supernatant containing the discharged β-glucan stimulated naïve RAW 264.7 cells, resulting in the induction of cytokine expression. Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186). Moreover, reactive oxygen species (ROS) produced by a Cu2+/ascorbic acid system solubilized insoluble β-glucan particles in vitro, and a part of the solubilized β-glucan was Dectin-1 reactive and biologically active in macrophage activation. The soluble and biologically active β-glucan was degraded further during prolonged exposure to ROS. These results suggest that degraded but Dectin-1-reactive β-glucan is discharged from macrophage cells phagocytizing insoluble β-glucan particles and stimulates not only themselves again but also the other naïve phagocytes, leading to the effective elimination of infecting microbes and the ultimate breakdown and inactivation of metabolically resistant β-glucan.  相似文献   

10.
Previous studies have shown that β-glucans extracted from yeast or fungi potentiate immune responses. In the present study, the immunomodulatory activities of β-(1→3, 1→4)-glucan, derived from oats, were investigated. The ability of oat β-glucan (OβG) to stimulate IL-1 and TNF-α release from murine peritoneal macrophages and the murine macrophage cell line P338D1, was assessed. In vitro stimulation of macrophages with OβG resulted in the production of IL-1 in a dose and time-dependent manner, whereas only small amounts of TNF-α could be detected in the culture supernatants. OβG also induced the production of IL-2, IFN-γ and IL-4 secretion in a dose-dependent manner in cultured spleen cells. The intraperitoneal administration of OβG in mice resulted in the accumulation of leucocytes, predominantly macrophages, in the peritoneal cavity. Furthermore, OβG was tested for its ability to enhance non-specific resistance to a bacterial challenge in mice. Survival of mice challenged with Staphylococcus aureus was enhanced by a single intraperitoneal administration of 500 μg of OβG 3 days prior to bacterial challenge. In conclusion, these studies demonstrated that OβG possesses immunomodulatory activities capable of stimulating immune functions both in vitro and in vivo.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号