Application status of superparamagnetic iron oxide in sentinel lymph node biopsy for breast cancer / 国际外科学杂志

The axillary lymph node status is the most important prognostic index of breast cancer, so the accurate assessment of axillary lymph node metastasis has always been a hot topic in breast cancer research. Today, sentinel lymph node biopsy (SLNB) has become the preferred surgical procedure for axillary lymph node negative early breast cancer. The selection of tracers is also a key link in the study of SLNB and lymphatic drainage area of breast cancer. Traditional tracers (blue dye, nuclide and fluorescent tracers, etc.) have many problems, such as allergy, poor localization specificity and radioactivity to human body, which limit their promotion and application in clinic. However, superparamagnetic iron oxide nanoparticle (SPION) can effectively improve these shortcomings and has the advantages that other tracers cannot replace. It can be an ideal tracer for SLNB of breast cancer and has a good application prospect. This article mainly describes the current application of SPION in SLNB of breast cancer, and outlines the advantages and disadvantages of this tracer.

Effect of nanoparticles carrying chondroitin sulfate ABC on the migration of schwann cells in a magnetic field / 中国组织工程研究

BACKGROUND: The clinical effect of spinal cord injury is usually unfavorable due to the lack of axon regeneration and the formation of glial scar. Schwann cells, as the support cells for nerve regeneration, have poor migration ability in the central nervous system with abundant astrocytes, which limit its effect on axon regeneration. OBJECTIVE: To explore the effect on the migration of Schwann cells containing superparamagnetic nanoparticles loaded with chondroitinase ABC (ChABC) in the region of astrocytes in the external magnetic field. METHODS: Schwann cells and astrocytes were extracted from sciatic nerves and brachial plexus and cerebral cortex of Sprague-Dawley rats of postnatal day 1 to 3. Cell purity was identified by immunofluorescence staining. The toxicity of superparamagnetic nanoparticles (PEI-SPIONs) to Schwann cells was analyzed by live/dead cell staining. Schwann cells were transfected with PEI-SPIONS in an external magnetic field of 1.4Td for 2 days. The optimal transfection concentration of PEI-SPIONS used was 2 mg/L and the optimal mass ratio of PEI-SPIONS to ChABC was 1:4. Cell migration test was used to evaluate the migration ability of not-treated Schwann cells, PEI-SPIONs/ ChABC transfected Schwann cells, and PEI-SPIONs/ChABC transfected Schwann cells in an external magnetic field. RESULTS AND CONCLUSION: The purity of Schwann cells and astrocytes reached to (91.7±1.2)% and (93.3±2.2)%, respectively. Compared with the Schwann cells group, the number of PEI-SPIONs/ChABC-transfected Schwann cells that entered the region of astrocytes was significantly increased (P < 0.05). Under the external magnetic field, the number of PEI-SPIONs/ChABC-transfected Schwann cells that entered the region of astrocytes and the cell migration distance were significantly increased as compared with the Schwann cells group (P < 0.005). In summary, PEI-SPIONs/ChABC transfection can enhance the ability of Schwann cells to break the glial scar, and increase the fusion of astrocytes. Under the guidance of external magnetic field, the migration ability of Schwann cells is significantly elevated. This method may be a new strategy to promote nerve regeneration after spinal cord injury.

Endothelial progenitor cells in the peripheral blood of patients with moyamoya disease labeled with superparamagnetic iron oxide in vitro for MRI detection

Moyamoya disease (MMD) is currently thought to involve endothelial progenitor cells (EPCs). We investigated whether superparamagnetic iron oxide (SPIO) can be used to label EPCs. Mononuclear cells from 10 moyamoya disease patients were isolated, and cluster of differentiation 133 (CD133) positive cells sorted by magnetic-activated cell sorting were cultured in vitro. The positive rates of CD133, vascular endothelial growth factor receptor (VEGFR)-2, and cluster of differentiation 34 (CD34) were detected by flow cytometry. The cells were co-cultured with fluorescence labeled Dil-acetylated-low-density lipoprotein (Dil-ac-LDL) and Ulex europaeus agglutinin-1 (UEA-1) to observe the endocytosis of Dil-ac-LDL and binding to UEA-1. Prussian blue staining and transmission electron microscopy were used to observe the endocytosis of different SPIO concentrations in EPCs, and CCK-8 was used to detect proliferation of cells transfected with different concentrations of SPIO. T2 weighted imaging (T2WI) signals from magnetic resonance imaging after SPIO endocytosis were compared. Positive rates of CD133, VEGFR-2, and CD34 on sorted mononuclear cells were 68.2±3.8, 57.5±4.2, and 36.8±6.5%, respectively. The double-positive expression rate of CD34 and VEGFR-2 was 19.6±4.7%, and 83.1±10.4% of cells, which showed the uptake of Dil-ac-LDL and binding with UEA-1. The labeling efficiencies of SPIO at concentrations of 25 and 50 μg/mL were higher than for 12.5 μg/mL. The proliferation of cells was not influenced by SPIO concentrations of 12.5 and 25 μg/mL. After labeling, the T2WI of EPCs was reduced. The concentration of 25 μg/mL SPIO had high labeling efficiency detected by magnetic resonance imaging (MRI) without decreased EPCs viability.

In vitro study of GOD/Fe3O4 loaded PLGA nanoparticles in the treatment of retinoblastoma / 解放军医学杂志

Objective To evaluate the therapeutic potential of a novel type of Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with glucose oxidase (GOD)/superparamagnetic iron oxide nanoparticles (Fe3O4Nps) on retinoblastoma (RB) cells in vitro. Methods PLGA nanoparticles loaded with GOD/Fe3O4 (PFG) were prepared by double emulsification. Their particle size, potential, external morphology, and internal structure were examined. Particles that made of PLGA (control), PLGA loaded with GOD (PG), and PLGA loaded with Fe3O4 (PF) are served as control. Y79 cells that were incubated with different particles are termed control group, PF group, PG group, and PFG group. After co-incubation with nanoparticles, cell viability, and reactive oxygen species production were detected. Results PLGA nanoparticles loaded with GOD/Fe3O4 were successfully prepared. The form of PLGA nanoparticles was uniform and showed a round shape with a diameter of 299.3 nm. The nanoparticles were engulfed by Y79 cells after co-incubation with Y79 cells, producing a large number of reactive oxygen species. Cytotoxicity test results showed that the cell viability of Y79 cells in PLGA nanoparticle group coated with GOD/Fe3O4 [(53.648±2.565)%] was significantly lower than that in control group [(100.028±4.491)%], PF group [(97.782±17.520)%] or PG group [(87.438±3.537)%](F=21.226, P<0.01); The cell viability of Y79 cells in 0.25 μg/ml PFG nanoparticle group [(51.770±1.529)%] was significantly lower than that in control group [(100.000±5.021)%], 0.0625 μg/ml group [(85.723±6.903)%] and 0.125 μg/ml group [(74.535±8.282)%] (F=34.593, P<0.05). Massive cell death was detected in the PFG group under laser confocal microscope. Conclusions The novel type of PLGA nanoparticles loaded with GOD/Fe3O4 toxic to Y79 tumor cells with a good reactive oxygen generation ability. It provides a potential treatment for RB.

USPIO-enhanced MRI for lymph-node metastases from abdominal and pelvic malignancies: Meta-analysis / 中国医学影像技术

Objective To investigate value of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI in diagnosis of lymph node metastasis from abdominal and pelvic malignancies with Meta-analysis.Methods A systematic search was conducted in PubMed,Embase,Cochrane Library,Wanfang,VIP and CNKI databases.The literature were screened according to inclusion and exclusion criteria,and four tabular data were extracted.With Meta Disc version 1.4 and STATA 11.0 software,statistical analysis was performed and heterogeneity of the included articles was tested.Based on the result of heterogeneity test,proper effect model was selected to calculate the pooled sensitivity and specificity.Summary receiver operating characteristics curve was obtained,and the area under curve (AUC) was calculated.Results Totally 20 English literature were enrolled,including 1 211 patients and 3 583 lymph nodes.The pooled sensitivity and specificity for USPIO-enhanced MRI in diagnosis of lymph node metastasis was 0.89 (95％CI [0.86,0.91]) and 0.96 (95 ％CI [0.95,0.96]),and AUC was 0.98,respectively.Regression analysis revealed that the heterogeneity may result from the location of tumors,and subgroup analysis showed that pooled sensitivity in diagnosis of lymph node metastasis in abdominal malignancies was good.Conclusion USPIO-enhanced MRI has good diagnostic efficacy in diagnosis of lymph node metastasis from abdominal and pelvic malignancies.

Quantitative MRI of SD-rat adipose derived stem cells labeled with a new type paramagnetic nanoparticles in rats in vivo / 中国介入影像与治疗学

Objective To explore the feasibility of tracking migration and distribution of SD-rat adipose derived stem cells (ADSCs) labeled with Polyethylene Glycol/Polyehthyleneimine modified superparamagnetic iron oxide (PEG/PEI-SPIO) in rats with chronic cerebral ischemia using MRI.Methods Thirty female SD rats underwent permanent occlusion of bilateral common carotid arteries 6 months were divided into PEG/PEI-SPIO labeled group and unlabeled group (each n =15).Labeled or unlabeled ADSCs suspension was injected into the right ventricle of rats in two groups,respectively.MR scans were performed at the 7th,14th and 21st day after transplantation for each 5 rats.T2 value of T2mapping sequence in hippocampus,cortex and cerebellum were measured.Then the rats were scarified,and the brains were obtained,and Prussia dyeing was performed.Under high magnification,blue dye cells at each time points and brain area were counted.T2 values and blue dye cells were statistically analyzed.Results Class round hypointensity areas were detected in temporol-parietal cortex and hippocampus in both groups on T2WI,T2* WI and SWI.T2 value of the right temporolparietal cortex and hippocampus in the labeled group was shorter than those of the unlabeled group on the 14th day after transplantation (P=0.013,0.045).T2 value of the right temporol-parietal cortex in the labeled group was shorter than that of the unlabeled group on the 21st day after transplantation (P=0.007).The number of blue dye cell of the right temporol-parietal cortex on the 14th and 21th day,hippocampus on the 14th day in the labeled group were more than those of the unlabeled group after transplantation (P=0.029,0.032,0.043).Conclusion ADSCs labeled with PEG/PEI-SPIO transplanted into lateral ventricle of SD rat could migrate to the damaged areas caused by chronic cerebral ischemia.It is possible to use quantitative MRI to track migration and distribution of ADSCs labeled with PEG/PEI-SPIO in rat brain.

Ecotoxicidad de nanopartículas metálicas y superparamagnéticas de óxido de hierro en dos especies / Ecotoxicity of metalic and superparamagnetics iron oxide nanoparticles in two species

Introducción: la nanotecnología y el empleo de materiales a nano escala son un área relativamente nueva de la ciencia y la tecnología con un gran crecimiento en el mercado global. Muchos de los productos no cuentan con estudios que garanticen su uso seguro, tanto para el hombre como para los ecosistemas. Los estudios ecotoxicológicos permiten evaluar los efectos de un determinado xenobiótico sobre especies representativas de los diferentes compartimentos ambientales. Objetivo: evaluar los efectos tóxicos de nanopartículas de Ag, Au, Ag/Ag y superparamagnéticas de óxido de hierro, en dos especies bioindicadoras de los ecosistemas terrestre y acuático. Métodos: como parte de los estudios de seguridad se realizaron ensayos de toxicidad aguda por contacto en lombriz de tierra de la especie Eisenia andrei, con una duración de 96 horas y estudios en anfibios de la especie Osteopillus septentrionales en diferentes etapas del desarrollo (embrionario y larval). Se evaluó la ocurrencia de mortalidad y de efectos tóxicos, en el caso del ensayo en lombriz de tierra; se determinó además la viabilidad celular. Resultados: los efectos tóxicos más significativos en el caso de la lombriz de tierra fueron, la ocurrencia de alteraciones fisiológicas y conductuales al ser expuesta a NPs de Ag de 3 nm y superparamagnéticas de óxido de hierro, estas últimas provocaron citotoxicidad a la concentración 1,38 mg/mL. En el caso de los anfibios se evidenció toxicidad en NPs de Ag 3 nm y superparamagnéticas de óxido de hierro. Conclusiones: todas las nanopartículas mostraron efectos tóxicos en las especies bioindicadoras evaluadas(AU)

Introduction: Nanotechnology and the use of nanoscale materials are a relatively new area of science and technology with big growth in the global market. Many of these products don't have studies that guarantee their safe use, both for man and for ecosystems. Ecotoxicological studies allow the evaluation of the effects of a particular xenobiotic on representative species of the different environmental compartments. Objective: To evaluate the toxic effects of nanoparticles of Ag, Au, Ag / Ag and super paramagnetic iron oxide in two bioindicators of terrestrial and aquatic ecosystems. Methods: Acute contact toxicity tests were carried out on ground worm of the Eisenia andrei species, with a duration of 96 hours and studies on amphibians of the species Osteopillus septentrionales at different stages of development (embryonic and larval). The occurrence of mortality and toxic effects was evaluated in the case of earthworm test; cell viability was also determined. Results: The most significant toxic effects in the case of earthworms were the occurrence of physiological and behavioral alterations when exposed to 3 nm Ag of superparamagnetic iron oxide nanoparticles, where the latter caused cytotoxicity at concentration of 1.38 mg / mL. In the case of amphibians, toxicity was evidenced in Ag 3 nm nanoparticles and superparamagnetic iron oxide. Conclusions: All nanoparticles showed toxic effects in the evaluated bioindicator species(AU)

Transhepatic arterial embolization with superparamagnetic iron oxide and lipiodol for the treatment of VX2 tumor in rabbits / 中南大学学报(医学版)

Objective:To evaluate the feasibility and therapeutic efficacy of transhepatic arterial embolization with superparamagnetic iron oxide (SPIO) and lipiodol (LIP) for the treatment of VX2 tumor in rabbits.Methods:Twenty-four rabbits with hepatic VX2 tumors by surgical implantation were randomly divided into 4 groups and treated with transhepatic arterial embolization of 4 different agents as follows (n=6 each):doxorubicin (DOX) group,DOX-LIP group,SPIO-DOX group,and SPIO-DOX-LIP group.Liver function (AST and ALT) was measured at 0,1,3,5 and 7 d after transhepatic arterial embolization.The serum DOX level was measured at 0,5,15,30,60,and 120 minutes after transhepatic arterial embolization.MRI was performed at 7 d after the treatment to assess the distribution of SPIO in the SPIO-DOX group and SPIO-DOX-LIP group,while CT was performed to assess the distribution of LIP in the DOX-LIP group and SPIO-DOX-LIP group.All the rabbits were sacrificed and their livers were removed at 7 d after treatment for the detection of tissue DOX level.The histopathologic examinations were performed including HE staining,Prussian blue staining and TUNEL assay,and then the tumor necrosis percentage and apoptosis index were calculated.Results:Compared to the DOX group,the levels of AST and ALT in other 3 groups were significantly elevated at 1 and 3 d after embolization (P＜0.05).The levels of ALT and AST in the DOX group,DOX-LIP group or SPIO-DOX-LIP group returned to the baseline at day 7,there were no significant differences (P＞0.05).The SPIO-DOX-LIP group exhibited the lowest serum DOX level at all time points up to 120 minutes after embolization (P＜0.05).However,the tissue DOX level in the SPIO-DOX-LIP group was the highest among all groups at day 7 (P＜0.05).The SPIO-DOX group and SPIO-DOX-LIP group showed significantly lower MRI signal intensity of tumors in T2 weighted imaging (T2WI) at day 7.Meanwhile DOX-LIP group and SPIO-DOX-LIP group showed that high-density lipiodol was deposited in the tumors in CT images.Histopathologic findings showed an almost complete central necrosis coagulation of tumors in the SPIO-DOX-LIP group,and the tumor necrosis percentage and tumor apoptosis index were significantly increased in the SPIO-DOX-LIP group compared to those in other 3 groups (P＜0.05).Conclusion:This novel drug-delivery system of SPIO nano-drug carrier together with LIP is safe and feasible when it is used for transhepatic arterial embolization for liver tumor.It provides an excellent MR and CT visualization and improves the therapeutic efficacy for the treatment of rabbit VX2 liver tumor.

MR molecular imaging of pancreatic cancer cell targeted by superparamagnetic iron oxide nanoparticles / 中国医学影像技术

Objective To explore the feasibility of MR molecular imaging in human pancreatic cancer cell (BxPC-3 cell) targeted by superparamagnetic iron oxide nanoparticles (SPION).Methods Both MUC1 SPION probes with MUC1 targeted modification (targeted group) and bull serum albumin (BSA)-SPION as the control (non targeted group) were prepared.The cytotoxicity of MUC1 SPION in different concentrations (0,6.25,12.50,25,50,100,200 μg/ml) was verified by MTT (3 [4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay.BxPC-3 cells were cultured with MUC1-SPION (targeting group) and BSA-SPION (control group) in different concentration as 50,100,200 μg/ml,respectively for 2 h.Then MRI scans were performed,the transverse relaxation time (T2) value and the enhancement ratio of T2 were recorded and calculated.The combination conditions of targeting probes and cells were observed by prussian blue staining.Results The cell cytotoxicity of MUC1 SPION in different concentrations showed no statistical difference according to MTT assay (F=1.74,P 0.18).There were statistical differences of the T2 value and the enhancement ratio of T2 for the concentration as 50,100,200 μg/ml,respectively (all P＜0.05).More blue particles were observed by prussian blue staining in targeted group than in non targeted group.Conclusion MUC1-SPION has favourable targeting ability to BxPC 3 cell,and MRI of BxPC-3 cell targeted by SPION is satisfied security and feasibility.

MR molecular probes RGD-USPIO in evaluation effect of ucleoside combination on human hepatoma cell line Bel-7402 in vitro / 中国医学影像技术

Objective To evaluate the effect and the anti-tumor mechanism of nucleoside combination on human hepatoma cell line Bel-7402 with Arg-Gly-Asp sequence labeled by ultrasmall superparamagnetic iron oxide (RGD-USPIO).Methods The tumor cells Bel-7402 of logarithmic phlyhase were divided into experimental group and control group,treated with 1 mmol/L nucleoside combination and 1640 medium respectively.The two group were co-cultured for 48 h,and were added RGD-USPIO and co-cultured for 6 h.Then the two groups were proceeded with MR scanning,and the signal intensity of T2WI were measured.After extraction of the total RNA and protein of experiment group and control group,the expression of integrin avβ3 was detected using real-time PCR and Western blot.Results The T2WI signal intensity of experimental group (997.35±42.83) was higher than that of control group (241.05±15.36,t 28.79,P＜0.01).Compared with control group,the expression of integrin αvβ3 mRNA in experimental group was (0.22±0.02) times (t=4.50,P＜0.01).According to Western blot,the protein bands of experimental group were relatively lighter than that of control group,the expression of integrin αvβ3 in experimental group was lower (t =11.88,P＜0.01).Conclusion Nucleoside combination has anti-tumor effect by inhibiting integrin ligand-receptor binding,and the anti tumor mechanism may be related to the induction of tumor cell apoptosis.MR molecular probes can conveniently and accurately evaluate the anti-tumor effect of nucleoside combination on Bel-7402 cells.

Superparamagnetic iron oxide nanoparticle targeting of adipose tissue-derived stem cells in diabetes-associated erectile dysfunction / 亚洲男科学杂志(英文版)

Erectile dysfunction (ED) is a major complication of diabetes, and many diabetic men with ED are refractory to common ED therapies. Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in diabetic animal models. However, inadequate cell homing to damaged sites has limited their efficacy. Therefore, we explored the effect of ADSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) on improving the erectile function of streptozotocin-induced diabetic rats with an external magnetic field. We found that SPIONs effectively incorporated into ADSCs and did not exert any negative effects on stem cell properties. Magnetic targeting of ADSCs contributed to long-term cell retention in the corpus cavernosum and improved the erectile function of diabetic rats compared with ADSC injection alone. In addition, the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. Accordingly, magnetic field-guided ADSC therapy is an effective approach for diabetes-associated ED therapy.

Preparation of anti-EGFR-PEG-SPIO molecular probe and its targeting MRI for lung adenocarcinoma cells / 中国医学影像技术

Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR),as well as the feasibility for surveillance of tumor targeting with MRI.Methods Nanoparticles (NPs)of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared,and the morphology of nanoparticles was observed with transmission electron microscope (TEM).The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI.MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro.The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM.Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI,decreased significantly compared with PEG-SPIO.The rate of signal intensity change was -58.2％,-82.7％,-94.4％ and-98.3％,respectively,at iron concentrations of (0,10,20,40,80 μg/ml) of antiEGFR-PEG-SPIO.Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells,but few of PEG-SPIO.Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro,and the targeting delivery process could be monitored with 3.0T MRI.

Research progresses of superparamagnetic iron oxide nanoparticles in precision medicine / 中国医学影像技术

The demand for diagnosis and therapy of diseases should be higher in the era of precision medicine.The superparamagnetic iron oxide nanoparticles (SPION) is used in diagnosis,therapy,and monitor of diseases due to its good superparamagnetism,which has always been paid more attention in molecular imaging.The research progresses of SPION in precision medicine were reviewed in this article.

Hypoxia Enhances the Therapeutic Potential of Superparamagnetic Iron Oxide-labeled Adipose-derived Stem Cells for Myocardial Infarction / 华中科技大学学报（医学）（英德文版）

Adipose-derived stem cells (ASCs) induce therapeutic angiogenesis due to pro-angiogenic cytokines secretion.Superparamagnetic iron oxide (SPIO) nanoparticles are critical for magnetic resonance (MR) tracking of implanted cells.Hypoxia is a powerful stimulus for angiogenic activity of ASCs.In this study,we investigated whether therapeutic potency could be enhanced by implantation of hypoxia-preconditioned SPIO-labeled ASCs (SPIOASCs) into the infarcted myocardium.ASCs and SPIOASCs were cultured under 2％ O2 (hypoxia) or 95％ air (normoxia).Cells were intramyocardially injected into the infarcted myocardium after 48-h culture.We found that hypoxia culture increased the mRNA expression of hypoxia-inducible factor-1 alpha (HIF-lαt) and vascular endothelial growth factor (VEGF) in ASCs and SPIOASCs.The VEGF protein in the conditioned medium was significantly higher in hypoxic ASCs and SPIOASCs than in normoxic ASCs and SPIOASCs.The capillary density and left ventricular contractile function in the infarcted myocardium were significantly higher 4 weeks after implantation with hypoxic ASCs and SPIOASCs than with normoxic ASCs and SPIOASCs.Improvement in the capillary density and left ventricle function didn't differ between hypoxic ASCs-transplanted rats and hypoxic SPIOASCs-transplanted rats.Hypoxic culture enhanced the angiogenic efficiency of ASCs.It was concluded that implantation of hypoxic ASCs or SPIOASCs promotes therapeutic angiogenesis and cardiac function recovery in the infarcted myocardium.SPIO labeling does not impact the beneficial effect of hypoxic ASCs.

Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, the in vitro efficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells. MATERIALS AND METHODS: Cell viability, reactive oxygen species generation, and apoptosis frequency were assessed in vitro in 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells. RESULTS: Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells. CONCLUSION: These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasis in vivo.

MR study with USPIO and MSLN-USPIO in the nude mouse model bearing human pancreatic carcinoma / 中华胰腺病杂志

Objective To study the potential and value of ultrasmall superparamagnetic iron oxide (USPIO) conjugated by mesothelin antibody as MRI targeting contrast agent for diagnosis of implanted human pancreatic carcinomas in nude mouse.Methods Nude mouse tumor models bearing multiple human pancreatic carcinomas at different time points was established and they were randomized into two groups,and USPIO or MSLN-USPIO were used as contrast enhanced agents in the 3.0T MRI scan,respectively,then the positive detection rates for smallest tumors,and the signal intensity of tumors in T2 mapping images of both unenhanced and contrast enhanced scanning and the negative enhancement rate were measured,then Prussian blue staining was performed in alI the tumor specimens to observe the difference of Fe3 + ion deposition.Results There was no statistical significance between USPIO group and MSLN-USPIO group in the positive detection rates for smallest tumors.In USPIO group,the negative enhancement rate of left or right axilla tumors was (12.29 ±7.45)％ and (11.06 ±5.91)％,and they were (33.88 ±6.09)％ and (43.29 ± 11.64)％ in MSLN-USPIO group.There was statistical significance in the difference of signal intensity between unenhanced and contrast enhanced in left or right axilla tumors (P ＜ 0.05),and the negative enhancement rate in MSLN-USPIO group was significantly higher than that in USPIO group (P ＜0.05).The Fe3+ ion deposition in tumors' tissue in MSLN-USPIO group was significantly more than that in USPIO group.Conclusions The enhanced effect of MSLN-USPIO is superior to USOPIO,and it can be a tumor targeted MR contrast enhanced agent for the diagnosis of pancreatic carcinoma in nude mouse.

Application of superparamagnetic iron oxide nanoparticles in magnetic resonance imaging and drug delivery system / 国际药学研究杂志

Superparamagnetic iron oxide nanoparticles(SPION) as a new type of nano-materials have been widely studied. Because of their super paramagnetic property, targeting, biocompatibility, easy observability, and plasticity, etc., SPION have been used not only as magnetic resonance imaging (MRI) contrast agents in the early diagnosis of clinical cancer, but also as targeting drug carrier to selectively deliver the drugs especially anti-cancer drugs to target lesion, and therefore, improve the bioavailability of the drugs. For these reasons, the research on contrast agents and magnetic targeting drug carrier has attracted widespread attention. This paper reviews the research progress of SPION application in MRI and targeted drug delivery through consulting a number of relevant publications.

Evaluation of Engraftment of Superparamagnetic Iron Oxide-Labeled Mesenchymal Stem Cells Using Three-Dimensional Reconstruction of Magnetic Resonance Imaging in Photothrombotic Cerebral Infarction Models of Rats

OBJECTIVE: To evaluate engraftment by visualizing the location of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) three-dimensionally in photothrombotic cerebral infarction (PTCI) models of rats. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of an agarose block containing superparamagnetic iron oxide (SPIO)-labeled hBM-MSCs was performed using a 3.0-T MRI, T2-(T2WI), T2*-(T2*WI), and susceptibility-weighted images (SWI). PTCI was induced in 6 rats, and 2.5 x 10(5) SPIO-labeled hBM-MSCs were infused through the ipsilateral internal carotid artery (ICA group) or tail vein (IV group). MRI was performed on days 1, 3, 7, and 14 after stem cell injection. Dark signal regions were confirmed using histology. Three-dimensional MRI reconstruction was performed using the clinical workflow solution to evaluate the engraftment of hBM-MSCs. Volumetric analysis of the engraftment was also performed. RESULTS: The volumes of SPIO-labeled hBM-MSCs in the phantom MRI were 129.3, 68.4, and 25.9 microL using SWI, T2*WI, and T2WI, respectively. SPIO-labeled hBM-MSCs appeared on day 1 after injection, encircling the cerebral infarction from the ventral side. Dark signal regions matched iron positive cells and human origin (positive) cells. The volume of the engraftment was larger in the ICA group on days 1, 3, and 7, after stem cell injection (p < 0.05 on SWI). SWI was the most sensitive MRI pulse sequence (p < 0.05). The volume of infarction decreased until day 14. CONCLUSION: The engraftment of SPIO-labeled hBM-MSCs can be visualized and evaluated three-dimensionally in PTCI models of rats. The engraftment volume was larger in the ICA group than IV group on early stage within one week.

Application of superparamagnetic iron oxide nanoparticles in magnetic resonance imaging and drug delivery system / 国际药学研究杂志

Superparamagnetic iron oxide nanoparticles(SPION) as a new type of nano-materials have been widely studied. Because of their superparamagnetic property, targeting, biocompatibility, easy observability, and plasticity, etc., SPION have been used not only as magnetic resonance imaging (MRI) contrast agents in the early diagnosis of clinical cancer, but also as targeting drug carrier to selectively deliver the drugs especially anti-cancer drugs to target lesion, and therefore, improve the bioavailability of the drugs. For these reasons, the research on contrast agents and magnetic targeting drug carrier has attracted widespread attention. This paper reviews the research progress of SPION application in MRI and targeted drug delivery through consulting a number of relevant publications.

Specific MR imaging of hepatocellular carcinoma with VEGF-C targeted USPIO probe in a rat model / 实用放射学杂志

Objective To investigate the potential value of VEGF-C targeted ultrasmall superparamagnetic particles of iron oxide (USPIO)molecular probe in specific detection of hepatocellular carcinoma (HCC)in a rat model using MRI.Methods The targeted probe was synthesized by conjugating VEGF-C antibody with amino modified USPIO.Cell counting kit-8 assay was conducted to as-certain the probe’s effect on the growth of HepG2 cells.Rat models with HCC were divided into two groups (targeted group with VEGF-C-USPlO and a contrast with USPIO)with 3 rats for each group at random.Pre-and post-contrast enhanced MR imaging with different time points of 0.5,1 and 1.5h was performed with an injection into caudal vein.The signal intensities of the tumor on T2 WI and T2 * WI were measured,and the differences of the signal intensities between pre-and post-enhancements or between both groups were analyzed.The iron particles within the tumors in two groups were confirmed by Prussian blue iron staining.The ex-pression of VEGF-C in HCC was proved by immunohistochemistry.Results The signal intensities of HCC on T2 WI and T2 * WI af-ter VEGF-C-USPI0 injection were decreased obviously with a minimum value at 1 h ,indicating a significant difference (P 0.05).Statistical differences in signal inten-sity on T2 * WI after enhancement between both groups were also showed (P <0.05).Prussian blue staining results showed more iron particles within the tumor tissues in VEGF-C-USPI0 group,whereas less ones in USPIO group.Immunohistochemical results showed that VEGF-C was over expressed in cytoplasm and membrane.Conclusion VEGF-C-USPI0 molecular probes can initiatively target to the liver cancer in rat models with expressed VEGF-C,which may help to achieve the specific MR imaging of HCC,indica-ting a potential of the metastasis.