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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.
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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.
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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)
Subject(s)
Humans , Animals , Xenobiotics/analysis , Metal Nanoparticles/analysis , Ecotoxicology/methods , Toxicity Tests, Acute/methodsABSTRACT
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.
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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.
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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.
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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.
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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.
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Objective To investigate the cytotoxicity of superparamagnetic iron oxide nanoparticles (SPIONs) modified by chitosan or sodium oleate, so as to provide experimental evidence for future clinical application. Methods The morphology of chitosan-SPIONs or sodium oleate-SPIONs was observed by transmission electron microscope (TEM). Human lung adenocarcinoma A549 cells were treated with 10 μ/mL chitosan-SPIONs or sodium oleate-SPIONs; prussian blue staining was performed to observe the intracellular distribution of the two modified SPIONs. Chitosan-SPIONs or oleate-SPIONs of different concentrations (0, 25, 50, 100, and 200 μ/mL) were used to treat A549 cells and then MTT assay was used to detect cell proliferation. The activity of LDH in the supernatant of A549 cells was tested 48 h after treatment with chitosan- SPIONs or sodium oleate-SPIONs; furthermore, cell apoptosis was analyzed by DAPI staining. Results (1) Both the chitosan- SPIONs and sodium oleate-SPIONs exhibited structure of spherical crystallization, with a diameter of 20-30 nm. The thermal vibrational energy could overcome the magnetic attraction among the SPIONs, presenting superparamagnetism. (2) Prussian blue staining showed blue deposits in the cells, indicating that the two kinds of SPIONs entered the cytoplasm of A549 cells. (3) MTT assay results showed that chitosan-SPIONs hardly affected cell growth, while sodium oleate-SPIONs (200 μ/mL) inhibited the proliferation of A549 cells after 48 h and 72 h (P<0. 05). (4) The LDH activity in the supernatant of A549 cells treated with 200 μ/mL chitosan-SPIONs was significantly higher than that in the control group (P<0. 05), while the LDH activities in 100 μ/mL and 200 μ/mL sodium oleate-SPIONs groups were significantly higher than those in the control group (P<0. 05) and corresponding chitosan-SPIONs group(P<0. 05). (5) The results of DAPI dye showed no significant difference between the chitosan-SPIONs group and the control group, while the cells treated with sodium oleate-SPIONs displayed typical apoptosis characteristics, such as nuclear shrinkage and fragmentation, with the apoptosis rate being significantly higher than that of the control group(P<0. 05). Conclusion It is suggested that chitosan-SPIONs have slighter cytotoxicity to A549 cells compared with sodium oleate-SPIONs.
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This study was investigated the change of concentration and toxicity of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) on tissues of Sprague-Dawley rats. TCL-SPION at the dose of 15 mg/kg body weight was intravenously injected into the tail vein of the male Sprague-Dawley rats. The fate of TCL-SPION in serum, urine and tissues was observed during 28 days. Serum iron level was maximal at 0.25 h post-injection and gradually declined thereafter. In addition, the sinusoids of liver and the red pulp area of spleen were mainly accumulated iron from 0.5 h to 28-day post-injection. In kidney, iron deposition was detected in the tubular area until 0.5 h after injection. Malondialdehyde concentration in the liver slightly increased with time and was not different with that at zero time. In the liver and spleen, TNF-alpha and IL-6 levels of TS treated with TCL-SPION were not different with those of the control during the experimental period. From the results, TCL-SPION could stay fairly long-time in certain tissues after intravenous injection without toxicity. The results indicated that TCL-SPION might be useful and safe as a contrast for the diagnosis of cancer or a carrier of therapeutic reagents to treat diseases.
Subject(s)
Animals , Humans , Male , Rats , Body Weight , Diagnosis , Indicators and Reagents , Injections, Intravenous , Interleukin-6 , Iron , Kidney , Liver , Malondialdehyde , Nanoparticles , Rats, Sprague-Dawley , Spleen , Tumor Necrosis Factor-alpha , VeinsABSTRACT
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.
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A wide variety of nanomaterials have demonstrated promise in medical applications such as drug delivery and imaging. In these applications, the surface chemistry of the materials is critical as it plays an important role in determining the toxicity and biodistribution behavior of the material. We review here the functionalization of nanomaterials with dendrons as an efficient method to alter the surface chemistry of the materials, introducing new properties and functions. Described here is the functionalization of superparamagnetic iron oxide nanoparticles (SPIO) with dendritic guanidines to enhance their transport into cells for magnetic resonance imaging applications. The introduction of dendrons bearing peripheral hydroxyls, amines, guanidines, carbohydrates and Gd(III) chelates to polymer vesicles (polymersomes) is also described. These dendritic moieties allow for modulation of toxicity, cell uptake, protein binding, and contrast agent efficiency, while at the same time allowing the stabilities of the polymersomes to be maintained. Thus, this approach holds promise for the development of a wide range of multifunctional materials for pharmaceutical applications.
Uma grande variedade de nanomateriais tem demonstrado aplicações médicas promissoras, tais como liberação de fármacos e em imagens. Nestas aplicações, a superfície química dos materiais é crítica, uma vez que exerce papel importante na determinação da toxicidade e comportamento de biodistribuição do material. Aqui, nós revisamos a funcionalização de nanomateriais, como dendrons, como método eficiente de alterar a superfície química destes compostos, introduzindo novas propriedades e funções. Descritos aqui estão nanopartículas superparamagnéticas de óxido de ferro (do inglês, SPIO), com guanidinas dendríticas para aumentar seu transporte para o interior das células, úteis em imagens de ressonância magnética. A introdução de dendrons contendo hidroxilas, aminas, guanidinas, carboidratos e quelatos de Gd(III) periféricos em vesículas poliméricas (polymersomes) também está descrita. Esses grupos dendríticos permitem a modulação de toxicidade, captura celular, ligação à proteína e eficiência como agente de contraste, enquanto que, ao mesmo tempo, permitem a manutenção da estabilidade das vesículas poliméricas. Assim, essa abordagem é promissora para o desenvolvimento de grande variedade de materiais multifuncionais para aplicações farmacêuticas.
Subject(s)
Nanostructures/analysis , Dendrimers/classification , Polymers , Magnetite Nanoparticles/classificationABSTRACT
Free Cy5.5 dye and Cy5.5-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) have been routinely used for in vivo optical imaging. However, there is little information about the distribution and accumulation of free Cy5.5 dye and Cy5.5-labeled TCL-SPION in the tissues of mice. Free Cy5.5 dye (0.1 mg/kg body weight) and Cy5.5-labeled TCL-SPION (15 mg/kg body weight) were intravenously injected into the tail vein of ICR mice. The biodistribution and accumulation of the TCL-SPION and Cy5.5 were observed by ex vivo optical imaging and fluorescence signal generation at various time points over 28 days. Cy5.5 dye fluorescence in various organs was rapidly eliminated from 0.5 to 24 h post-injection. Fluorescence intensity of Cy5.5 dye in the liver, lung, kidney, and stomach was fairly strong at the early time points within 1 day post-injection. Cy5.5-labeled TCL-SPION had the highest fluorescence density in the lung at 0.5 h post-injection and decreased rapidly over time. Fluorescence density in liver and spleen was maintained over 28 days. These results suggest that TCL-SPION can be useful as a carrier of therapeutic reagents to treat diseases by persisting for long periods of time in the body.
Subject(s)
Animals , Male , Mice , Carbocyanines/pharmacology , Ferric Compounds/pharmacology , Fluorescent Dyes/pharmacology , Kinetics , Mice, Inbred ICR , Nanoparticles/metabolism , Time Factors , Tissue DistributionABSTRACT
OBJECTIVE: To improve superparamagnetic iron oxide nanoparticles (SPIO-NP) stability, biocompatibility and tumor-targeting and evaluate their tumor targeting in vitro. METHODS: The folic acid-carboxymethylchitosan-superparamagnetic iron oxide nanoparticles (FA-OCMCS-SPIO-NPs) were synthesized by "three-steps": at first, superparamagnetic oxide iron nanoparticles were synthesized by coprecipitation, then, O-carboxymethyl chitosan and folic acid were successfully immobilized on the surface of SPIO-NPs in turn. The fourier transform infrared spectroscopy, X-Ray diffraction were used to confirm their synthesis, meanwhile, transmission electron microscope (TEM), dynamic light scattering (DLS), Zeta-potential measurement and vibrating sample magnetometry (VSM) were applied to characterize their physicochemical properies. Ferrozine assay and Prussian blue staining were used to evaluate their tumor targeting in vitro. RESULTS: X-Ray diffraction showed the crystalline powder of FA-CMCS-SPIO-NPs agree with the standard Fe3O4, Fourier transform infrared results showed O-carboxymethylchitosan and folic acid were covalently modified on the surface of SPIO-NPs successfully, TEM showed all synthesized SPIO-NPs were almost spherical or ellipsoidal. Their sizes were less then 20 nm, dynamic light scattering (DLS), Zeta-potential results demonstrate the intensity particle size distributions of FA-OCMCS-SPIO-NPs were (41.4±0.132)nm, Zeta potential were (-21.36±15)mV. The surface modification may lead to decrese of magnetisms Ferrozine assay and Prussian blue staining results showed FA-OCMCS-SPIO-NPs had good tumor targeting and the tumor targeting had good relations with the amount of FR on surface of tumor cells. CONCLUSION: FA-OCMCS-SPIO-NPs with strong superparamagnetic property, excellent stability, and good folate receptor targeting is successfully synthesized, which demonstrated the potential for tumor MRI diagnose and therapy.