Irregular-Shaped Fe3O4 Nanoparticles-Mediated Magneto-Mecha nical Force for Killing Tumor Cell / 医用生物力学

Objective To investigate tumor cell killing effect of superparamagnetic Fe3O4 nanoparticles with cubic phase through magneto-mechanical force under a low-frequency vibrating magnetic field ( VMF). Methods A kind of strong magnetic and irregular-shaped Fe3O4 nanoparticles with cubic phase was synthesized by coprecipitation method. The Fe3O4 nanoparticles were exposed to a self-developed VMF and cell killing efficiency of the Fe3O4-mediated magneto-mechanical force was investigated. Results VMF alone had no effects on cell viability. After Fe3O4 nanoparticles were added, the cell viability significantly decreased with prolonging the VMF treatment time and increasing the Fe3O4 nanoparticle concentration. Lactate dehydrogenase released by damaged cells also increased with prolonging the VMF exposure time. Conclusions The irregular-shaped Fe3O4 nanoparticles can transfer magneto-mechanical force to tumor cells under VMF, cause structural damage of cells and result in cell death. The VMF generator developed in this study has simple structure and it is safe for use and convenient for operation. The developed magnetic nanoparticles and the corresponding cancer cell killing technique have the potential for clinical transformation.

Preparation and targeting evaluation of reductant-sensitive oxaliplatin-loaded Fe3O4 nanoparticles / 药学学报

The non-specific accumulation and release of drugs are the main factors affecting the therapeutic effect as well as causing toxic side effects of chemotherapeutic drugs. Nowadays, the application of nanotechnology and responsive drug release is an important strategy to improve the tumor-specific accumulation of drugs and reduce their side effects. In this study, an α-enolase targeted peptide (ETP)-modified polyethylene glycol poly-lysine block copolymer loaded with oxaliplatin prodrug was synthesized first, and then, polymer-coating Fe3O4 nanoparticles were prepared by phase transfer dialysis method to improve the blood circulation stability and tumor targeting of oxaliplatin. At the same time, the physicochemical properties, reductant-responsive drug release, cellular uptake, tumor targeting and other biological functions of ETP modified oxaliplatin-loaded Fe3O4 nanoparticles were studied in vitro and in vivo. First, the results of reductant-triggered drug release study showed that the drug-loaded nanoparticles could achieve rapid release of more than 80% of the prototype oxaliplatin within 3 h under the reduction conditions simulating the tumor cytoplasmic microenvironment. Secondly, the results of flow cytometry showed that the modification of ETP could increase the ratio of cellular uptake of drug-loaded nanoparticles in tumor cells, and the way that drug-loaded nanoparticles endocytosed by tumor cells were mainly through the energy-dependent and receptor protein and fossin-mediated endocytosis pathway. The animal procedures were approved by the Institutional Animal Care and Use Committee of School of Pharmacy of Fudan University. Moreover, the results of pharmacokinetic experiment showed that the area under the curve (AUC0-∞) of oxaliplatin could be significantly increased by nano-formulation which was about 5 times than that of free oxaliplatin. Besides, the pharmacokinetic results also showed that the drug-loaded Fe3O4 nanoparticles constructed by covalent linkage and chelation had good overall stability in vivo. Finally, the in vivo imaging results showed that ETP modification could increase tumor accumulation of drug-loaded nanoparticles, which would be conducive to the efficacy of oxaliplatin in tumor lesions. In summary, the oxaliplatin-loaded Fe3O4 nanoparticles with the capability of reductant-responsive drug release have good drug release characteristics, blood circulation stability and tumor targeting ability, and have the potential to improve the anti-tumor therapeutic effect of oxaliplatin.

Effects of Fe₃O₄ on the denitrification performance of Pseudomonas stutzeri / 生物工程学报

Biological denitrification is the most widely used technology for nitrate removal in wastewater treatment. Conventional denitrification requires long hydraulic retention time, and the nitrate removal efficiency in winter is low due to the low temperature. Therefore, it is expected to develop new approaches to enhance the denitrification process. In this paper, the effect of adding different concentrations of Fe₃O₄ nanoparticles on the denitrification catalyzed by Pseudomonas stutzeri was investigated. The maximum specific degradation rate of nitrate nitrogen improved from 18.0 h⁻¹ to 23.7 h⁻¹ when the concentration of Fe₃O₄ increased from 0 mg/L to 4 000 mg/L. Total proteins and intracellular iron content also increased along with increasing the concentration of Fe₃O₄. RT-qPCR and label-free proteomics analyses showed that the relative expression level of denitrifying genes napA, narJ, nirB, norR, nosZ of P. stutzeri increased by 55.7%, 24.9%, 24.5%, 36.5%, 120% upon addition of Fe₃O₄, and that of denitrifying reductase Nap, Nar, Nir, Nor, Nos increased by 85.0%, 147%, 16.5%, 47.1%, 95.9%, respectively. No significant difference was observed on the relative expression level of denitrifying genes and denitrifying reductases between the bacteria suspended and the bacteria adhered to Fe₃O₄. Interestingly, the relative expression level of electron transfer proteins of bacteria adhered to Fe₃O₄ was higher than that of the bacteria suspended. The results indicated that Fe₃O₄ promoted cell growth and metabolism through direct contact with bacteria, thereby improving the denitrification. These findings may provide theoretical support for the development of enhanced denitrification.

Preparation and characterization of magnetic chitosan microspheres / 中国组织工程研究

BACKGROUND: As carriers of enzymes, cells and drugs, magnetic polymer microspheres have been widely used in the fields of bioengineering, cytology, and biomedicine. OBJECTIVE: To prepare the magnetic polymer microspheres characterized by small particle size, good dispersion, strong magnetic response, safety, and non-toxicity. METHODS: Magnetic chitosan microspheres were prepared by reverse phase suspension process using Fe3O4 as core, paraffin as dispersed medium, Span-80 as emulsifier, and glutaraldehyde as cross-linking agent. The effects of factors including crosslinking time (0, 20, 40, 60, 80, 100, 120, 150 and 180 minutes), reaction temperature (20→50 °C, 30→60 °C, 40→70 °C, 50→80 °C), the concentration of chitosan (0. 01, 0. 02, 0. 03, 0. 04, 0. 05 g/mL), Fe3O4/chitosan mass ratio (1:1, 1:2, 1:3, 1:4), the amount of glutaraldehyde (8-10 mL), the amount of liquid paraffin (40, 60, 80, 100 mL), and stirring speed (0-2 000 r/min) on the properties of magnetic chitosan microspheres. The morphology, particle size, dispersion, and magnetic responsiveness of magnetic chitosan microspheres were characterized. RESULTS AND CONCLUSION: The optimum conditions for preparing magnetic chitosan microspheres were as follows: Starting with glutaraldehyde as crosslinking agent, the reaction was performed at 40 °C for 1 hour and then at 70 °C for 120 minutes. The concentration of chitosan was 0. 02 g/mL, the mass ratio of Fe3O4/chitosan was 1∶2, the dosage of liquid paraffin was 80 mL, the stirring speed was 1 200 r/min, and the dosage of glutaraldehyde was 8-10 mL. Magnetic chitosan microspheres had strong magnetic properties under the applied magnetic field and had good suspension stability in the natural state. The Fe3O4/chitosan composites were spherical, and the nanoparticles were encapsulated in the microspheres, which were core-shell structure. The surface of the microspheres was smooth and monodisperse. The magnetic chitosan microspheres prepared had a diameter of 1-15 μm, which is beneficial to the dispersion and magnetic separation of the microspheres in the reaction system.

Trace determination and characterization of ginsenosides in rat plasma through magnetic dispersive solid-phase extraction based on core-shell polydopamine-coated magnetic nanoparticles / 药物分析学报

Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80％ after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.

Síntesis y caracterización de nanocompuestos Fe3O4/Ag: su efecto contra Enterobacter aerogenes y Enterococcus faecaiis / Synthesisandcharacterization of nanocompounds Fe3O4/Ag: its effect against Enterobacter aerogenes and Enterococcus faecaiis / Síntese e caracterização de nanocompósitos Fe3O4/Ag: seu efeito contra Enterobacter aerogenes e Enterococcus faecaiis

Resumen En el presente trabajo, se reporta la síntesis y caracterización de nanopartículas magnéticas de magnetita/plata (Fe3O4/Ag) para el estudio de sus propiedades antibacterianas frente a las bacterias Enterobacter aerogenes (Gram-negativa) y Enterococcus faecaiis (Gram-positiva). Las nanopartículas magnéticas de magnetita (MNPs) se sintetizaron por el método de solgel, usando bromuro de cetiltrimetilamonio (CTAB) como surfactante. Posteriormente, en la dispersión coloidal de magnetita, se llevó a cabo la reducción química in situ de iones de plata, usando glucosa como agente reductor y polivinilpirrolidona (PVP) como agente dispersante, para obtener un nanocompuesto magnético Fe3O4/Ag. El análisis morfológico y espectroscópico de las nanopartículas de Fe3O4 y del nanocompuesto de Fe3O4/Ag fue realizado mediante la espectroscopia infrarroja con transformada de Fourier (FTIR), Raman, y Mössbauer (MS), además de la técnica de difracción de rayos X (DRX), la microscopía electrónica de barrido (SEM) y espectroscopia de energía dispersiva de rayos X (EDS). Las nanopartículas de Fe3O4 resultaron esféricas con un diámetro medio de 10 nm y el nanocompuesto de Fe3O4/Ag con un tamaño medio de 28 nm, el test antibacteriano indicó que el uso del nanocompuesto de Fe3O4/Ag a una concentración de 5 mg'mL-1 permite una inhibición total del crecimiento de los microorganismos estudiados a partir de una concentración inicial 108 bacterias mL-1.

Abstract In the present study, we report the synthesis and characterization of magnetite/silver magnetic nanoparticles (Fe3O4/Ag) and the study of their antibacterial properties against the bacteria Enterobacter aerogenes (Gramnegative) and Enterococcus faecaiis (Grampositive). Magnetite magnetic nanoparticles (MNPs) were prepared by a sol-gel method using cetyltrimethylammonium bromide (CTAB), as a surfactant, followed by in-situ chemical reduction of silver ions by glucose, and polyvinylpyrrolidone (PVP), as a dispersive agent, to obtain the antibacterial nanocomposite of Fe3O4/Ag. Morphological and spectroscopic studies of magnetite nanoparticles and nanocomposite were carried out using the Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Mössbauer spectroscopy (MS), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). Spherical Fe3O4 MNPs showed an average diameter of 10 nm and the average size for nanocomposite was 28 nm. The antibacterial test indicated that the use of the nanocomposite of Fe3O4/Ag at a concentration of 5 mg'mL-1 allowed a total inhibition of the growth of the microorganisms studied from an initial concentration of 108 bacteria mL-1.

Resumo No presente trabalho, relatamos a síntese e caracterização de nanopartículas magnéticas de magnetita/prata (Fe3O4/Ag) e o estudo de suas propriedades antibacterianas contra as bactérias Enterobacter aerogenes (Gram-negativo) e Enterococcus faecaiis (Gram-positiva). Nanopartículas magnéticas de magnetita (MNPs) foram sintetizadas pelo método solgel usando o bromuro de cetiltrimetilamonio (CTAB) como surfactante. Posteriormente, na dispersão coloidal de magnetita, a redução química in situ dos íons de prata foi realizada utilizando-se glicose, como agente redutor, e polivinilpirrolidona (PVP), como agente dispersante, para obter um nanocompósito magnético Fe3O4/Ag. A análise morfológica e espectroscópica das nanopartículas de Fe3O4 e do nanocompuesto de Fe3O4/Ag conduziu-se através da espectroscopia infravermelha com transformada de Fourier (FTIR), Raman, e Mössbauer (MS), además da técnica de raio X da deformação (DRX), a microscopia eletrônica de barrido (SEM) e a espectroscopia de energia dispersiva de raios X (EDS). As nanopartículas de Fe O têm formas esféricas com um diâmetro médio de 10 nm e o nanocompósito de Fe3O4/Ag com um tamanho promédio de 28 nm. O teste antibacteriano indicou que o uso do nanocompósito Fe3O4/Ag na concentração de 5 mg'mL-1 permitiu inibir totalmente o crescimento dos microrganismos estudados a partir de uma concentração inicial de 108 bactérias mL-1.

Studies on high-efficiency loading, sustained-release and permeability as transdermal delivery of graphene oxide to docetaxel composites / 中草药

Objective: To synthetize the new-type GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC inclusion compound, and study its high-efficiency loading, sustained-release and permeability as transdermal delivery for docetaxel (DOC) composites. Methods: The concentration of DOC was determined by high efficiency liquid chromatography. The high-efficiency loading, sustained-release and permeability as transdermal delivery of GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were studied, and the encapsulation efficiency and drug loading of them were determined by centrifugation. The GO-DEX-β-CD/DOC and Fe3O4/GO-Na/DOC were applied onto the female mice skin in vitro and in vivo to develop the permeability of them. Results: The encapsulation efficiency and drug loading of Fe3O4/GO-Na/DOC were higher than GO-DEX-β-CD/DOC, and its slow release property and permeability as transdermal delivery were better. The results showed that the accumulation permeation amount was (22.512 ± 0.715) μg after Fe3O4/GO-Na/DOC being applied over 90 h, DOC concentration in skin reached a peak at 15 min by the application of Fe3O4/GO-Na/DOC. After 5 h of administration, DOC concentration in the blood of female mice reached (76.886 ± 1.232) μg/mL. Conclusion: The preparation techniques of Fe3O4/GO-Na/DOC was feasible with better sustained release and transdermal effect, which had a promising application prospect.

Preparation of Adriamycin Hydrochloride Magnetic Thermosensitive Liposome Based on TiO 2@Fe3O4 and Its Physicochemical Properties，Magnetic Effect and Photothermal Effect Study / 中国药房

OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL）， investigate its physicochemical properties， magnetic effect and photothermal effect， so as to provide reference for tumor chemo- therapy and photodynamic/photothermal therapy. METHODS： Using DOX as model drug， TiO2@Fe3O4 as photosensitizers and magnetic materials， DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility were observed； particle size and Zeta potential were detected； encapsulation efficiency of the liposome were determined by centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution， in vitro release behavior of the liposome was investigated by dialysis method， and the release curves at different temperatures （at 37， 43 ℃） were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species （ROS） in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS： Prepared DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion， and was spherical in shape and uniform in size under electron microscopy. Average particle size was 250.6 nm； polydispersity index was 0.107； Zeta potential was （－7.76±3.41）mV； encapsulation efficiency was （92.3±3.2）％. Under the external magnetic field， the liposome could move in a directional direction and had obvious paramagnetism. Compared with DOX solution， the liposomes released slowly and showed obvious sustained- release characteristics. Compared with at 37 ℃， the drug release of liposome speeded up significantly at 43 ℃.With the increase of laser （808 nm） irradiation time， the temperature of the liposome kept rising， which had obvious photothermal conversion effect and could induce the increase of ROS in MCF-7 cells. CONCLUSIONS： DOX-TiO2@Fe3O4-MTSL is prepared succe- ssfully， which has uniform appearance， good physical and chemical properties. It has obvious paramagnetism sustained release effect and photothermal conversion efficiency， and can promote ROS production in MCF-7 cells under near infrared laser irradiation at 808 nm.

Optimization of the formulation of fe3o4 nanoparticles by box-behnken response surface method and its drug release mechanism in vitro / 中国药学杂志

OBJECTIVE: To optimize the formulation of Fe3O4 nanoparticles modified with polyethylene glycol (PEG)through Box-Behnken response surface method.To investigate its release properties in vitro to provide references for the study of drug delivery system. METHODS: Firstly, the formulationof Fe3O4 nanoparticles was optimized by Box-Behnken response surface method. Secondly, the physical and chemical stabilities of Fe3O4 nanoparticles were determined at different stages. Next, doxorubicin hydrochloride, scutellarin and 5-fluorouracil were respectively loaded into Fe3O4 nanoparticles by ultrasonic stirring method and the drug release ability of Fe3O4 nanoparticles was studied by dialysis method. Finally, different mathematical models were applied to fit the release data to explain the release mechanism, and the release ability of Fe3O4 nanoparticles was investigated at different temperatures to clarify the effect of photothermal effect on drug release. RESULTS The particle size of Fe3O4 nanoparticles was from 20 to 30 nm at room temperature. Fe3O4 nanoparticles loading with water-soluble drugs 5-fluorouracil was incompatible with the five models. However, when doxorubicin hydrochloride was loaded, its release fitted well with the Higuchi equation. And both zero-order equation and the Hixson-Crowell equation can match well with such Fe3O4 nanoparticles loading with scutellarin. Finally, it can be clarified with mechanism-verified Ritger-Peppas equation that the simple diffusion motivated the drug release of Fe3O4 nanoparticles loaded with hydrophilic drugs, and the Zero dissolution release mechanism worked when loaded with hydrophobic drugs.As the temperature increases, the release ability of Fe3O4 nanoparticles was increases. CONCLUSION: Hydrophobic drugs can be loaded with SCU in the Fe3O4 nanoparticles by ultrasonic stirring method to improve the biocompatibility of the drugs, which provide some experimental foundation for the research and development of new formulations of poorly soluble drugs.

X-ray diffraction Fourier fingerprint of Farina Ferrum / 中草药

Objective: To establish the Fourier transform X-ray diffraction (XRD) fingerprint of Farina Ferrum and to explore the effect of different processing methods on the quality of medicinal materials. Methods: The technology of powder XRD was used for analyzing Farina Ferrum, and the XRD Fourier fingerprints were also determined. Then the XRD Fourier patterns of six kinds of processed products were compared by superimposed way, and the K value method was used to determine the content of Fe3O4 in different processed products. Results: XRD characteristic fingerprint of 11 batches of Farina Ferrum was established. Ten common peaks were characterized, in which the third and sixth peaks were from Fe3O4 and FeO, respectively. There were some differences in the number and intensity of peaks among raw materials and six kinds of processed products, which were consistent with the variation of mass fraction of Fe3O4. Conclusion: The XRD fingerprint could be used for the appraisal and the analysis of Farina Ferrum, and the basis could be provided for the quality evaluation of Farina Ferrum and the option of processing methods.

Preferential adsorption of flavonoids and organic acids by amino-modified Fe3O4 nanoparticles (MNP-NH2) / 中草药

Objective To synthesize amino-modified Fe3O4 nanoparticles (MNP-NH2) and study the adsorption of flavonoids and organic acids by MNP-NH2. Methods MNP-NH2 were synthesized and characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometer analysis; The adsorption rule of MNP-NH2 was discussed by studying the adsorption properties of 12 monomers. The adsorption properties of MNP-NH2 were assessed under conditions of different ultrasonic time, temperature, ionic strength, and pH. The final elution conditions were determined by L9(34) orthogonal test and the recycling performance was also considered. Results MNP-NH2 synthesized in this study have stable structure, uniform distribution, and good magnetic properties. Adsorption of 12 monomers by MNP-NH2 showed that the mechanism of adsorption was related to the number of ortho-phenolic hydroxyl groups. Ions concentration and temperature had little effect on adsorption for different compounds except pH. The optimized adsorption conditions were extraction for 40 min at 30 ℃ and the final elution conditions were determined to be 5 mL of 20% glacialacetic acid (methanol-water 60∶40) and ultrasonication for 40 min. Conclusion MNP-NH2 can be utilized to extract the effective components of Lonicerae Japonicae Flos and maintain a high adsorption rate of flavonoids. Moreover, MNP-NH2 had great recycling and reproducibility, providing new ideas for the utilization of extracting chemical compounds from complex traditional Chinese medicine and natural medicines.

Facile Synthesis of the Magnetic Metal Organic Framework Fe3O4@UiO-66-NH2 for Separation of Strontium / 生物医学与环境科学（英文）

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr.

Tat-functionalized Ag-FeO nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery

In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed using MCF-7 cells, and using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles, with the IC of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% ID of Tat-FeAgNPs). Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.

Magnetic nanoparticles Fe3O4@PEI induced targeted suicide gene therapy combined with magnetic fluid hyperthermia on hepatoma xenograft / 中国肿瘤生物治疗杂志

@#Objective:To investigate the specific killing effect of magnetic nanoparticles Fe3O4@PEI induced targeted suicide gene therapycombinedwithmagneticfluidhyperthermiaonhepatomaxenograft.Methods:Thesuicidegenetargetinghepatomap[HRE]AFP-HSVTK and tumor cell imaging reporter gene vector p[HRE]AFP-Luc were constructed by sub-cloning gene recombination method, and tested by restriction endonuclease gel electrophoresis. Fe3O4 nano-particles were prepared by co-precipitation method and modified by Polyethyleneimine (PEI) to obtain the magnetic nano-particles Fe3O4@PEI,which could be used as carrier for tumor gene therapy and a medium for magnetic fluid hyperthermia treatment; and the characterization of Fe3O4@PEI was identified by transmission electron microscopy, particle size analyzer and Fourier transform infrared spectroscopy. The reporter genes p[HRE]AFP-Luc were delivered into the nude mice bearing xenografts via tail vein by Fe3O4@PEI, then the bioluminescence signals of mice were observed in an IVIS system.After the treatment of p[HRE]AFP-HSVTK/Fe3O4@PEI, the tumor cell inhibition rate was examined by MTT assay, the cell apoptosis was tested by Flow cytometry, the in vivo tumor development rate and tumor inhibition rate was tested by animal experiment, and the sub-cellular construction of tumor cells was observed by Transmission electron microscopy. Results: Nano-particles Fe3O4@PEI and recombinant vectors p[HRE]AFP-HSVTK and p[HRE]AFP-Luc were successfully constructed; after tale vein injection, image signals were detected only in tumor tissues via IVIS system, but no obvious pathologic damage in other major organs. In the in vitro cell killing test, the cell proliferation inhibition rate and the cell apoptosis rate in combination group was higher than that in hyperthermia treatment group and gene treatment group [inhibition rate: (76.02±7.33)% vs (42.31±4.28)%， (47.76±4.81)%, all P<0.05; apoptosis rate: (34.05±3.41)% vs (14.41±1.55)%， (11.64±1.20)%， all P<0.01]. The in vivo treatment showed that tumor volume development significantly slowed-down and even decreased in combination treatment group, and the tumor mass were significantly smaller than those of the single treatment groups (all P<0.05); and the tumor cell sub- cellular structure showed obvious apoptotic morphology. Conclusion: the suicide gene p [HRE]AFP-HSVTK has specifickillingeffecton hepatomacells,Fe3O4@PEI can be used as effectivegene treatmentcarrierand mediaof magnetic heperthermia treatment; Fe3O4@PEI mediated target treatment combined with magnetic fluid hyperthermia treatment could specificallyinhibitthehepatomaxenograft.

Influence of magnetic Fe3O4 nanoparticles in expressions of Caveolin-1 and Clathrin Heavy Chain proteins in organ tissues of rats / 吉林大学学报(医学版)

Objective:To investigate the influence of magnetic Fe3O4 nanoparticles in the expressions of Caveolin-1 and Clathrin Heavy Chain proteins in organ tissues of the rats, and to clarify its mechanism.Methods:Twenty-four Wistar rats were randomly divided into control group, and low,medium and high doses of magnetic Fe3O4 nanoparticle groups by weights.24 h after tail vein injection of different doses of magnetic Fe3O4 nanoparticles, the organ tissues were obtained.Western blotting method was used to detect the expressions of Caveolin-1 and Clathrin Heavy Chain proteins in the main organ tissues of the rats.Real-time fluorescent quantitative PCR was used to measure the expressions of Caveolin-1 and Clathrin Heavy Chain mRNA.Results:Compared with control group,the expressions levels Clathrin Heavy Chain protein and mRNA in liver and spleen tissues of the rats in medium and high doses groups were significantly increased (P0.05).Compared with control group,the Caveolin-1 mRNA expression levels in liver, spleen, and lung tissues of the rats in low,medium and high doses groups were significantly increased (P0.05).Conclusion:Magnetic Fe3O4 nanoparticles could enhance the expressions of Clathrin Heavy Chain in the liver, spleen, and lung tissues of the rats.Endocytosis of Clathrin Heavy Chain protein is one way for magnetic Fe3O4 nanoparticles into the liver, lung, spleen cells of the rats.

Combined Toxicity of an Environmental Remediation Residue, Magnetite Fe3O4 Nanoparticles/Cr(VI) Adduct / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This paper aims to elucidate the combined toxicity of magnetite nanoparticles/Chromium [MNPs/Cr(VI)] adducts.</p><p><b>METHODS</b>The HEK293 cell was exposed to either Cr(VI) or MNPs, or their adducts MNPs/Cr(VI). The cytotoxicity was evaluated by assessing the cell viability, apoptosis, oxidative stress induction, and cellular uptake.</p><p><b>RESULTS</b>The toxicity of formed adducts is significantly reduced when compared to Cr(VI) anions. We found that the cellular uptake of MNPs/Cr(VI) adduct was rare, only few particles were endocytosed from the extracellular fluid and not accumulated in the cell nucleus. On the other hand, the Cr(VI) anions entered cells, generated oxidative stress, induced cell apoptosis, and caused cytotoxicity.</p><p><b>CONCLUSION</b>The results showed minor effects of the nanoadducts on the tested cells and supported that magnetite nanoparticles could be implemented in the wastewater treatment process in which advantageous properties outweigh the risks.</p>

Tumor Targeting of Fluorescent Magnetic IR780-Fe3 O4 Nanoparticles for Detection of Circulating Tumor Cells / 分析化学

The tumor targeted fluorescent magnetic IR780-Fe3 O4 nanoparticles were prepared for separation and detection of circulating tumor cells ( CTCs ) . These IR780-Fe3 O4 nanoparticles were characterized by electron microscopy, fluorescence spectrometer, and superconducting quantum interferometer. The targeting effect of IR780-Fe3 O4 nanoparticles was analyzed on the tumor and normal cells by confocal microscope and flow cytometry, and the confocal microscope was used to target the location of IR780-Fe3 O4 nanoparticles in MCF-7 cells. The standard curve was drawn and evaluated accorded to the IR780-Fe3 O4 nanoparticles fluorescence intensity of tumor cells after incubation. The results showed that IR780-Fe3 O4 nanoparticles could target a variety of CTCs. Furthermore, cellular localization experiment proved that IR780-Fe3 O4 nanoparticles could target the mitochondria of tumor cells. With the method of coupling magnetic Fe3 O4 nanoparticles, IR780 could well distinguish the tumor and normal cells, which could be used for separating and detecting the CTCs in simulated blood.

Tumor Targeting of Fluorescent Magnetic IR780-Fe3 O4 Nanoparticles for Detection of Circulating Tumor Cells / 分析化学

The tumor targeted fluorescent magnetic IR780-Fe3 O4 nanoparticles were prepared for separation and detection of circulating tumor cells ( CTCs ) . These IR780-Fe3 O4 nanoparticles were characterized by electron microscopy, fluorescence spectrometer, and superconducting quantum interferometer. The targeting effect of IR780-Fe3 O4 nanoparticles was analyzed on the tumor and normal cells by confocal microscope and flow cytometry, and the confocal microscope was used to target the location of IR780-Fe3 O4 nanoparticles in MCF-7 cells. The standard curve was drawn and evaluated accorded to the IR780-Fe3 O4 nanoparticles fluorescence intensity of tumor cells after incubation. The results showed that IR780-Fe3 O4 nanoparticles could target a variety of CTCs. Furthermore, cellular localization experiment proved that IR780-Fe3 O4 nanoparticles could target the mitochondria of tumor cells. With the method of coupling magnetic Fe3 O4 nanoparticles, IR780 could well distinguish the tumor and normal cells, which could be used for separating and detecting the CTCs in simulated blood.

Preparation of doxorubicin-loaded Fe3O4-TiO2 nanoparticles and evaluation of chemo-photodynamic therapy in vivo / 药学学报

Magnetic iron oxide (Fe3O4) nanoparticles were sythesized using solvothermal reaction and then coated with titanium oxide (TiO2) via sol-gel process of hydrolysis and condensation of tetrabutyl titanate (TBOT). The obtained Fe3O4-TiO2 particles were characterized with transmission electron microscope (TEM) and dynamic light scattering (DLS). The loading and release of doxorubicin (DOX) were evaluated. Methyl thiazolyl tetrazolium (MTT) method was used to study the cytotoxicity and effect of chemo-photodynamic therapy. The obtained Fe3O4-TiO2 particles were uniform and well dispersed. The loading capacity of DOX was 43%. A pH-sensitive release property of Fe3O4-TiO2-DOX was observed. In the cytotoxicity experiment, cytotoxicity was found upon combination of Fe3O4-TiO2-DOX and ultraviolet (UV), while no obvious cytotoxicity was found in the blank Fe3O4-TiO2 particles. In conclusion, the fabricated Fe3O4-TiO2 nanoparticles exhibited a high loading capacity and excellent photodynamic therapeutic effect, suggesting that it may be used as a novel carrier for chemo-photodynamic therapy of cancer.

Fluorescent Detection of Specific DNA Sequences Related to Toxoplasma gondii Based on Magnetic Fluorescent Nanoparticles Fe3O4/CdTe Biosensor.

Magnetic fluorescent nanoparticles (Fe3O4/CdTe) were prepared in this work and applied for Toxoplasma gondii DNA detection. First, CdTe quantum dots were synthesized with 3- mercaptopropionic (MPA) capped. Fe3O4 magnetic particles were prepared by hydrothermal method with NaOH as precipitator, and they were surfacely modified with silane coupling agent (KH550). After then, the MPA-capped CdTe QDs were immobilized on the Fe3O4 particles surface via electrostatic interaction, and the Fe3O4/CdTe particles were prepared with the average size of 10 nm. The DNA sensing probe was fabricated through labeling a stem-loop Toxoplasma gondii DNA oligonucleotides with Fe3O4/CdTe (donor) at the 5′ end and BHQ2 (acceptor) at 3′ end, respectively. The assembly prosess was verified by UV-Vis, TEM, IR, XRD etc. The sensitivity characterization of the molecular beacon probe was performed by fluorescence spectrum (FS) with a detection limit of 8.339x10-9M. This chemical strategy can be further applied to prepare the magnetic nanoparticles for DNA detection.