Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Preparation and polarization activity research of astragalus polysaccharide-superparamagnetic iron oxide nanocomposite / 药学学报

Size and surface modification are the two key factors affecting the effect of macrophages polarization induced by superparamagnetic iron oxide nanoparticles (SPIONs). The smaller the particle size, the better the polarization effect of SPIONs. Besides, the reasonable SPIONs surface modification method can also be used to enhance the polarization effect. In this study, SPIONs was prepared by solvothermal method and optimized by Box-Benhnken center combination design and response surface method. Furthermore, astragalus polysaccharide-superparamagnetic iron oxide nanocomplex (APS-SPIONs) was successfully constructed by EDC/NHS esterification method. The structure of APS-SPIONs was confirmed by dynamic light scatter and infrared spectrometer, and the contents of iron and polysaccharide were characterized by spectrophotometry. The effect of APS-SPIONs on inducing mouse macrophages RAW264.7 polarization was investigated by flow cytometry. The RAW264.7 macrophages-HepG2 human hepatoma cancer cells Transwell co-culture system was established to investigate APS-SPIONs improve anti-tumor function of macrophages in vitro, and the proliferation activity of APS-SPIONs on RAW264.7 detected by cell counting kit-8 (CCK-8) method. The results showed that the average particle size and zeta potential of APS-SPIONs were (82.93 ± 1.47) nm and (-24.00 ± 0.47) mV. Polysaccharide and Fe content were 8.69% and 7.04%, respectively. APS-SPIONs effectively induced the polarization of RAW264.7 into M1 type in vitro, improving the anti-tumor ability of macrophages in a co-culture system, without effecting the proliferation of macrophages. Our study provides a drug development strategy and preliminary research results to educate macrophages and reshape the tumor immune microenvironment to achieve tumor-killing effects.

Research progress on the effect of iron oxide nanoparticles in macrophage polarization / 生物医学工程学杂志

Macrophages are important immune effector cells with significant plasticity and heterogeneity in the body immune system, and play an important role in normal physiological conditions and in the process of inflammation. It has been found that macrophage polarization involves a variety of cytokines and is a key link in immune regulation. Targeting macrophages by nanoparticles has a certain impact on the occurrence and development of a variety of diseases. Due to its characteristics, iron oxide nanoparticles have been used as the medium and carrier for cancer diagnosis and treatment, making full use of the special microenvironment of tumors to actively or passively aggregate drugs in tumor tissues, which has a good application prospect. However, the specific regulatory mechanism of reprogramming macrophages using iron oxide nanoparticles remains to be further explored. In this paper, the classification, polarization effect and metabolic mechanism of macrophages were firstly described. Secondly, the application of iron oxide nanoparticles and the induction of macrophage reprogramming were reviewed. Finally, the research prospect and difficulties and challenges of iron oxide nanoparticles were discussed to provide basic data and theoretical support for further research on the mechanism of the polarization effect of nanoparticles on macrophages.

The curative effect and mechanism of magnetic hyperthermia in the treatment of knee osteoarthritis / 西安交通大学学报(医学版)

【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.

Green synthesis and characterization of iron oxide nanoparticles using Coriandrum sativum L. leaf extract

Green nanoparticle synthesis is a promising, eco-friendly and safe approach. In the current study, Iron oxide nanoparticles (FeONPs) were synthesized using aqueous leaf extract of Coriandrum sativum L. Further, the characterization of synthesized FeONPs was performed using ultraviolet-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and differential scanning colorimetry (DSC). The surface plasmon resonance effect confirmed the synthesis of FeONPs. Dynamic light scattering (DLS) revealed mean particle size of FeONPs around 163.5 and polydispersity index 0.091 with a zeta potential of ?13.8 mV. Differential scanning colorimetry (DSC) exhibited an endothermic peak at 176.91°C. Vibrating sample magnetometer (VSM) analysis showed superparamagnetic properties of iron nanoparticles with a magnetization value of 3.483 emu/g and the results indicated superparamagnetic behavior of prepared iron nanoparticles at room temperature, thus highlighting their potential as magnetically targeted drug delivery system. This biosynthetic method has been proven to be cost-effective, environment friendly and promising for use in biomedical sciences.

Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.

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.

Effects of Fluorodeoxyglucose Conjugated and Unconjugated Iron Oxide Magnetic Nanoparticles on Macrophages: a Pilot Study

Abstract The effects of fluorodeoxyglucose conjugated iron oxide magnetic nanoparticles (FDGMNP) on macrophages are presented using a yeast substrate. Iron oxide magnetic nanoparticles (MNP) were synthesized by partially reducing FeCl3, then conjugated with (3-aminopropyl) triethoxysilane (APTES) after silication with tetraethyl orthosilicate. Silanated MMP nanoparticles were combined with fluorodeoxyglucose (FDG). Fluorodeoxyglucose iron oxide magnetic nanoparticles (FDGMNP) and its unconjugated control (MNP) were added (1mL) to the cells from the murine macrophage-like, Abelson murine leukemia virus transformed cell line RAW 264.7 (American Type Culture Collection number TIB-71) cell culture wells at different concentrations from 90-3.6 μg/mL. Cells were placed on the magnet plate for 30 min before incubating at 37°C, 5% CO2 overnight. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium) assay was performed to measure cell viability. Our results demonstrate that iron based nanoparticles can be linked to macrophages (elements of the immune system that attack bacteria) without the function of the macrophages being affected, ie no detrimental effects to the macrophages were evident in these experiments. We conclude that neither FDGMNP nor MNP had a detrimental effect on macrophage function.

Simarouba Glauca Bark Extract Mediated Synthesis And Characterisation Of Iron Oxide And Silver Nanoparticles And Their Antibacterial, Cytotoxic And Photocatalytic Activity

Objective: The objective of the present study is the synthesis of iron oxide and silver nanoparticles using Simarouba glauca aqueous bark extract, characterization of the synthesized nanoparticles and evaluation of their antimicrobial, photocatalytic activity and cytotoxicity. Methods: The iron oxide and silver nanoparticles were synthesized using Simarouba glauca aqueous bark extract and crystal structures of the nanoparticles were determined by UV-Visible spectroscopy, Transmission Electron Microscopy, Scanning Electron Microscopy, X-ray Diffraction and Fourier Transform Infrared Spectroscopy. The in vitro cytotoxicity of the silver nanoparticles was evaluated using Dalton’s lymphoma ascites cells. The antibacterial assay of the silver nanoparticles was conducted using agar well diffusion method. Results: The UV-Visible spectrum of iron oxide nanoparticle showed an absorption maximum at 280 nm and silver nanoparticles showed an absorption maximum at 436 nm. This is XRD pattern of iron oxide nanoparticles exhibited a characteristic peak at 26.85 is of maghemite the corresponding miller indices is (211) and the synthesized iron oxide nanoparticles are amorphous in nature. TEM image reveals the size of the synthesized iron oxide nanoparticles in the range of 26-30 nm and the size of silver nanoparticles is in the range of 120-140 nm. Green synthesized iron nanoparticles using Simarouba glauca bark extract effectively degraded methylene blue dye. Conclusion: This study showed that the synthesized iron oxide and silver nanoparticles using Simarouba glauca aqueous bark extract exhibited pronounced antibacterial, anticancer and photocatalytic activity and can be used in the textile industry and also as an external antiseptic in prevention and treatment of bacterial infections.

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.

The Impact of IONPs and PBNPs Nanoparticles in Regulating Stemness of Ovarian Carcinoma Cells / 中国药学杂志

OBJECTIVE: To study the effects of iron oxide nanoparticles (IONPs) and prussian blue nanoparticles (PBNPs) on the stemness of epithelial ovarian cancer (EOC) cell lines, which may provide experimental basis and reference significance for the application of nanoparticles in the treatment of EOC. METHODS: SKOV3 and HO8910 cell lines were treated with IONPs and PBNPs respectively, then the drug-resistant genes in mRNA and protein levels were detected by RT-PCR and Western blot. The change of cell proliferation ability were detected by cell proliferation and clone formation experiments, and the expression of surface stemness-related molecules were detected by flow cytometer. RESULTS: The expression of ABCG2 and ALDH1A1 were both down regulated in SKOV3 and HO8910 cell lines treated with IONPs and PBNPs, respectively, while IONPs decreased the CD44+CD117+ subpopulation, and PBNPs increased the CD44+CD117+ subpopulation. Compared with the control cells, the proliferation of SKOV3 cells treated with IONPs and PBNPs were significantly reduced, however, there were no effects on HO8910 cell's proliferation after the cells treated with PBNPs. CONCLUSION: Drug-resistance genes and stem cell subpopulation of EOC SKOV3/HO8910 cell lines treated with IONPs were markedly reduced. However, PBNPs can improve the stem cell subpopulation and promote the cancer stem cell's characteristic of EOC cells but the drug-resistance genes were decreased.

Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams

Purpose: Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams. Materials and Methods: In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay. Results: Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations. Conclusion: Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy

Anti-Diabetic, Anti-Cancer Activity And Associated Toxicity Of Leucas Aspera Extract In Wistar Albino Rats

In regenerative medicine, nanotechnology plays a vital role in the diagnosis, the delivery of therapeutic drugs and the treatment of many diseases and disorders. Due to the growing need to develop environmentally friendly technologies in material synthesis, the biosynthesis of Iron Oxide Nanoparticles (IOP) has received considerable attention over the past decades. Therefore, the community is now looking back for traditional medicines for various diseases after the practice of allopathic drugs with tremendous side effects. There are an increasing number of biomedical applications for iron oxide nanoparticles; as such uses are essential for in-vitro characterisation and in-vivo to ensure the bio-safety of these particles. The main complication of diabetes due to frequent lipid peroxidation is liver damage and renal dysfunction, but treatment with Leucas aspera has a pronounced effect on these indicators, which protects the organs from further damage. The current research supports the traditional use of Leucas aspera against diabetes mellitus and cancer, as well as the safety, effectiveness and potency of Leucas aspera leaf extract's anti-diabetic and anti-cancer effect in the in-vivo model. The overall results reveal that Leucas aspera has the potential and can be a candidate of choice without side effect.

Multimodal Composite Iron Oxide Nanoparticles for Biomedical Applications

BACKGROUND: Iron oxide nanoparticles (IONPs) are excellent candidates for biomedical imaging because of unique characteristics like enhanced colloidal stability and excellent in vivo biocompatibility. Over the last decade, material scientists have developed IONPs with better imaging and enhanced optical absorbance properties by tuning their sizes, shape, phases, and surface characterizations. Since IONPs could be detected with magnetic resonance imaging, various attempts have been made to combine other imaging modalities, thereby creating a high-resolution imaging platform. Composite IONPs (CIONPs) comprising IONP cores with polymeric or inorganic coatings have recently been documented as a promising modality for therapeutic applications. METHODS: In this review, we provide an overview of the recent advances in CIONPs for multimodal imaging and focus on the therapeutic applications of CIONPs. RESULTS: CIONPs with phototherapeutics, IONP-based nanoparticles are used for theranostic application via imaging guided photothermal therapy. CONCLUSION: CIONP-based nanoparticles are known for theranostic application, longstanding effects of composite NPs in in vivo systems should also be studied. Once such issues are fixed, multifunctional CIONP-based applications can be extended for theranostics of diverse medical diseases in the future.

Application of iron oxide magnetic nanoparticles in tumor theranostics / 中国药科大学学报

@#With the rapid development of nanotechnology, accurate personalized treatments for tumor have attracted more attention to increase the therapeutic effects and reduce the side effects. The emerging theranostic systems incorporating different therapeutic and diagnostic imaging capabilities have become a new research hotspot. Magnetic iron oxide nanoparticles(IONP)have been widely used in theranostic systems due to their unique imaging properties, stable thermal performance, excellent biocompatibility and admirable surface modifiability. In this review, we analyzed the advantages of IONP in the diagnosis and the treatment of tumor, and detailedly introduced the relevant strategies and latest research progress, including magnetic resonance imaging(MRI), photothermal therapy, magnetic hyperthermia, and magnetic targeted drug delivery, etc. Finally, the potential application of IONP in the clinical tumor theranostics was proposed.

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.

Preparation of MRI contrast of dual-targeted cell adhesion molecules with microparticles of iron oxide and in vitro experiment / 中国医学影像技术

Objective: To evaluate the specificity and efficacy of combination of dual-targeted MRI contrast agent cell adhesion molecule (CAM)-microparticles of iron oxide (MPIO) and endothelial cells. Methods: The single-targeted contrast agent intercellular adhesion molecule (ICAM)-MPIO, vascular cell adhesion molecule (VCAM)-MPIO and dual-targeted contrast agent CAM-MPIO were synthesized, then Prussian blue staining, immunofluorescence and MR scanning were applied to estimate the specificity and efficacy of combination of contrast agents and tumor necrosis factor-α (TNF-α) activated endothelial cells. Results: Prussian blue staining showed much stronger blue granules surrounding the stimulated cells in CAM-MPIO group than in ICAM-MPIO group and VCAM-MPIO group. Immunofluorescence essay demonstrated that the yellow fluorescence area per cell of CAM-MPIO group was (2.00±0.31) times and (2.46±0.45) times higher than that of ICAM-MPIO group and VCAM-MPIO group. In vitro MRI showed the signal intensity of T2WI and T2 value decreased with the increase concentration of targeted contrast agents, especially in CAM-MPIO group. Conclusion: Dual-targeted probe CAM-MPIO may be more valuable than single-targeted probe ICAM-MPIO and VCAM-MPIO for imaging diagnosis of early radiation-induced brain injury.

Advances in the application of iron oxide based magnetic nanoparticles in cancer ther-anostics / 中国肿瘤临床

Cancer theranostics has attracted increasing attention in the area of nanooncology, where the therapeutic drugs and diag-nostic imaging are integrated into a multifunctional nanoplatform. A theranostic nanoparticle can deliver therapeutic drugs and imag-ing agents simultaneously. Iron oxide based magnetic nanoparticles (MNPs) are one of the most typical theranostic nanoparticles and have many excellent properties, such as biosafety, superparamagnetism, and tunable surface modifications and functionalizations. Moreover, they have drug loading capacity along with the distinctive properties of T2 weighted magnetic resonance imaging (T2W MRI), magnetic targeting, and magnetic hyperthermia. Presently, iron oxide based MNPs are being widely used in cancer theranostic research. This paper introduces the general structure of iron oxide based MNPs and reviews their applications in cancer dual/multiple modal imaging (T2W MRI combining T1W MRI, CT, optical imaging, PET/SPECT, and ultrasound) and therapy (chemotherapy, photody-namic therapy, photothermal therapy, and magnetic hyperthermia).