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Polyvinylpyrrolidone Loaded-MnZnFe 2 O 4 Magnetic Nanocomposites Induce Apoptosis in Cancer Cells Through Mitochondrial Damage and P 53 Pathway
Journal of Inorganic and Organometallic Polymers and Materials ( IF 4 ) Pub Date : 2020-07-03 , DOI: 10.1007/s10904-020-01651-1
Sahira Hassan Kareem , Amel Muhson Naji , Zainab J. Taqi , Majid S. Jabir

MnZnFe2O4 ferrite was successfully synthesized using metallic chlorides and polyvinylpyrolidone, by Co-precipitate method. Deferent concentrations of PVP (0.1, 0.3, 0.5, 0.7, and 0.9) wt%, were used as capping agent to stabilize the particles and prevent them from agglomeration. The PVP content had a vital influence on enhancing the properties of the ferrite nanoparticles. From X-ray data the degree of crystallinity and the Lattice constants (a) of the nanoparticles increased from (8.92 nm) and (8.344 Å) to (19.94 nm) and (8.395 Å) respectively with increasing PVP concentrations. The morphology and average particle size of the MnZn ferrite nanoparticles were evaluated by scanning electron microscopy (SEM), the values were in a good agreement with the XRD results. Fourier transform infrared spectroscopy (FT-IR) confirmed the cubic structure with octahedral and tetrahedral, also indicated the formation of bond between PVP and surface of metallic hydroxide of ferrite nanoparticles. Vibrating sample magnetometer (VSM) analysis was performed for all samples at room temperature, results showed that the specimens exhibited a paramagnetic behavior in the absence of PVP while in the presence of PVP they have super paramagnetic characteristics. The values of saturation magnetization (Ms) (1.78–17.67 emu/g), remnant magnetization (Mr) (0.0022–0.0696 emu/g) also increased with increasing pvp concentration. Polyvinylpyrrolidone loaded-MnZnFe2O4 magnetic nanocomposites were used it alone or as a combination therapy with NIR laser, and alternating magnetic field (AMF) as anti-proliferative agent against breast cancer cell lines AMJ-13, MCF-7,and ovarian cancer cell line SKOV-3 as well as against normal cell line HBL. While, its capability to induce apoptosis was detected using different techniques which is acridine orange/ethidium bromide (AO/EtBr) staining and mitochondrial membrane potential (MMP), and flow cytometry assay membrane potential (MMP). q-PCR was used to investigate the changes in the expression of P53 gene. The influence of Polyvinylpyrrolidone loaded-MnZnFe2O4 magnetic nanocomposites in viability of breast and ovarian cancer cells alone or when they used as a combination therapy with laser photo-thermal therapy and alternating magnetic field (AMF) was also tested using MTT assay. Our results in the present study demonstrated that the inhibition activity of Polyvinylpyrrolidone loaded-MnZnFe2O4 magnetic nanocomposites against treated cancer cell lines increased when Polyvinylpyrrolidone loaded-MnZnFe2O4 nanocomposites used with NIR laser, while highly increased cytotoxic activities were observed after exposure of Polyvinylpyrrolidone loaded-MnZnFe2O4 nanocomposites to induction heating with AMF. Treated cancer cells with polyvinylpyrrolidone loaded-MnZnFe2O4 magnetic nanocomposites significantly increased ROS synthesis, with subsequent reduction of the MMP. The results of the current study show that tested compounds suppressed cancers cells’ proliferation and has a growth inhibitory effect on different cancer cells, resulting in apoptosis as a novel pathway that involves mitochondrial damage mechanism via activated P53. Taken together the present data suggest that the Polyvinylpyrrolidone loaded-MnZnFe2O4 magnetic nanocomposites could be promising therapy protocol for cancer cells.



中文翻译:

聚乙烯吡咯烷酮负载的MnZnFe 2 O 4磁性纳米复合材料通过线粒体损伤和P 53途径诱导癌细胞凋亡。

锰锌铁2 O 4用金属氯化物和聚乙烯吡咯烷酮通过共沉淀法成功合成了铁氧体。将不同浓度的PVP(0.1、0.3、0.5、0.7和0.9)wt%用作封端剂,以稳定颗粒并防止其结块。PVP含量对增强铁氧体纳米颗粒的性能具有至关重要的影响。根据X射线数据,随着PVP浓度的增加,纳米颗粒的结晶度和晶格常数(a)从(8.92 nm)和(8.344Å)分别增加到(19.94 nm)和(8.395Å)。MnZn铁氧体纳米粒子的形貌和平均粒径通过扫描电子显微镜(SEM)进行了评价,其值与XRD结果吻合良好。傅立叶变换红外光谱(FT-IR)证实了八面体和四面体的立方结构,也表明PVP与铁氧体纳米粒子的金属氢氧化物表面之间形成了键。在室温下对所有样品进行振动样品磁力计(VSM)分析,结果表明,在不存在PVP的情况下,样品表现出顺磁性能,而在存在PVP的情况下,它们具有超顺磁特性。饱和磁化强度(Ms)(1.78–17.67 emu / g),剩余磁化强度(M 结果表明,在不存在PVP的情况下,样品表现出顺磁性能,而在存在PVP的情况下,它们具有超顺磁特性。饱和磁化强度(Ms)(1.78–17.67 emu / g),剩余磁化强度(M 结果表明,在不存在PVP的情况下,样品表现出顺磁特性;而在存在PVP的情况下,它们具有超顺磁特性。饱和磁化强度(Ms)(1.78–17.67 emu / g),剩余磁化强度(Mr)(0.0022–0.0696 emu / g)也随着pvp浓度的增加而增加。聚乙烯吡咯烷酮负载的MnZnFe 2 O 4磁性纳米复合材料可单独使用或与NIR激光组合使用,并以交变磁场(AMF)作为抗增殖剂对抗乳腺癌细胞系AMJ-13,MCF-7和卵巢癌细胞系SKOV-3以及针对正常细胞系HBL的细胞系。同时,使用不同的技术检测了其诱导凋亡的能力,这是is啶橙/溴化乙锭(AO / EtBr)染色和线粒体膜电位(MMP),以及流式细胞仪测定膜电位(MMP)。使用q-PCR研究P53基因表达的变化。聚乙烯吡咯烷酮-MnZnFe 2 O的影响还使用MTT分析法测试了4种磁性纳米复合材料在乳腺癌和卵巢癌细胞中的生存力,或将其与激光光热疗法和交变磁场(AMF)联合使用时的生存力。我们在本研究结果表明,聚乙烯基吡咯烷酮的抑制活性加载-MnZnFe 2 ö 4对处理过的癌细胞系磁性纳米复合材料时增加聚乙烯吡咯烷酮装入-MnZnFe 2层ö 4用NIR激光器中使用的纳米复合材料,而高度增加的曝光后观察到细胞毒活性聚乙烯吡咯烷酮-MnZnFe 2 O 4的合成纳米复合材料用于AMF感应加热。用聚乙烯吡咯烷酮负载的MnZnFe 2 O 4磁性纳米复合材料处理的癌细胞显着增加了ROS的合成,并随后降低了MMP。目前的研究结果表明,所测试的化合物抑制癌细胞的增殖,并对不同的癌细胞具有生长抑制作用,从而导致凋亡,这是一条通过激活的P53参与线粒体损伤机制的新​​途径。综上所述,目前的数据表明负载聚乙烯吡咯烷酮的MnZnFe 2 O 4磁性纳米复合材料可能是有前途的癌细胞治疗方案。

更新日期:2020-07-03
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