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双重包裹于交联角叉菜胶/聚乙二醇化羧甲基纤维素中的磁性纳米颗粒;一种用于阿霉素pH触发释放的生物相容性纳米载体。

Magnetic nanoparticles double wrapped into cross-linked salep/PEGylated carboxymethyl cellulose; a biocompatible nanocarrier for pH-triggered release of doxorubicin.

作者信息

Hosseini Seyed Hassan, Zohreh Nasrin, Karimi Nafiseh, Gaeini Nahid, Alipour Sakineh, Seidi Farzad, Gholipour Nazila

机构信息

Department of Chemical Engineering, University of Science and Technology of Mazandaran, Behshahr, Iran.

Department of Chemistry, Faculty of Science, University of Qom, Qom, Iran.

出版信息

Int J Biol Macromol. 2020 May 8;158:994-1006. doi: 10.1016/j.ijbiomac.2020.05.040.

DOI:10.1016/j.ijbiomac.2020.05.040
PMID:32434748
Abstract

A magnetic nanocarrier was synthesized in which FeO nanoparticles were encapsulated into double layers of polysaccharide shells. The first shell, which was composed of cross-linked salep polysaccharide, contained multiple nitrogen atoms in its structure and provided numerous sites for multiple functionalization. A fluorescence dye and doxorubicin, as widely used chemotherapy agent, were easily attached to the first shell and then a second shell of PEGylated carboxymethyl cellulose enveloped the drug loaded carrier to enhance its biocompatibility and regulates the drug release behavior. The results of drug loading and release behavior showed that the resulting nanocarrier can carry large amounts of drug molecules and a remarkable pH-sensitive release was observed in vitro. The hemolysis and coagulation assays proved the biocompatibility of nanocarrier toward red blood cells and the MTT experiments confirmed that the drug loaded nanocarrier is highly toxic for MCF-7 cancer cells while the unloaded nanocarrier was almost nontoxic. Further flow cytometry experiments and confocal microscopy demonstrated that the double layered magnetic nanocarrier can penetrate into the cells and efficiently release the drug molecules into the cell nucleus. Moreover, the results of MRI experiments performed on the nanocarrier showed that it can be serve as a negative MRI contrast agent.

摘要

合成了一种磁性纳米载体,其中FeO纳米颗粒被包裹在多糖壳的双层结构中。第一层壳由交联的萨雷普多糖组成,其结构中含有多个氮原子,并为多种功能化提供了大量位点。一种荧光染料和作为广泛使用的化疗药物的阿霉素很容易附着在第一层壳上,然后聚乙二醇化羧甲基纤维素的第二层壳包裹了载药载体,以增强其生物相容性并调节药物释放行为。药物负载和释放行为的结果表明,所得纳米载体可以携带大量药物分子,并且在体外观察到显著的pH敏感释放。溶血和凝血试验证明了纳米载体对红细胞的生物相容性,MTT实验证实载药纳米载体对MCF-7癌细胞具有高毒性,而未载药的纳米载体几乎无毒。进一步的流式细胞术实验和共聚焦显微镜表明,双层磁性纳米载体可以穿透细胞并将药物分子有效释放到细胞核中。此外,对纳米载体进行的MRI实验结果表明,它可以用作阴性MRI造影剂。

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