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基于分子印迹技术的理性设计磁性药物载体提高叠氮胸苷对乳腺癌的抗癌活性。

Increasing the anticancer activity of azidothymidine toward the breast cancer via rational design of magnetic drug carrier based on molecular imprinting technology.

机构信息

Department of Chemistry, Razi University, Kermanshah 67149-67346, Iran.

Department of Chemistry, Razi University, Kermanshah 67149-67346, Iran.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109771. doi: 10.1016/j.msec.2019.109771. Epub 2019 May 21.

Abstract

Cancer treatment based anticancer drugs face serious obstacles. To prevail these obstacles, an effective targeted drug carrier can be imperative. This study aimed to design rationally an imprinting strategy for the carrying of a model anticancer drug, Azidothymidine via molecular imprinting technology. Considering the identity and affinity of monomers and cross-linkers to AZT, this work succeeded to establish an exclusive procedure to significantly improve the process of imprinting the Azidothymidine. Imprinting process was carried out on the surface of vinyl-modified silica coated FeO nanoparticles toward the delivery of azidothymidine to targeted tissue by external magnetic field. The resultant carrier was characterized by FT-IR, XRD, VSM, FESEM, EDX, BET, TGA. The AZT loading process on the nanocarrier is followed with Freundlich adsorption isotherm (Q:170 mg/g) and pseudo-second order fast adsorption kinetic (5 min). The release process of AZT from nanocarrier was fitted with First-Order and Higuchi dynamic model. Eventually, the involvement of magnetic nanocarrier was investigated on apoptosis in MCF-7 (cancer cell line) and MCF-10 (normal cell line). The cytotoxicity percentage on MCF-7 cells for magnetic nanocarrier was about 49 times greater than the azidothymidine, but did not affect MCF-10 cells. The corresponding results appropriately disclosed that the cytotoxicity of proposed nanocarrier on MCF-7 cells is through the caspase3 activity. The drug loading and release process as well as in-vitro studies of magnetic carrier were compared with bare carrier. This study indicates that the proposed magnetic carrier can be used as a promising drug carrier toward the breast cancer treatment.

摘要

基于抗癌药物的癌症治疗面临严重障碍。为了克服这些障碍,一种有效的靶向药物载体是必不可少的。本研究旨在通过分子印迹技术设计一种用于携带模型抗癌药物阿扎胞苷的印迹策略。考虑到单体和交联剂与 AZT 的同一性和亲和力,本工作成功建立了一种独特的程序,可显著改善印迹阿扎胞苷的过程。印迹过程在乙烯基改性的硅胶涂覆的 FeO 纳米粒子的表面上进行,通过外部磁场将阿扎胞苷递送到靶向组织。所得载体通过 FT-IR、XRD、VSM、FESEM、EDX、BET、TGA 进行了表征。纳米载体上的 AZT 加载过程遵循 Freundlich 吸附等温线(Q:170mg/g)和准二级快速吸附动力学(5min)。AZT 从纳米载体的释放过程拟合为一级和 Higuchi 动力学模型。最后,研究了磁性纳米载体对 MCF-7(癌细胞系)和 MCF-10(正常细胞系)细胞凋亡的影响。磁性纳米载体对 MCF-7 细胞的细胞毒性百分比比阿扎胞苷高约 49 倍,但对 MCF-10 细胞没有影响。相应的结果表明,所提出的纳米载体对 MCF-7 细胞的细胞毒性是通过 caspase3 活性实现的。对磁性载体的药物负载和释放过程以及体外研究与裸载体进行了比较。本研究表明,所提出的磁性载体可作为一种有前途的药物载体,用于治疗乳腺癌。

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