Zakerzadeh Elham, Salehi Roya, Mahkam Mehrdad
a Chemistry Department , Azarbaijan Shahid Madani University , Tabriz , Iran.
b Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Science , Tabriz University of Medical Sciences , Tabriz , Iran.
Drug Dev Ind Pharm. 2017 Dec;43(12):1963-1977. doi: 10.1080/03639045.2017.1357730. Epub 2017 Aug 3.
Due to multidrug resistance of cancer tissues and immune-suppression of cancerous patients during chemotherapy in one hand and the use of tetrazole derivatives in medicine because of its anticancer, antifungal, and antiviral properties, on the other, we were encouraged to design novel smart antibacterial nanocomposites-based polymer of tetrazole as dual anticancer drug delivery systems. The structures of nanocomposites characterized by FTIR, H NMR, FESEM-EDX, and TGA analyzes and antibacterial activity of smart carriers were evaluated by determination of minimum inhibitory concentration (MIC) values against some bacteria and fungi. Then, the pH-responsive manner of both nanocomposites was proved by checking their release profiles at pH of the physiological environment (pH 7.4) and pH of tumor tissues (mildly acidic). Finally, the potential antitumoral activity of these nanocomposite systems against MCF7 cell lines was evaluated by MTT assay and cell cycle studies. The results demonstrated that the novel developed nanocomposites not only meet our expectations about simultaneous release of two anticancer drugs according to the predicted profile but also showed antibacterial and anticancer properties in vitro experimental. Moreover, it was proved that these carriers have tremendous potential in multifunctional drug delivery in cancer therapy.
一方面，由于癌症组织的多药耐药性以及癌症患者在化疗期间的免疫抑制，另一方面，由于四唑衍生物具有抗癌、抗真菌和抗病毒特性而在医学上得到应用，我们受到鼓舞去设计基于四唑的新型智能抗菌纳米复合材料聚合物作为双重抗癌药物递送系统。通过傅里叶变换红外光谱（FTIR）、氢核磁共振（¹H NMR）、场发射扫描电子显微镜-能谱分析（FESEM-EDX）和热重分析（TGA）对纳米复合材料的结构进行了表征，并通过测定对某些细菌和真菌的最低抑菌浓度（MIC）值来评估智能载体的抗菌活性。然后，通过检测纳米复合材料在生理环境pH值（pH 7.4）和肿瘤组织pH值（轻度酸性）下的释放曲线，证明了两者的pH响应方式。最后，通过MTT法和细胞周期研究评估了这些纳米复合系统对MCF7细胞系的潜在抗肿瘤活性。结果表明，新开发的纳米复合材料不仅按照预测的曲线同时释放两种抗癌药物，达到了我们的预期，而且在体外实验中表现出抗菌和抗癌特性。此外，还证明了这些载体在癌症治疗的多功能药物递送方面具有巨大潜力。
