Ahmadi-Kashani Mina, Dehghani Hossein, Zarrabi Ali
Department of Inorganic Chemistry, Faculty of Chemistry, University of Kashan, P.O. Box 87317-51167, Kashan, Iran.
Department of Inorganic Chemistry, Faculty of Chemistry, University of Kashan, P.O. Box 87317-51167, Kashan, Iran.
Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:111055. doi: 10.1016/j.msec.2020.111055. Epub 2020 May 6.
In this work, for the first time, a novel pH-sensitive biocompatible multifunctional nanocarrier was fabricated by the combination of MgAl-layered double hydroxide, MnO nanoparticles, N-graphene quantum dot and polyaniline (PANI/N-GQD/MO/LDH) for doxorubicin (DOX) delivery in breast cancer cells. Electrochemical techniques, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), were employed for proving the surface modification process. The integration of polyaniline on the surface of the nanocarrier provides ultrahigh DOX encapsulation up to 90% and possesses a slow-release behavior (4% after 72 h) under normal physiological conditions. However, releasing ~80% of the drug in a low-pH environment as a model of the extracellular tumor environment happened, presenting a pH-triggered release. The cell viability using MTT assay reveals that the DOX/PANI/N-GQD/MO/LDH had no apparent adverse effect on the viability of human L929 normal cells. Furthermore, a significant inhibition ratio against human breast cancer cell lines (MCF-7) was observed when the cells were treated with the DOX-loaded PANI/N-GQD/MO/LDH nanocarrier, suggesting that this nanocarrier could increase the therapeutic efficacy of DOX. The hemolysis rates (HRs) of human fresh blood, coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) revealed the excellent blood compatibility of the nanocarrier. Thus, the nano-vehicle designed in this study could be used as a novel multifunctional and synergistic, pH-triggered platform for delivering various anti-cancer drugs and other biomedical applications.
在本研究中，首次通过将镁铝层状双氢氧化物、二氧化锰纳米颗粒、氮掺杂石墨烯量子点和聚苯胺（PANI/N-GQD/MO/LDH）相结合，制备了一种新型的pH敏感生物相容性多功能纳米载体，用于在乳腺癌细胞中递送阿霉素（DOX）。采用包括循环伏安法（CV）和差分脉冲伏安法（DPV）在内的电化学技术来证明表面改性过程。聚苯胺在纳米载体表面的整合提供了高达90%的超高阿霉素包封率，并且在正常生理条件下具有缓释行为（72小时后释放4%）。然而，在作为细胞外肿瘤环境模型的低pH环境中，约80%的药物发生释放，呈现出pH触发释放。使用MTT法检测细胞活力表明，DOX/PANI/N-GQD/MO/LDH对人L929正常细胞的活力没有明显的不良影响。此外，当用人乳腺癌细胞系（MCF-7）处理负载DOX的PANI/N-GQD/MO/LDH纳米载体时，观察到显著的抑制率，这表明该纳米载体可以提高阿霉素的治疗效果。人新鲜血液的溶血率（HRs）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）和补体激活（C3和C4水平）揭示了该纳米载体具有优异的血液相容性。因此，本研究设计的纳米载体可作为一种新型的多功能协同pH触发平台，用于递送各种抗癌药物及其他生物医学应用。
