Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
Colloids Surf B Biointerfaces. 2021 Jun;202:111712. doi: 10.1016/j.colsurfb.2021.111712. Epub 2021 Mar 19.
An integrated nanocomposite system comprising of manganese oxide (MnO) nanoparticles, functioning as a tumor diagnostic agent, in conjunction with polyacrylic acid (PAA) and ZIF-8, as pH-sensitive drug delivery agents, and methotrexate (MTX), operating as a tumor biomarker and a therapeutic agent (dual mechanism of action), is applied for both diagnostic intentions and controlled delivery of the drug. Physicochemical characteristics of the constructed system, MnO@PAA@ZIF-8/MTX, are investigated by several methods, including X-ray diffraction, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and electrochemical techniques. The in-vitro magnetic resonance imaging measurements was performed to show the efficiency of MnO@PAA@ZIF-8 nanocomposite as a contrast agent where a relaxivity (r) of 3.3 mM s is found. The loading ratio was found as 161 % which is four times larger than the value obtained for MnO@PAA system in the same conditions, indicating high capability of the system for MTX delivery. The application of the nanocomposite as a dual pH-sensitive nanocarrier for MTX is studied through in-vitro drug release experiments at pHs of 5.4, 6.8 and 7.4. Interestingly, the results show that a large amount of loaded MTX drug (53 %) is released from the system during incubation and dialysis at pH 5.4, compared with that (20 % and 15 %), respectively, released at pHs 6.8 and 7.4 at the same conditions. The affinity of MnO@PAA@ZIF-8/MTX nanocomposite for capturing of BT-474 and MCF-7 cancer cells was evaluated via impedance spectroscopy measurements. The results show that GC-MnO@PAA@ZIF-8/MTX electrode captures the BT-474 and MCF-7 cancer cells, respectively, by factors of ∼2 and 196 compared with L929 normal cells. This affinity also shows the high selectivity of the system for MCF-7 cancer cells compared with BT-474.
一种由氧化锰 (MnO) 纳米粒子组成的纳米复合系统，作为肿瘤诊断剂，与聚丙烯酸 (PAA) 和 ZIF-8 作为 pH 敏感的药物输送剂，以及甲氨蝶呤 (MTX) 结合使用，作为肿瘤生物标志物和治疗剂 (双重作用机制)，用于诊断和控制药物的输送。通过多种方法研究了构建的系统 MnO@PAA@ZIF-8/MTX 的物理化学特性，包括 X 射线衍射、傅里叶变换红外光谱、场发射扫描电子显微镜和电化学技术。进行了体外磁共振成像测量以显示 MnO@PAA@ZIF-8 纳米复合材料作为对比剂的效率，其中发现弛豫率 (r) 为 3.3 mM s。发现负载比为 161%，是在相同条件下获得的 MnO@PAA 系统的 4 倍，表明该系统对 MTX 输送的高能力。通过在 pH 值为 5.4、6.8 和 7.4 的体外药物释放实验研究了纳米复合材料作为 MTX 的双重 pH 敏感纳米载体的应用。有趣的是，结果表明，与在 pH 6.8 和 7.4 下孵育和透析时分别释放的 20%和 15%相比，在 pH 5.4 下从该系统中大量释放负载的 MTX 药物 (53%)。通过阻抗谱测量评估了 MnO@PAA@ZIF-8/MTX 纳米复合材料对 BT-474 和 MCF-7 癌细胞的亲和力。结果表明，与 L929 正常细胞相比，GC-MnO@PAA@ZIF-8/MTX 电极分别捕获 BT-474 和 MCF-7 癌细胞的因子约为 2 和 196。这种亲和力还表明该系统对 MCF-7 癌细胞的高选择性与 BT-474 相比。
