Abstract This study aimed to improve the therapeutic efficacy of doxorubicin (DOX) as an anticancer drug via loading it in the nanostructure. Therefore, for the first time, a new stimuli-responsive brushes copolymer decorated on the magnetic graphene oxide surface (MG-PB) fabricated, as well as, its capability as a targeted and stimuli-responsive drug delivery nanostructure was evaluated as in vitro. In this regard, at first, the magnetic graphene oxide nanohybrid (MG) was synthesized. Modification of the MG with triethoxyvinylsilane (TEVS) introduced the vinylic groups on the MG surface (MG-TEVS) and offered the polymerization possibility of the acrylic monomers from the MG surface. The copolymer brushes of N-isopropylacrylamide (NIPAM) and acrylated β-cyclodextrin (Ac-β-CD) were grown from the MG-TEVS surface. The Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM) analysis used to explore the successful growth of the PB brushes. The lower critical solution temperature (LCST) of the prepared nanosystem was determined at about 35 °C. DOX was loaded about 50.15% in MG-PB. The drug release results displayed the controlled release profile with ∼ 65% of DOX release in pH 5.0, 40 °C. The obtained drug release kinetic results demonstrated that the first-order kinetic model is more fitted with experimental data and DOX release follows from the Fickian mechanism. Cell viability confirmed the biocompatibility of the MG-PB. Additionally, the quantitative and qualitative cellular uptake, 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell cycle tests revealed the high anticancer performance of drug-loaded nanocarrier through the penetration within the cells and their killing as a result of DOX release. The targeted and stimuli-responsive drug release capability of the MG-BB could be the valuable advantages, hence, obtained results suggest the great potential of the ternary MG-PB hybrid nanostructure as a controlled anticancer drug delivery vehicle.

中文翻译：

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用于药物递送应用的磁性氧化石墨烯混合纳米结构装饰的智能和生物相容性刷状共聚物的制造

摘要 本研究旨在通过将多柔比星 (DOX) 负载到纳米结构中来提高其作为抗癌药物的治疗效果。因此，首次在体外评估了装饰在磁性氧化石墨烯表面 (MG-PB) 上的新型刺激响应刷共聚物及其作为靶向和刺激响应药物递送纳米结构的能力。在这方面，首先合成了磁性氧化石墨烯纳米杂化物（MG）。用三乙氧基乙烯基硅烷 (TEVS) 对 MG 进行改性在 MG 表面 (MG-TEVS) 上引入了乙烯基，并提供了从 MG 表面聚合丙烯酸单体的可能性。N-异丙基丙烯酰胺 (NIPAM) 和丙烯酸酯化 β-环糊精 (Ac-β-CD) 的共聚物刷从 MG-TEVS 表面生长。傅里叶变换红外 (FT-IR)、X 射线衍射 (XRD)、扫描电子显微镜 (SEM) 和原子力显微镜 (AFM) 分析用于探索 PB 刷的成功生长。制备的纳米系统的下临界溶解温度 (LCST) 确定为约 35 °C。DOX 在 MG-PB 中的负载量约为 50.15%。药物释放结果显示控制释放曲线，在 pH 5.0、40 °C 下释放约 65% 的 DOX。获得的药物释放动力学结果表明，一级动力学模型更符合实验数据，DOX 释放遵循 Fickian 机制。细胞活力证实了 MG-PB 的生物相容性。此外，定量和定性细胞摄取，4',6-二脒基-2-苯基吲哚（DAPI）染色，细胞周期测试揭示了载药纳米载体的高抗癌性能，通过细胞内的渗透和 DOX 释放导致的杀伤。MG-BB 的靶向和刺激响应药物释放能力可能是有价值的优势，因此，获得的结果表明三元 MG-PB 混合纳米结构作为受控抗癌药物递送载体的巨大潜力。