Department of Biotechnology, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
Department of Life Science Engineering, Faculty of New Science and Technologies, University of Tehran, Tehran, Iran.
Int J Biol Macromol. 2023 Jun 15;240:124345. doi: 10.1016/j.ijbiomac.2023.124345. Epub 2023 Apr 11.
Cancer, as one of the most challenging diseases of the last century, has a significant number of patients and deaths every year. Various strategies have been explored for the treatment of cancer. Chemotherapy is one of the methods of treating cancer. Doxorubicin is one of the compounds used in chemotherapy to kill cancer cells. Due to their unique properties and low toxicity, metal oxide nanoparticles are effective in combination therapy and increase the effectiveness of anti-cancer compounds. The limited in vivo circulatory period, poor solubility, and inadequate penetration of doxorubicin (DOX) restrict its use in cancer treatment, notwithstanding its attractive characteristics. It is possible to circumvent some of the difficulties in cancer therapy by using green synthesized pH-responsive nanocomposite consisting of polyvinylpyrrolidone (PVP), titanium dioxide (TiO) modified with agarose (Ag) macromolecules. TiO incorporation into the PVP-Ag nanocomposite resulted in limited increased loading and encapsulation efficiencies from 41 % to 47 % and 84 % to 88.5 %, respectively. DOX diffusion among normal cells is prevented by the PVP-Ag-TiO nanocarrier at pH = 7.4, though the acidic intracellular microenvironments activate the PVP-Ag-TiO nanocarrier at pH = 5.4. Characterization of the nanocarrier was performed using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and zeta potential. The average particle size and the zeta potential of the particles showed values of 349.8 nm and +57 mV, respectively. In vitro release after 96 h showed a release rate of 92 % at pH 7.4 and a release rate of 96 % at pH 5.4. Meanwhile, the initial release after 24 h was 42 % for pH 7.4 and 76 % for pH 5.4. As shown by an MTT analysis on MCF-7 cells, the toxicity of DOX-loaded PVP-Ag-TiO nanocomposite was substantially greater than that of unbound DOX and PVP-Ag-TiO. After integrating TiO nanomaterials into the PVP-Ag-DOX nanocarrier, flow cytometry data showed a greater stimulation of cell death. These data indicate that the DOX-loaded nanocomposite is a suitable alternative for drug delivery systems.
癌症作为上个世纪最具挑战性的疾病之一，每年都有大量的患者和死亡人数。人们已经探索了各种策略来治疗癌症。化疗是治疗癌症的方法之一。多柔比星是化疗中用于杀死癌细胞的化合物之一。由于金属氧化物纳米粒子具有独特的性质和低毒性，它们在联合治疗中很有效，可以提高抗癌化合物的疗效。多柔比星（DOX）的体内循环半衰期有限、溶解度低、渗透不足，尽管具有吸引力的特性，但限制了其在癌症治疗中的应用。通过使用由聚乙烯吡咯烷酮（PVP）、琼脂糖（Ag）修饰的二氧化钛（TiO）组成的绿色合成 pH 响应纳米复合材料，可以规避癌症治疗中的一些困难。在 pH = 7.4 时，PVP-Ag-TiO 纳米载体可以阻止 DOX 在正常细胞中的扩散，尽管在 pH = 5.4 时，酸性细胞内微环境会激活 PVP-Ag-TiO 纳米载体。使用 X 射线衍射（XRD）、傅里叶变换红外（FTIR）分光光度法、场发射扫描电子显微镜（FE-SEM）、动态光散射（DLS）和zeta 电位对纳米载体进行了表征。纳米载体的平均粒径和zeta 电位分别为 349.8nm 和 +57mV。96 小时后体外释放显示，在 pH 7.4 时释放率为 92%，在 pH 5.4 时释放率为 96%。同时，在 pH 7.4 时初始释放率为 42%，在 pH 5.4 时初始释放率为 76%。MTT 分析 MCF-7 细胞表明，负载 DOX 的 PVP-Ag-TiO 纳米复合材料的毒性明显大于游离 DOX 和 PVP-Ag-TiO。将 TiO 纳米材料整合到 PVP-Ag-DOX 纳米载体中后，流式细胞术数据显示细胞死亡的刺激更大。这些数据表明，负载 DOX 的纳米复合材料是一种合适的药物传递系统替代品。
