Department of Molecular Biology and Genetics, Faculty of Science, Izmir Institute of Technology, Urla/Izmir 35430, Turkey.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:175-185. doi: 10.1016/j.colsurfb.2017.05.012. Epub 2017 May 10.
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance. The physicochemical properties of the nanoparticles were characterized based on the combination of several techniques: dynamic light scattering (DLS), zeta-potential measurement, Fourier transform infrared spectroscopy (FTIR), electron microscopy techniques (SEM and STEM with EDX) and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated enhanced intracellular delivery and retention of nanoparticles in the cytoplasm and efficient reduction of cancer cell viability in drug-resistant lung carcinoma A549/DOX cell lines. This did not affect internalization and viability of an immortalized human lung epithelial cell line BEAS-2B. Moreover, proapoptotic and antiproliferative studies showed that Fe3O4@SiO2(FITC)-BTN/QUR/DOX nanoparticles can promote apoptosis, inhibit tumor cell proliferation, and enhance the chemotherapeutic effects of DOX against multidrug resistance. These results confirm that this multifunctional platform possesses significant synergy between QUR and DOX and is promising for development as an antitumor treatment in cancer therapy.
经典的化疗使用化学治疗剂作为抗癌治疗的主要手段。然而，多药耐药性的发展限制了当前癌症治疗的效果。将化学治疗剂与药理学方法结合的纳米生物缀合物可能会提高化学治疗剂的疗效。在此，我通过描述 pH 响应的 Fe3O4@SiO2（FITC）-BTN/QUR/DOX 多功能纳米粒子的合成和测试来解决这个问题。这些粒子旨在调节耐药性调节因子，并增强 DOX 对耐药性的疗效。通过几种技术的结合，对纳米粒子的物理化学性质进行了表征：动态光散射（DLS）、zeta 电位测量、傅里叶变换红外光谱（FTIR）、电子显微镜技术（SEM 和 STEM 与 EDX）和体外 pH 依赖性释放研究。细胞摄取和细胞毒性实验表明，纳米粒子在细胞质中的内体传递和保留增强，并且能够有效降低耐药性肺癌 A549/DOX 细胞系中癌细胞的活力。这不会影响永生的人肺上皮细胞系 BEAS-2B 的内化和活力。此外，促凋亡和抗增殖研究表明，Fe3O4@SiO2（FITC）-BTN/QUR/DOX 纳米粒子可以促进细胞凋亡、抑制肿瘤细胞增殖，并增强 DOX 对多药耐药性的化疗效果。这些结果证实，这种多功能平台在 QUR 和 DOX 之间具有显著的协同作用，有望作为癌症治疗中的抗肿瘤治疗方法得到发展。
