Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Sci Rep. 2023 Jul 8;13(1):11090. doi: 10.1038/s41598-023-37668-y.
Protein-based nanocarriers have demonstrated good potential for cancer drug delivery. Silk sericin nano-particle is arguably one of the best in this field. In this study, we developed a surface charge reversal sericin-based nanocarrier to co-deliver resveratrol and melatonin (MR-SNC) to MCF-7 breast cancer cells as combination therapy. MR-SNC was fabricated with various sericin concentrations via flash-nanoprecipitation as a simple and reproducible method without complicated equipment. The nanoparticles were subsequently characterized for their size, charge, morphology and shape by dynamic light scattering (DLS) and scanning electron microscope (SEM). Nanocarriers chemical and conformational analysis were done by fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) respectively. In vitro drug release was determined at different pH values (7.45, 6.5 and 6). The cellular uptake and cytotoxicity were studies using breast cancer MCF-7 cells. MR-SNC fabricated with the lowest sericin concentration (0.1%), showed a desirable 127 nm size, with a net negative charge at physiological pH. Sericin structure was preserved entirely in the form of nano-particles. Among the three pH values we applied, the maximum in vitro drug release was at pH 6, 6.5, and 7.4, respectively. This pH dependency showed the charge reversal property of our smart nanocarrier via changing the surface charge from negative to positive in mildly acidic pH, destructing the electrostatic interactions between sericin surface amino acids. Cell viability studies demonstrated the significant toxicity of MR-SNC in MCF-7 cells at all pH values after 48 h, suggesting a synergistic effect of combination therapy with the two antioxidants. The efficient cellular uptake of MR-SNC, DNA fragmentation and chromatin condensation was found at pH 6. Nutshell, our result indicated proficient release of the entrapped drug combination from MR-SNC in an acidic environment leading to cell apoptosis. This work introduces a smart pH-responsive nano-platform for anti-breast cancer drug delivery.
基于蛋白质的纳米载体在癌症药物传递方面表现出了良好的应用潜力。丝胶纳米颗粒在该领域中可以说是表现最好的之一。在这项研究中，我们开发了一种表面电荷反转丝胶纳米载体，用于 MCF-7 乳腺癌细胞的共递送达瑟维醇和褪黑素（MR-SNC）作为联合治疗。MR-SNC 是通过闪蒸纳米沉淀法制备的，该方法使用不同的丝胶浓度，操作简单且可重复性高，无需复杂的设备。通过动态光散射（DLS）和扫描电子显微镜（SEM）对纳米颗粒的大小、电荷、形态和形状进行了表征。傅里叶变换红外光谱（FT-IR）和圆二色性（CD）分别用于纳米载体的化学和构象分析。在不同的 pH 值（7.45、6.5 和 6）下进行了体外药物释放实验。使用乳腺癌 MCF-7 细胞研究了细胞摄取和细胞毒性。用最低丝胶浓度（0.1%）制备的 MR-SNC 表现出理想的 127nm 大小，在生理 pH 值下带净负电荷。丝胶结构完全以纳米颗粒的形式保留。在我们应用的三个 pH 值中，在 pH 6、6.5 和 7.4 时，体外药物释放量最大。这种 pH 依赖性表明，通过在轻度酸性 pH 值下改变表面电荷，使我们的智能纳米载体的表面电荷从负变为正，从而显示出智能纳米载体的电荷反转特性，破坏丝胶表面氨基酸之间的静电相互作用。细胞活力研究表明，在所有 pH 值下，MR-SNC 在 MCF-7 细胞中的毒性在 48 小时后均显著，表明两种抗氧化剂联合治疗具有协同作用。在 pH 6 时，发现 MR-SNC 的细胞摄取效率高，DNA 片段化和染色质浓缩。总之，我们的结果表明，MR-SNC 能够在酸性环境中有效地释放包封的药物组合，从而导致细胞凋亡。这项工作介绍了一种用于抗乳腺癌药物传递的智能 pH 响应纳米平台。
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