Abstract：
In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-C3N4) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix\'s entrapment and loading efficiency are greatly improved by adding g-C3N4 nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of -42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-C3N4@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-C3N4@5-FU as a productive and targeted therapeutic approach for cancer cells.
摘要：
在这次调查中,我们提出了一种创新的pH响应型纳米复合材料,旨在解决与在癌症治疗中使用5-氟尿嘧啶(5-FU)相关的挑战.含有玉米醇溶蛋白（Z）的纳米复合材料，淀粉（S），和石墨氮化碳(g-C3N4)大分子通过水包油包水(W/O/W)双乳液技术合成，作为5-FU的载体。通过添加g-C3N4纳米片，S/Z水凝胶基质的包封和加载效率大大提高，达到45.25%和86.5%的值得注意的值，分别,药物装载效率和包封效率。通过FTIR和XRD表征验证了5-FU的成功负载，阐明纳米复合材料内的化学键和晶体特性。使用FESEM进行结构分析，连同DLS和zeta电位测量，纳米复合材料的平均尺寸为193.48nm，指示受控结构，zeta电位为-42.32mV，表示带负电荷的表面。对药物体外释放的研究表明，5-FU在酸性环境中比在生理环境中更有效和可持续地递送。这突出了所产生的纳米载体是pH敏感的事实。模拟释放动力学涉及找到代表潜在物理化学过程的正确数学条件。采用曲线拟合技术，确定了主要的释放机制，并确定了最佳拟合动力学模型。Baker动力学模型在pH7.4时表现最好,表明药物释放的主要原因是聚合物溶胀。相比之下,Higuchi模型对pH5.4时的药物释放最准确，阐明了扩散中涉及的扩散和溶解机制。更准确地说,pH7.4和5.4时的释放机制是异常运输（溶解控制），根据Korsmeyer-Peppas数学模型.与中性条件相比，S/Z/g-C3N4@5-FU纳米复合材料的pH依赖性溶胀和降解行为在酸性环境中表现出更高的溶胀和更快的降解。至关重要的是，MTT试验的结果证实了负载5-FU的纳米复合材料对U-87MG脑癌细胞的显着细胞毒性，同时表明对L929成纤维细胞无毒性。这些累积发现强调了工程化S/Z/g-C3N4@5-FU作为癌细胞的生产性和靶向治疗方法的潜力。
