Dehghani Meysam, Zare-Zardini Hadi, Eslami Hossein, Ansari Mojtaba, Fesahat Farzaneh
Department of Biomedical Engineering, Meybod University, Meybod, Iran.
Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Sci Rep. 2025 Sep 29;15(1):33441. doi: 10.1038/s41598-025-19075-7.
Colorectal cancer (CRC) remains a major challenge to global health and chemotherapy, while effective, often suffers from non-specificity, limited efficacy and severe side effects. 5-Fluorouracil (5FU), a cornerstone of chemotherapy for colorectal cancer, has a short half-life and systemic toxicity. Targeted delivery systems are crucial to overcome these limitations. The aim of this study was to develop and evaluate albumin nanoparticles (ANPs) co-loaded with green-synthesized silver nanoparticles (AgNPs) and 5FU (Ag-5FU-ANPs) as a potential strategy to improve chemotherapeutic efficacy and reduce toxicity in the treatment of colorectal cancer. The AgNPs were synthesized from a green tea extract, characterized (UV-Vis, TEM/SEM, DLS) and showed a spherical morphology with an average size of 89.9 nm. Four nanoparticle formulations (ANP, Ag-ANP, 5FU-ANP, Ag-5FU-ANP) were prepared using a solvent displacement method. Characterization revealed successful encapsulation efficiency (EE) (%EE > 70-80% efficiency) and controlled release kinetics (according to the Higuchi model, > 90% release in 3 days). In vitro studies in normal human fibroblast cells (HFF) showed acceptable cytotoxicity for Ag-5FU-ANP compared to free agents, with minimal hemolysis. In a 21-day colon cancer model using Wistar rats with CT26-induced tumors, intravenous administration of Ag-5FU-ANP showed the most significant anticancer effect, reducing tumor size and tumor weight compared to other groups. Histopathological analysis confirmed increased apoptosis and decreased necrosis in the Ag-5FU-ANP group. However, while the combination therapies showed increased renal toxicity compared to ANP, Ag-5FU-ANP showed less severe hematological toxicity (anemia, leukocytosis) than 5FU monotherapy. The blood analysis confirmed these results. These results suggest that Ag-5FU-ANPs represent a promising dual drug delivery system for colorectal cancer, improving therapeutic outcomes through better localization of the drug and potential exploitation of the anti-cancer properties of AgNPs, while mitigating some systemic side effects associated with 5FU monotherapy through controlled release. Further optimization is required to balance efficacy and toxicity for potential clinical application.
结直肠癌（CRC）仍然是全球健康面临的重大挑战，化疗虽然有效，但往往存在非特异性、疗效有限和严重副作用等问题。5-氟尿嘧啶（5FU）是结直肠癌化疗的基石，但其半衰期短且具有全身毒性。靶向递送系统对于克服这些局限性至关重要。本研究的目的是开发和评估负载绿色合成银纳米颗粒（AgNPs）和5FU的白蛋白纳米颗粒（ANPs，即Ag-5FU-ANPs），作为提高结直肠癌化疗疗效和降低毒性的潜在策略。AgNPs由绿茶提取物合成，进行了表征（紫外-可见光谱、透射电子显微镜/扫描电子显微镜、动态光散射），呈现球形形态，平均粒径为89.9纳米。使用溶剂置换法制备了四种纳米颗粒制剂（ANP、Ag-ANP、5FU-ANP、Ag-5FU-ANP）。表征显示包封效率成功（包封率%EE>70-80%）且释放动力学可控（根据 Higuchi 模型，3天内释放>90%）。在正常人成纤维细胞（HFF）中的体外研究表明，与游离药物相比，Ag-5FU-ANP具有可接受的细胞毒性，溶血作用最小。在使用CT26诱导肿瘤的Wistar大鼠建立的21天结肠癌模型中，静脉注射Ag-5FU-ANP显示出最显著的抗癌效果，与其他组相比，肿瘤大小和肿瘤重量均减小。组织病理学分析证实Ag-5FU-ANP组细胞凋亡增加，坏死减少。然而，虽然联合疗法与ANP相比显示出肾毒性增加，但Ag-5FU-ANP的血液学毒性（贫血、白细胞增多）比5FU单药治疗轻。血液分析证实了这些结果。这些结果表明，Ag-5FU-ANPs是一种有前景的结直肠癌双药递送系统，通过更好地定位药物以及潜在利用AgNPs的抗癌特性提高治疗效果，同时通过控释减轻与5FU单药治疗相关的一些全身副作用。为实现潜在的临床应用，需要进一步优化以平衡疗效和毒性。
