本研究探讨了携带 5-氟尿嘧啶 (5-FU) 或奥沙利铂 (OX) 和二甲双胍 (MET) 的基于 SPION 的二氧化硅纳米载体对结直肠癌细胞的抗癌作用。纳米载体配备了用于控制释放的 pH 响应金守门员、用于更长循环的聚乙二醇化以及用于靶向递送的叶酸 (FA)。通过研究细胞活力、细胞摄取、流式细胞术和体外克隆形成测定来评估效果。还在荷HT-29肿瘤的C57BL/6小鼠体内测试了该系统的功效，并评估了潜在的副作用。合成的纳米载体的流体动力学直径为5-FU 79.8nm和OX 85.2nm； zeta电位分别为-21和-22mV，72小时后保持稳定。 5-FU、OX 和 MET 的封装效率分别为 85%、80% 和 83%，负载能力分别为 44%、38% 和 41%。 5-FU 在酸性缓冲液中的药物释放率为 38.7%，OX 为 32.8%，MET 为 43.5%。 MTT 测定显示 FA 缀合导致毒性增加，而聚乙二醇化则降低溶血活性。与非靶向变体相比，靶向纳米载体表现出优异的细胞摄取和肿瘤定位。 5-FU-MET 和 OX-MET 纳米载体与放射治疗 (RT) 的组合显示出其抗肿瘤活性的最大效果，同时副作用最小，表明体内肿瘤靶向有效。 MRI 和 CT 成像进一步支持了这些发现。这项研究强调了 MET 与 RT 一起对靶向 5-FU 和 OX 纳米载体抑制癌细胞和肿瘤生长的协同影响，反映了 MET 的显着放射增敏特性。版权所有 © 2024 Elsevier B.V. 保留所有权利。

This study investigates the anticancer effects of SPION-based silica nanocarriers carrying 5-fluorouracil (5-FU) or oxaliplatin (OX), and metformin (MET) on colorectal cancer cells. Nanocarriers were equipped with pH-responsive gold gatekeepers for controlled release, PEGylation for longer circulation, and folic acid (FA) for targeted delivery. The effects were evaluated by investigating cell viability, cellular uptake, flow cytometry, and clonogenic assay in vitro. The efficacy of the system was also tested in vivo on C57BL/6 mice bearing HT-29 tumors, and potential side effects were evaluated Nanocarriers were synthesized with hydrodynamic diameters of 79.8 nm for 5-FU and 85.2 nm for OX; zeta potentials of -21 and -22 mV, respectively, and remained stable after 72 h. Encapsulation efficiencies were 85 % for 5-FU, 80 % for OX, and 83 % for MET, with loading capacities of 44 %, 38 %, and 41 %, respectively. Drug release in acidic buffer was 38.7 % for 5-FU, 32.8 % for OX, and 43.5 % for MET. MTT assay showed increased toxicity due to FA conjugation, while PEGylation reduced the hemolysis activity. Targeted nanocarriers demonstrated superior cellular uptake and tumor localization compared to non-targeted variants. The combination of 5-FU-MET and OX-MET nanocarriers with radiation therapy (RT) demonstrated the greatest effect on their antitumor activity, accompanied by minimal side effects indicating effective tumor targeting in vivo. MRI and CT imaging further supported these findings. This study underscores the synergistic impact of MET alongside RT on the inhibition of cancer cells and tumor growth for both targeted 5-FU and OX nanocarriers reflecting the significant radiosensitizing properties of MET.Copyright © 2024 Elsevier B.V. All rights reserved.