Al-Shalabi Rolla, Lim Vuanghao, Al-Deeb Ibrahim, Kilus Melissa, Abdul Samad Nozlena
Department of Toxicology, Advanced Medical and Dental Institute, Sains@BERTAM, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia.
Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Al-Salt 19628, Jordan.
Explor Target Antitumor Ther. 2025 Jul 27;6:1002332. doi: 10.37349/etat.2025.1002332. eCollection 2025.
Angiogenesis, invasion, and tube formation are critical processes in tumor progression and metastasis. The use of nanoparticles derived from natural products presents a promising approach for targeted cancer therapy. This study evaluates the anti-angiogenic and anti-invasive effects of silver nanoparticles (MO-AgNPs) as a therapeutic strategy against these processes.
The anti-angiogenic and anti-invasive activities of MO-AgNPs were investigated using a series of in vitro and ex vivo models. These included the rat aortic ring assay, endothelial tube formation assay, cell invasion assay using endothelial cell lines (Ea.hy926), and a three-dimensional (3D) co-culture spheroid model to simulate tumor microenvironment behavior. Comparisons were made with known inhibitors: quercetin (15.11 μg/mL) and suramin (100 μg/mL).
MO-AgNPs at 12 μg/mL significantly inhibited Ea.hy926 cell invasion by 62.10% and significantly suppressed endothelial tube formation, comparable to the effect of quercetin. In the ex vivo aortic ring assay, MO-AgNPs reduced microvessel sprouting by 83.824 ± 0.081%, surpassing the inhibition achieved by suramin. Additionally, in the 3D spheroid model, MO-AgNPs at concentrations of 12 μg/mL and 6 μg/mL, as well as quercetin, significantly reduced spheroid diameter by day 14, indicating suppressed invasive potential and angiogenic support.
MO-AgNPs exhibit strong anti-angiogenic and anti-invasive effects across various tumor-relevant models, highlighting their potential as a therapeutic agent against tumor progression and angiogenesis-related diseases. These results support further investigation of MO-AgNPs as a novel nanotherapeutic for cancer treatment.
血管生成、侵袭和血管形成是肿瘤进展和转移的关键过程。使用源自天然产物的纳米颗粒为靶向癌症治疗提供了一种有前景的方法。本研究评估了银纳米颗粒（MO-AgNPs）作为针对这些过程的治疗策略的抗血管生成和抗侵袭作用。
使用一系列体外和离体模型研究了MO-AgNPs的抗血管生成和抗侵袭活性。这些模型包括大鼠主动脉环试验、内皮管形成试验、使用内皮细胞系（Ea.hy926）的细胞侵袭试验以及模拟肿瘤微环境行为的三维（3D）共培养球体模型。与已知抑制剂槲皮素（15.11μg/mL）和苏拉明（100μg/mL）进行了比较。
12μg/mL的MO-AgNPs显著抑制Ea.hy926细胞侵袭达62.10%，并显著抑制内皮管形成，其效果与槲皮素相当。在离体主动脉环试验中，MO-AgNPs使微血管芽生减少了83.824±0.081%，超过了苏拉明的抑制效果。此外，在3D球体模型中，12μg/mL和6μg/mL浓度的MO-AgNPs以及槲皮素在第14天时显著减小了球体直径，表明侵袭潜能和血管生成支持受到抑制。
MO-AgNPs在各种与肿瘤相关的模型中均表现出强大的抗血管生成和抗侵袭作用，突出了其作为针对肿瘤进展和血管生成相关疾病的治疗剂的潜力。这些结果支持进一步研究将MO-AgNPs作为一种新型癌症治疗纳米药物。
