纳米靶向递送系统已广泛用于乳腺肿瘤药物递送。由于雌激素受体在多种肿瘤细胞中过度表达，因此被认为是重要的药物递送靶标受体。然而，靶向配体对活性递送系统的安全性和有效性具有重要影响，限制了纳米颗粒的临床转化。植物雌激素具有良好的生物安全特性，并与雌激素受体具有一定的亲和力。本研究采用分子对接方法，在多种植物雌激素中选择丹参酮IIA（Tan IIA）作为目标配体，并进行了一些修饰，用于纳米递送系统中。修饰后的Tan IIA（Tan-NH2）表现出良好的生物安全性，并展示了靶向肿瘤、抗肿瘤和抑制肿瘤转移的效果。此外，通过化学修饰，将该配体与抗肿瘤药物Dox负载的介孔硅纳米颗粒（MSN）结合形成纳米复合物Tan-Dox-MSN。Tan-Dox-MSN具有均匀的粒径、良好的分散性和高药物载荷能力。体内和体外的验证实验显示，它还具有更好的靶向能力、抗肿瘤效果和对正常器官的低毒性。这些结果支持了植物雌激素与雌激素受体具有高亲和力，可以提高纳米靶向递送系统在乳腺肿瘤中的治疗效果的观点。©2023年沈阳药科大学。由Elsevier B.V.发表。

Nano-targeted delivery systems have been widely used for breast tumor drug delivery. Estrogen receptors are considered to be significant drug delivery target receptors due to their overexpression in a variety of tumor cells. However, targeted ligands have a significant impact on the safety and effectiveness of active delivery systems, limiting the clinical transformation of nanoparticles. Phytoestrogens have shown good biosafety characteristics and some affinity with the estrogen receptor. In the present study, molecular docking was used to select tanshinone IIA (Tan IIA) among phytoestrogens as a target ligand to be used in nanodelivery systems with some modifications. Modified Tan IIA (Tan-NH2) showed a good biosafety profile and demonstrated tumor-targeting, anti-tumor and anti-tumor metastasis effects. Moreover, the ligand was utilized with the anti-tumor drug Dox-loaded mesoporous silica nanoparticles via chemical modification to generate a nanocomposite Tan-Dox-MSN. Tan-Dox-MSN had a uniform particle size, good dispersibility and high drug loading capacity. Validation experiments in vivo and in vitro showed that it also had a better targeting ability, anti-tumor effect and lower toxicity in normal organs. These results supported the idea that phytoestrogens with high affinity for the estrogen receptor could improve the therapeutic efficacy of nano-targeted delivery systems in breast tumors.© 2023 Shenyang Pharmaceutical University. Published by Elsevier B.V.