Phytoestrogen-derived multifunctional ligands for targeted therapy of breast cancer

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-NH(2)) 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.