Abstract：
Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.
摘要：
他莫昔芬（TAM）是一种经典的抗雌激素药物，通过竞争性结合雌激素受体α（ERα）来拮抗雌激素。然而,对TAM的耐药性仍然是乳腺癌治疗中的重大挑战。在这项研究中,我们旨在设计一种主动靶向给药系统来增强TAM对ER阳性乳腺癌细胞的增殖抑制作用。在这里，用染料木素(GEN)修饰壳聚糖(CS),获得主动靶向的GEN-CS。使用离子交联方法构建了负载TAM的纳米颗粒（TAM-GEN-CS-NP），以GEN-CS为载体材料,三磷酸钠(TPP)为交联剂。因此,TAM-GEN-CS-NP表现出平均尺寸为299.8nm的球形形态。包封率和载药量分别为85.77%和14.13µg/mg,分别。与免费TAM相比，TAM-GEN-CS-NP表现出明显的缓释性能。体外细胞实验表明，TAM-GEN-CS-NP对MCF-7细胞具有积极的靶向和增殖抑制作用。TAM和TAM-GEN-CS-NP的IC50分别为10.25µg/mL和7.22µg/mL，分别。更重要的是,TAM和GEN的组合指数(CI)值小于1,表明具有协同作用。因此,TAM-GEN-CS-NP具有通过主动靶向和协同治疗策略增强TAM治疗乳腺癌的潜力。
