甲氨蝶呤 (MTX) 是一种常用的化疗药物，其水溶性有限，即使局部注射也能快速清除。在本研究中，我们开发了叶酸缀合 BSA 稳定的硒-ZIF-8 核/壳纳米粒子，用于靶向递送 MTX 来对抗乳腺癌。 FT-IR、XRD、SEM、TEM 和元素图分析证实了 FA-BSA@MTX@Se@ZIF-8 的成功形成。开发的纳米 DDS 的平均直径、多分散指数和 zeta 电位分别为 254.8 nm、0.17 和 - 16.5 mV。 MTX 从纳米载体中的释放行为与 pH 值相关，其中 pH 5.4 时的累积释放百分比高于 pH 7.4 时的累积释放百分比。 BSA显着改善了纳米粒子的血液相容性，用BSA修饰纳米粒子表面后，溶血百分比从12.67%下降到5.12%。 BSA@Se@ZIF-8 纳米颗粒中甲氨蝶呤的负载量使其对 4T1 细胞的 IC50 从 40.29 µg/mL 降低至 16.54 µg/mL，通过在表面缀合叶酸，该值甚至降低至 12.27 µg/mL。对荷瘤小鼠的抑制作用的体内评估表明，与游离MTX相比，FA-BSA@MTX@Se@ZIF-8导致肿瘤体积减少2.8倍，这归因于硒纳米粒子的抗癌作用、ZIF-8 的 pH 敏感性以及表面上作为靶向剂的叶酸的存在。更重要的是，组织学研究和动物体重监测证实，所开发的纳米DDS不具有明显的器官毒性。总而言之，将化疗药物纳入叶酸缀合的 BSA 稳定的硒-ZIF-8 纳米颗粒中可能会对未来的肿瘤管理领域产生重大影响。© 2024。控释协会。

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.© 2024. Controlled Release Society.