Methotrexate (MTX), an anti-neoplastic agent used for breast cancer treatment, has restricted clinical applications due to poor water solubility, non-specific targeting and adverse side effects. To overcome these limitations, MTX was co-encapsulated with an active-targeting platform known as superparamagnetic iron oxide nanoparticles (SPIONs) in a lipid-based homing system, nanostructured lipid carrier (NLC). This multi-modal therapeutic regime was successfully formulated with good colloidal stability, bio- and hemo-compatibility. MTX-SPIONs co-loaded NLC was time-dependent cytotoxic towards MDA-MB-231 breast cancer cell line with IC₅₀ values of 137 μg/mL and 12 μg/mL at 48 and 72 h, respectively. The MTX-SPIONs co-loaded NLC was internalized in the MDA-MB-231 cells via caveolae-mediated endocytosis in a time-dependent manner, and the superparamagnetic properties were sufficient to induce, under a magnetic field, a localized temperature increase at cellular level resulting in apoptotic cell death. In conclusion, MTX-SPIONs co-loaded NLC is a potential magnetic guiding multi-modal therapeutic system for the treatment of breast cancer.

甲氨蝶呤（MTX）是一种用于乳腺癌治疗的抗肿瘤药，由于水溶性差，非特异性靶向作用和不良副作用而受到限制的临床应用。为了克服这些限制，MTX与称为超顺磁性氧化铁纳米粒子（SPIONs）的主动靶向平台共封装在基于脂质的归巢系统，纳米结构脂质载体（NLC）中。该多模式治疗方案已成功制定，具有良好的胶体稳定性，生物和血液相容性。MTX-SPIONs与IC ₅₀共同加载NLC对MDA-MB-231乳腺癌细胞系具有时间依赖性细胞毒性分别在48和72 h时的137μg/ mL和12μg/ mL值。通过空洞介导的内吞作用，MTD-SPIONs的NLC共装载于MDA-MB-231细胞中，并呈时间依赖性，并且超顺磁特性足以在磁场下诱导细胞局部温度升高。水平导致凋亡细胞死亡。总之，MTX-SPIONs共装NLC是用于治疗乳腺癌的潜在磁导多峰治疗系统。