雌激素依赖性乳腺癌的有效治疗方法是化疗，使用诸如来曲唑等细胞毒性药物。然而，包括来曲唑在内的大多数抗癌药物被归类为IV类生物制品，这与低溶解度、生物利用度低和毒性显著相关。因此，开发针对性的送药系统对于克服这些挑战和限制至关重要。在这里，通过溶剂乳化蒸发法使用十二醇-聚乳酸-聚乙二醇（DPLA-co-PEG）制备的纳米胶束合成了可生物降解的LTZ负载的纳米载体。此外，癌细胞靶向叶酸（FA）被连接到纳米胶束中，以实现更有效、更安全的癌症治疗。在我们的调查中，DPLA-co-PEG和DPLA-co-PEG-FA显示出均匀和球形的形态。DPLA-co-PEG和DPLA-co-PEG-FA纳米胶束的平均直径分别为86.5和241.3 nm。我们的初步数据表明，所有测试浓度下DPLA-co-PEG和DPLA-co-PEG-FA两种纳米制剂均具有细胞相容性，细胞存活率≥90%。此外，纳米胶束的亲疏性使药物能够高效地负载和分散在水中，从而导致LTZ持续释放长达50小时。根据Higuchi模型，功能化FA的纳米胶束具有将LTZ控制释放到靶细胞的更大潜力。这个模型在实验上得到确认，LTZ含量为DPLA-co-PEG-FA的对激素依赖性人类乳腺癌细胞系MCF-7的细胞毒性明显更大（高达90%细胞死亡），与自由的LTZ和LTZ含量的DPLA-co-PEG相比。此外，当MCF-7细胞暴露在LTZ含量为DPLA-co-PEG-FA的情况下，半致死浓度（IC50）为87±1 nM，而自由LTZ和LTZ含量DPLA-co-PEG则需要更高的剂量，分别为125±2 nM和100±2 nM。总之，DPLA-co-PEG-FA代表了一种有前途的纳米药物输送系统，可控制地靶向输送化疗等药物。

An effective treatment for hormone-dependent breast cancer is chemotherapy using cytotoxic agents such as letrozole (LTZ). However, most anticancer drugs, including LTZ, are classified as class IV biopharmaceuticals, which are associated with low water solubility, poor bioavailability, and significant toxicity. As a result, developing a targeted delivery system for LTZ is critical for overcoming these challenges and limitations. Here, biodegradable LTZ-loaded nanocarriers were synthesized by solvent emulsification evaporation using nanomicelles prepared with dodecanol-polylactic acid-co-polyethylene glycol (DPLA-co-PEG). Furthermore, cancer cell-targeting folic acid (FA) was conjugated into the nanomicelles to achieve a more effective and safer cancer treatment. During our investigation, DPLA-co-PEG and DPLA-co-PEG-FA displayed a uniform and spherical morphology. The average diameters of DPLA-co-PEG and DPLA-co-PEG-FA nanomicelles were 86.5 and 241.3 nm, respectively. Our preliminary data suggest that both nanoformulations were cytocompatible, with ≥90% cell viability across all concentrations tested. In addition, the amphiphilic nature of the nanomicelles led to high drug loading and dispersion in water, resulting in the extended release of LTZ for up to 50 h. According to the Higuchi model, nanomicelles functionalized with FA have a greater potential for the controlled delivery of LTZ into target cells. This model was confirmed experimentally, as LTZ-containing DPLA-co-PEG-FA was significantly and specifically more cytotoxic (up to 90% cell death) toward MCF-7 cells, a hormone-dependent human breast cancer cell line, when compared to free LTZ and LTZ-containing DPLA-co-PEG. Furthermore, a half-maximal inhibitory concentration (IC50) of 87 ± 1 nM was achieved when MCF-7 cells were exposed to LTZ-containing DPLA-co-PEG-FA, whereas higher doses of 125 ± 2 and 100 ± 2 nM were required for free LTZ and LTZ-containing DPLA-co-PEG, respectively. Collectively, DPLA-co-PEG-FA represents a promising nanosized drug delivery system to target controllably the delivery of drugs such as chemotherapeutics.