Shahbazi Soraya, Tafvizi Farzaneh, Naseh Vahid
Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.
Heliyon. 2024 Apr 30;10(9):e30503. doi: 10.1016/j.heliyon.2024.e30503. eCollection 2024 May 15.
Considering its overall impact on human health, letrozole (Let) has been described as having significant efficacy that could be improved by developing drug delivery systems. Considering the side effects of Let, this study aims to encapsulate Let in liposomes and PEGylated liposome nanoparticles (Lipo-Let-PEG) and evaluate the cytotoxic effects on the MCF-7 breast cancer cell line. For this purpose, the Lipo-Let-PEG formulation was designed and characterized by SEM, DLS, and FTIR methods, and the drug release from the optimized formulation and the stability of the optimized Lipo-Let-PEG were measured. Furthermore, the cytotoxicity and apoptotic studies were performed using MTT assay and flow cytometric analysis. According to the experimental data, the vesicle size and EE% were 170.05 ± 4.15 nm and 87.21 ± 1.36 %, respectively. The cumulative release from Lipo-Let-PEG at pH 5.4 and 7.4 was also approximately 60 % and 50 %, respectively. MTT results showed that Lip-Let-PEG produced more drug cytotoxicity than Lip-Let against MCF-7 cancer cells and was more compatible with normal cells. The results of apoptosis and cell cycle arrest using flow cytometry show that Lipo-Let-PEG caused the most significant increase in apoptotic rates and cell cycle arrest in cancer cells compared to other treated groups. In conclusion, Lipo-Let-PEG can be used as an anticancer agent by arresting cell cycle progression and inducing apoptosis, which can be applied in future studies to prevent breast cancer development.
考虑到来曲唑（Let）对人类健康的总体影响，其已被描述为具有显著疗效，通过开发药物递送系统可进一步提高疗效。鉴于Let的副作用，本研究旨在将来曲唑包封于脂质体和聚乙二醇化脂质体纳米粒（Lipo-Let-PEG）中，并评估其对MCF-7乳腺癌细胞系的细胞毒性作用。为此，设计了Lipo-Let-PEG制剂，并通过扫描电子显微镜（SEM）、动态光散射（DLS）和傅里叶变换红外光谱（FTIR）方法对其进行表征，同时测定了优化制剂的药物释放情况以及优化后的Lipo-Let-PEG的稳定性。此外，使用MTT法和流式细胞术分析进行了细胞毒性和凋亡研究。根据实验数据，囊泡大小和包封率分别为170.05±4.15nm和87.21±1.36%。Lipo-Let-PEG在pH 5.4和7.4条件下的累积释放率分别约为60%和50%。MTT结果表明，与Lipo-Let相比，Lip-Let-PEG对MCF-7癌细胞产生了更强的药物细胞毒性，且与正常细胞的相容性更好。流式细胞术检测凋亡和细胞周期阻滞的结果表明，与其他处理组相比，Lipo-Let-PEG导致癌细胞凋亡率和细胞周期阻滞的增加最为显著。总之，Lipo-Let-PEG可通过阻滞细胞周期进程和诱导凋亡用作抗癌剂，可应用于未来预防乳腺癌发展的研究中。
