Hashemi Zahra, Kaveh Zenjanab Masoumeh, Pourbakhsh Mehdi, Doustmihan Abolfazl, Fathi Marziyeh, Jahanban Esfahlan Rana
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Med Oncol. 2025 Jun 12;42(7):256. doi: 10.1007/s12032-025-02796-0.
This study focuses on developing a novel nanoformulation involving hyaluronic acid (HA) coated niosomes (NIOs) containing Fingolimod (FTY720) and quantum dots (QDs) for targeted therapy and metastasis inhibition of triple-negative breast cancer (TNBC). HNio@QDFTY720 NPs were synthesized via thin film hydration method (TFH), resulting in a size of 126.4 nm, a polydispersity index (PDI) of 0.476, and a zeta potential of - 17.6 mV. The encapsulation efficiency was determined to be 98.5%, with drug release studies revealing a pH-sensitive release profile approximately 50% release at pH 7.4, compared to 87.32% at pH 5.8, within 72 h. Cellular uptake studies demonstrated that HNio@QD NPs significantly enhanced drug localization in CD44 + MDA-MB-231 cells. MTT assay indicated that Nio@FTY720 exhibited greater cytotoxicity than the free drug, with HNio@QDFTY720 showing the highest efficacy across all tested concentrations. Annexin V-FITC/PI analysis confirmed induction of massive apoptosis and necrotic cell death, and complete inhibition of cell migration by wound healing assay achieved by HNio@QDFTY720 compared to free drug and control. Bioinformatics study confirmed that majority of Fingolimod target genes were enriched in cell motility, migration and movement and were highly correlated with survival status of breast cancer patients. These findings suggest that niosomal formulation of FTY720 significantly enhances cytotoxic effects against TNBC and represent a promising strategy for improving therapeutic outcomes in metastatic TNBC through targeted drug delivery.
本研究聚焦于开发一种新型纳米制剂，该制剂包含透明质酸（HA）包被的载有芬戈莫德（FTY720）和量子点（QDs）的脂质体（NIOs），用于三阴性乳腺癌（TNBC）的靶向治疗和转移抑制。通过薄膜水化法（TFH）合成了HNio@QDFTY720纳米颗粒，其尺寸为126.4纳米，多分散指数（PDI）为0.476，zeta电位为 -17.6毫伏。测定包封率为98.5%，药物释放研究显示其具有pH敏感的释放曲线，在pH 7.4时约50%释放，而在pH 5.8时72小时内释放87.32%。细胞摄取研究表明，HNio@QD纳米颗粒显著增强了药物在CD44 + MDA-MB-231细胞中的定位。MTT试验表明，Nio@FTY720比游离药物表现出更大的细胞毒性，在所有测试浓度下，HNio@QDFTY720显示出最高的疗效。膜联蛋白V-FITC/PI分析证实诱导了大量凋亡和坏死性细胞死亡，与游离药物和对照相比，HNio@QDFTY720通过伤口愈合试验实现了对细胞迁移的完全抑制。生物信息学研究证实，大多数芬戈莫德靶基因富集于细胞运动、迁移和移动，并且与乳腺癌患者的生存状态高度相关。这些发现表明，FTY720的脂质体制剂显著增强了对TNBC的细胞毒性作用，代表了一种通过靶向药物递送改善转移性TNBC治疗效果的有前景的策略。
