Yosefi Sedighe, Sirati-Sabet Majid, Pakdel Abbas, Nabizadeh Zahra, Kokhaei Parviz, Madanchi Hamid
Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun;398(6):7301-7316. doi: 10.1007/s00210-024-03750-z. Epub 2024 Dec 30.
Triple-negative breast cancer (TNBC) is a very aggressive and deadly form of breast cancer for which chemotherapy is the only systemic treatment option. Therefore, novel and more effective targeted or combined therapies, such as specific drug delivery systems that selectively target cancer cells, have received much attention. This research aimed to investigate the effect of targeted delivery of chrysin (CH) and 5-fluorouracil (5FU) using polymer nanoparticles on MDA-MB-231 cells. In this regard, CH and 5FU were individually used as the template to polymerize L-DOPA on the surface of silica nanoparticles. Then, a CD138-targeting peptide was designed for the first time and immobilized on the surface of the polymeric nanocomposite to target TNBC. The results showed that poly(L-DOPA)-CH-peptide and poly(L-DOPA)-5FU-peptide are selective for MDA-MB-231 cells and deliver drugs to them in a targeted manner. In this study, peptide-containing nanocomposites targeting CD138 were more successful in reducing cell proliferation than peptide-free nanocomposites. Also, they increased apoptosis and cell cycle arrest in MDA-MB-231 cancer cells in vitro. The effective and targeted delivery of CH and 5FU to MDA-MB-231 cancer cells by the designed interference peptide in this study can promise an effective treatment method for inhibiting the growth and progression of cancer. However, animal studies are needed to understand the efficacy of the interfering peptide and the final designed construct.
三阴性乳腺癌(TNBC)是一种极具侵袭性和致命性的乳腺癌,化疗是其唯一的全身治疗选择。因此,新型且更有效的靶向或联合疗法,如选择性靶向癌细胞的特定药物递送系统,受到了广泛关注。本研究旨在探讨使用聚合物纳米颗粒靶向递送白杨素(CH)和5-氟尿嘧啶(5FU)对MDA-MB-231细胞的影响。在这方面,分别以CH和5FU为模板,在二氧化硅纳米颗粒表面聚合L-多巴。然后,首次设计了一种靶向CD138的肽,并将其固定在聚合物纳米复合材料表面以靶向TNBC。结果表明,聚(L-多巴)-CH-肽和聚(L-多巴)-5FU-肽对MDA-MB-231细胞具有选择性,并以靶向方式将药物递送至这些细胞。在本研究中,靶向CD138的含肽纳米复合材料在减少细胞增殖方面比不含肽的纳米复合材料更成功。此外,它们还能在体外增加MDA-MB-231癌细胞的凋亡和细胞周期停滞。本研究中通过设计的干扰肽将CH和5FU有效且靶向地递送至MDA-MB-231癌细胞,有望为抑制癌症的生长和进展提供一种有效的治疗方法。然而,需要进行动物研究以了解干扰肽和最终设计构建体的疗效。