Bolat Zeynep Büşra, Nezir Ayça Ece, Saka Ongun Mehmet, Zemheri Itır Ebru, Gülyüz Sevgi, Özköse Umut Uğur, Yilmaz Özgür, Bozkir Asuman, Telci Dilek, Şahin Fikrettin
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Ataşehir, İstanbul, Turkiye.
Department of Molecular Biology and Genetics, Hamidiye Institute of Health Sciences, University of Health Sciences-Türkiye, İstanbul, Turkiye.
Turk J Biol. 2024 Sep 5;48(5):299-307. doi: 10.55730/1300-0152.2706. eCollection 2024.
Breast cancer is one of the most common cancers and a significant cause of death in females worldwide. For effective breast cancer treatment, using systems with a promising delivery of anticancer agents is an important strategy. Peptide 18 (P18), a tumor-homing peptide, shows a high binding affinity toward breast cancer cells. Nanoliposomes are known to have enhanced accumulation ability in tumors with longer systemic circulation. In this study, Poly (2-ethyl-2-oxazoline) (PEtOx) polymers conjugated with DOPE are used to prepare PEtOx-DOPE nanoliposomes. , a mutant form of the Bik gene and a member of the BH3-only proapoptotic genes, mimics the constitutively phosphorylated form of the gene. To the best of our knowledge, this study presents a novel approach by investigating P18-conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of to the AU565 breast cancer model. A site-directed mutated was loaded into P18-PEtOx-DOPE nanoliposomes, and the targeted drug delivery system was assessed in in vitro and in vivo breast cancer models for efficiency, safety, and efficacy. The increased Bik mRNA expression levels in AU565 cells suggest a high effectiveness of the targeting PEtOx-DOPE nanoliposomes. Following the in vitro studies, the delivery of by P18-PEtOx-DOPE nanoliposomes was analyzed in CD-1 nude mice models. The animal study showed no significant difference in the tumor volume of the CD-1 nude mice treated with P18-PEtOx-DOPE-BikDD nanoliposomes compared to the free delivery of . Our preclinical studies suggest that P18-PEtOx-DOPE-BikDD nanoliposomes may be promising gene carriers for targeted breast cancer therapy. Thus, further studies should be carried out to determine the prolonged use of this drug delivery system in breast cancer therapy.
乳腺癌是全球女性中最常见的癌症之一，也是导致女性死亡的重要原因。为了有效治疗乳腺癌，使用能够有效递送抗癌药物的系统是一项重要策略。肽18（P18）是一种肿瘤归巢肽，对乳腺癌细胞具有高结合亲和力。已知纳米脂质体在肿瘤中具有增强的积累能力且全身循环时间更长。在本研究中，与二油酰磷脂酰乙醇胺（DOPE）共轭的聚（2-乙基-2-恶唑啉）（PEtOx）聚合物用于制备PEtOx-DOPE纳米脂质体。Bik基因的一种突变形式，属于仅含BH3结构域的促凋亡基因家族成员，模拟该基因的组成型磷酸化形式。据我们所知，本研究通过研究P18共轭的PEtOx-DOPE纳米脂质体（P18-PEtOx-DOPE）用于将[此处原文缺失具体物质]靶向递送至AU565乳腺癌模型，提出了一种新方法。将一个定点突变的[此处原文缺失具体物质]载入P18-PEtOx-DOPE纳米脂质体，并在体外和体内乳腺癌模型中评估该靶向药物递送系统的效率、安全性和有效性。AU565细胞中Bik mRNA表达水平的升高表明靶向PEtOx-DOPE纳米脂质体具有高效性。体外研究之后，在CD-1裸鼠模型中分析了P18-PEtOx-DOPE纳米脂质体对[此处原文缺失具体物质]的递送情况。动物研究表明，与游离递送[此处原文缺失具体物质]相比，用P18-PEtOx-DOPE-BikDD纳米脂质体处理的CD-1裸鼠的肿瘤体积没有显著差异。我们的临床前研究表明，P18-PEtOx-DOPE-BikDD纳米脂质体可能是用于靶向乳腺癌治疗的有前景的基因载体。因此，应进一步开展研究以确定该药物递送系统在乳腺癌治疗中的长期应用情况。
