PEtOx-DOPE nanoliposomes functionalized with peptide 563 in targeted BikDDA delivery to prostate cancer.

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2024-05-23 eCollection Date: 2024-01-01 DOI:10.55730/1300-0152.2693
Ayca Ece Nezir, Zeynep Büşra Bolat, Ongun Mehmet Saka, Itır Ebru Zemheri, Sevgi Gülyüz, Umut Uğur Özköse, Özgür Yilmaz, Asuman Bozkir, Fikrettin Şahin, Dilek Telci
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Abstract

Background: Nanocarrier-based systems have cultivated significant improvements in prostate cancer therapy. However, the efforts are still limited in clinical applicability, and more research is required for the development of effective strategies. Here, we describe a novel nanoliposomal system for targeted apoptotic gene delivery to prostate cancer.

Methods: Poly (2-ethyl-2-oxazoline) (PEtOx) dioleoyl phosphatidylethanolamine (DOPE) nanoliposomes were conjugated with the prostate-specific membrane antigen (PSMA)-targeting peptide GRFLTGGTGRLLRIS (P563) and loaded with BikDDA, a mutant form of the proapoptotic Bik. We selected 22Rv1 cells with moderate upregulation of PSMA to test the in vitro uptake, cell death, and in vivo anticancer activity of our formulation, P563-PEtOx-DOPE-BikDDA.

Results: BikDDA was upregulated in 22Rv1 cells, inducing cell death, and CD-1 nude mice xenografts administered with the formulation showed significant tumor regression.

Conclusion: We suggest that P563-PEtOx-DOPE-BikDDA nanoliposomes can serve as prominent gene carriers against prostate cancer.

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用多肽 563 功能化的 PEtOx-DOPE 纳米脂质体在前列腺癌中靶向输送 BikDDA。
背景:基于纳米载体的系统在前列腺癌治疗方面取得了重大进展。然而,这些努力在临床应用方面仍然有限,需要更多的研究来开发有效的策略。在此,我们介绍一种新型纳米脂质体系统,用于前列腺癌凋亡基因的靶向递送:方法:聚(2-乙基-2-噁唑啉)(PEtOx)二油酰磷脂酰乙醇胺(DOPE)纳米脂质体与前列腺特异性膜抗原(PSMA)靶向肽 GRFLTGGTGRLLRIS(P563)共轭,并载入促凋亡 Bik 的突变形式 BikDDA。我们选择了 PSMA 中度上调的 22Rv1 细胞,以测试我们的制剂 P563-PEtOx-DOPE-BikDDA 的体外吸收、细胞死亡和体内抗癌活性:结果:BikDDA 在 22Rv1 细胞中上调,诱导细胞死亡,使用该制剂的 CD-1 裸鼠异种移植显示肿瘤显著消退:结论:我们认为P563-PEtOx-DOPE-BikDDA纳米脂质体可作为抗前列腺癌的重要基因载体。
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