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Synthesis, biocompatibility and gene encapsulation of poly(2-Ethyl 2-Oxazoline)-dioleoyl phosphatidylethanolamine (PEtOx-DOPE) and post-modifications with peptides and fluorescent dye coumarin
International Journal of Polymeric Materials and Polymeric Biomaterials ( IF 2.5 ) Pub Date : 2020-07-07 , DOI: 10.1080/00914037.2020.1767617
Sevgi Gulyuz 1, 2 , Duygu Bayram 1, 2 , Umut Ugur Ozkose 1, 2, 3 , Zeynep Busra Bolat 4, 5 , Polen Kocak 4 , Ongun Mehmet Saka 6 , Burcu Devrim 6 , Melek Parlak Khalily 7 , Dilek Telci 4 , Fikrettin Sahin 4 , Salih Özçubukçu 8 , Esma Sezer 2 , Mehmet Atilla Tasdelen 9 , Onur Alpturk 2 , Asuman Bozkır 6 , Ozgur Yilmaz 1
Affiliation  

Abstract

Liposome surface modifications serve great potential applications of liposomes, for instance, increasing stability, bioactive liposome conjugates, and targeted drug, gene, and image agent delivery. In this study, novel targeted lipopolymers, peptide 18/peptide 563-poly(2-ethyl-2-oxazoline)-dioleoylphosphatidyl-ethanolamine (P18/P563-PEtOx-DOPE), have been demonstrated to be successfully synthesized. The structures of P18/P563-PEtOx-DOPE were confirmed by FT-IR spectroscopy, GPC, and 1H-NMR. In this strategy, poly(2-ethyl 2-oxazoline)-modified liposomes were firstly constructed with molecular weights of 3,500 and 5,800 Da. Then, we chose PEtOx5800-DOPE because it has been obtained better particle size (88.74 ± 0.6816) according to the DLS results. Then, peptides- and dye-PEtOx lipid-based nanovesicle (LN) were prepared by peptide-18, peptide-563, and 7-mercapto-4-methyl coumarin. Genetic material (pDNA) was encapsulated into the liposomes and evaluated the encapsulation of plasmid DNA with migration by using agarose gel electrophoresis. In vitro cytotoxicity experiment results on prostate cancer and breast cancer cell lines, parallelly with the healthy prostate (PNT1A) and breast (MCF10A) epithelial cell lines, cells showed insignificant toxic effects. Thus, we can suggest a novel PEtOx phospholipid thanks to this article and its integration with ligands, which great potential for gene transfer system.



中文翻译:

聚(2-乙基 2-恶唑啉)-二油酰磷脂酰乙醇胺 (PEtOx-DOPE) 的合成、生物相容性和基因封装以及肽和荧光染料香豆素的后修饰

摘要

脂质体表面修饰服务于脂质体的巨大潜在应用,例如,增加稳定性、生物活性脂质体缀合物以及靶向药物、基因和成像剂递送。在这项研究中,新型靶向脂质聚合物肽 18/肽 563-聚(2-乙基-2-恶唑啉)-二油酰磷脂酰乙醇胺(P18/P563-PEtOx-DOPE)已被证明已成功合成。P18/P563-PEtOx-DOPE 的结构通过 FT-IR 光谱、GPC 和1 H-NMR证实。在该策略中,首先构建了分子量分别为 3,500 和 5,800 Da 的聚(2-乙基 2-恶唑啉)修饰脂质体。然后,我们选择了 PEtOx 5800-DOPE 因为根据 DLS 结果,它获得了更好的粒径 (88.74 ± 0.6816)。然后,通过肽 18、肽 563 和 7-巯基-4-甲基香豆素制备肽和染料-PEtOx 脂质纳米囊泡 (LN)。将遗传物质 (pDNA) 封装到脂质体中,并通过使用琼脂糖凝胶电泳评估质粒 DNA 的封装与迁移。对前列腺癌和乳腺癌细胞系的体外细胞毒性实验结果,平行于健康前列腺(PNT1A)和乳腺(MCF10A)上皮细胞系,细胞表现出不明显的毒性作用。因此,由于本文及其与配体的整合,我们可以提出一种新型的 PEtOx 磷脂,这在基因转移系统中具有巨大的潜力。

更新日期:2020-07-07
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