Suppr超能文献

带有含有石胆酸和叶酸部分的聚合物外壳的磁性颗粒:对抗结肠癌的纳米勇士。

Magnetic particles with polymeric shells bearing lithocholic and folic acid moieties: Nano-warriors to fight colon cancer.

作者信息

Szymczuk Dawid, Markiewicz Karolina H, Niemirowicz-Laskowska Katarzyna, Sadowska Anna, Wołosewicz Joanna, Car Halina, Wilczewska Agnieszka Z

机构信息

Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland; Doctoral School of Exact and Natural Sciences, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland.

Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland.

出版信息

Int J Pharm. 2024 Sep 5;662:124503. doi: 10.1016/j.ijpharm.2024.124503. Epub 2024 Jul 21.

Abstract

In the study, we aimed to investigate the activity of nanoformulations containing 5-fluorouracil and polymer-magnetic hybrids bearing membrane-penetrating and ligand-receptor-recognizing agents against colorectal cancer cells. The formation and characterization of iron oxide particles covered with polymeric shells comprising lithocholic acid and folic acid moieties are presented. The efficiency of nanoformulations combined by the simple mixing of low doses of 5-fluorouracil with the obtained hybrids was demonstrated against DLD-1 and HT-29 colon cancer cells. The most pronounced cytotoxic potential against HT-29 cells was observed in the cases of particles based on block and randomly arranged copolymers functionalized by FA motifs with depletion of viable cells by approximately 50 % compared to control cells and cells treated by 5-FU applied in free form. In the case of the DLD-1 cell line, the percentage of viable DLD-1 cells decreased by about 30 to 40% after treatment with the block and randomly arranged copolymer decorated by FA-moiety, when compared to 5-FU at the free form and the untreated control. The induction of apoptosis associated with PS-translocation was determined to be the main mechanism of their cytotoxic effects. Moreover, the safety profiles of the nanoformulations were established through hemolysis assay and the analysis of the viability of human colorectal fibroblasts. It was indicated that all tested nanoparticles met the compatibility requirements at the in vitro level. It should be emphasized that in many cases, there was a significant improvement in the compatibility of hybrids with the FA motif compared to non-functionalized hybrids with the addition of 5-FU. These findings suggest that the presence of FA might modulate the toxicity of chemotherapeutic agents.

摘要

在本研究中,我们旨在研究含有5-氟尿嘧啶的纳米制剂以及带有膜穿透剂和配体-受体识别剂的聚合物-磁性杂化物对结肠癌细胞的活性。本文介绍了包覆有包含石胆酸和叶酸部分的聚合物壳的氧化铁颗粒的形成和表征。通过将低剂量的5-氟尿嘧啶与所得杂化物简单混合而组合的纳米制剂对DLD-1和HT-29结肠癌细胞的有效性得到了证明。在基于由FA基序功能化的嵌段和无规排列共聚物的颗粒的情况下,观察到对HT-29细胞最明显的细胞毒性潜力,与对照细胞和以游离形式施用的5-氟尿嘧啶处理的细胞相比,活细胞减少了约50%。在DLD-1细胞系的情况下,与游离形式的5-氟尿嘧啶和未处理的对照相比,用FA部分修饰的嵌段和无规排列共聚物处理后,存活的DLD-1细胞百分比降低了约30%至40%。与PS易位相关的细胞凋亡诱导被确定为其细胞毒性作用的主要机制。此外,通过溶血试验和人结肠成纤维细胞活力分析确定了纳米制剂的安全性。结果表明,所有测试的纳米颗粒在体外水平上均符合兼容性要求。应该强调的是,在许多情况下,与添加5-氟尿嘧啶的未功能化杂化物相比,具有FA基序的杂化物的兼容性有了显著提高。这些发现表明,FA的存在可能会调节化疗药物的毒性。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验