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用抗血管生成和抗肿瘤肽A7R修饰的氧化铁基纳米颗粒的物理化学性质及体外细胞毒性

Physicochemical properties and in vitro cytotoxicity of iron oxide-based nanoparticles modified with antiangiogenic and antitumor peptide A7R.

作者信息

Niescioruk Anna, Nieciecka Dorota, Puszko Anna K, Królikowska Agata, Kosson Piotr, Perret Gerard Y, Krysinski Pawel, Misicka Aleksandra

机构信息

Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.

Department of Neuropeptides, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.

出版信息

J Nanopart Res. 2017;19(5):160. doi: 10.1007/s11051-017-3859-x. Epub 2017 Apr 26.

Abstract

Superparamagnetic iron oxide-based nanoparticles (SPIONs) are promising carriers as targeted drug delivery vehicles, because they can be guided to their target with the help of an external magnetic field. Functionalization of nanoparticles' surface with molecules, which bind with high affinity to receptors on target tissue significantly facilitates delivery of coated nanoparticles to their targeted site. Here, we demonstrate conjugation of an antiangiogenic and antitumor peptide ATWLPPR (A7R) to SPIONs modified with sebacic acid (SPIONs-SA). Successful conjugation was confirmed by various analytical techniques (FTIR, SERS, SEM-EDS, TEM, TGA). Cell cytotoxicity studies, against two cell lines (HUVEC and MDA-MB-231) indicated that SPIONs modified with A7R reduced HUVEC cell viability at concentrations higher than 0.01 mg Fe/mL, in comparison to cells that were exposed to either the nanoparticles modified with sebacic acid or A7R peptide solely, what might be partially caused by a process of internalization.

摘要

超顺磁性氧化铁基纳米颗粒(SPIONs)作为靶向给药载体具有广阔前景,因为它们可以在外部磁场的帮助下被引导至目标部位。用与靶组织上的受体具有高亲和力的分子对纳米颗粒表面进行功能化,可显著促进包被纳米颗粒向其靶向部位的递送。在此,我们展示了抗血管生成和抗肿瘤肽ATWLPPR(A7R)与用癸二酸修饰的SPIONs(SPIONs-SA)的缀合。通过各种分析技术(傅里叶变换红外光谱、表面增强拉曼光谱、扫描电子显微镜-能谱分析、透射电子显微镜、热重分析)证实了成功的缀合。针对两种细胞系(人脐静脉内皮细胞和MDA-MB-231)的细胞毒性研究表明,与单独暴露于用癸二酸修饰的纳米颗粒或A7R肽的细胞相比,用A7R修饰的SPIONs在浓度高于0.01 mg Fe/mL时会降低人脐静脉内皮细胞的活力,这可能部分是由内化过程引起的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a5c/5406482/6ad51de52b7d/11051_2017_3859_Fig1_HTML.jpg

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