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用于柔红霉素向结肠癌MC38细胞局部持续递送的聚电解质油核纳米载体:与聚乙二醇化外壳相关的多糖多层膜情况

Polyelectrolyte Oil-Core Nanocarriers for Localized and Sustained Delivery of Daunorubicin to Colon Carcinoma MC38 Cells: The Case of Polysaccharide Multilayer Film in Relation to PEG-ylated Shell.

作者信息

Bazylińska Urszula, Pietkiewicz Jadwiga, Rossowska Joanna, Chodaczek Grzegorz, Gamian Andrzej, Wilk Kazimiera A

机构信息

Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland.

Department of Medical Biochemistry, Medical University of Wroclaw, Chalubinskiego 10, 50-368, Wroclaw, Poland.

出版信息

Macromol Biosci. 2017 May;17(5). doi: 10.1002/mabi.201600356. Epub 2017 Jan 17.

Abstract

The authors examine properties of daunorubicin (DNR)-loaded oil-core multilayer nanocapsules prepared via layer-by-layer approach with different polyelectrolyte (PE) coatings such as a standard one (containing polysodium 4-styrenesulphonate/poly(diallyldimethyl-ammonium) chloride) and a polysaccharide-based shell (dextran/chitosan), in regard to the outer layer of poly-l-glutamic acid (PGA) grafted with polyethylene glycol (PGA-g-PEG). The nanocarriers are obtained on a cationic nanoemulsion template (stabilized by dicephalic-type surfactant, N,N-bis[3,30-(trimethylammonio)propyl]-dodecanamide dimethylsulfate) and layered with the PE shell of different thicknesses resulting in average size of 150 nm in diameter (as shown by dynamic light scattering, scanning electron microscopy and cryogenic-transmission electron microscopy, and atomic force microscopy). The nanocapsules demonstrate efficient DNR encapsulation and its sustained release under physiological conditions or in the attendance of human serum albumin. The biocompatibility studies using colon carcinoma MC38 and macrophage P388D1 cell lines as well as human erythrocytes reveal that surface charge and outer PE layer type determine nanocarrier features that control their biological activity: protein adsorption, cellular internalization and localization, induction of apoptosis, and hemolytic activity. The investigations indicate that polysaccharide-coated nanocapsules present a considerable potential for application as efficient DNR delivery systems in chemotherapy of colon cancer as an alternative to nanocarriers with PEG-ylated shell.

摘要

作者研究了通过逐层方法制备的载有柔红霉素(DNR)的油核多层纳米胶囊的性质,这些纳米胶囊具有不同的聚电解质(PE)涂层,例如标准涂层(包含聚4-苯乙烯磺酸钠/聚二烯丙基二甲基氯化铵)和基于多糖的壳层(葡聚糖/壳聚糖),并涉及接枝了聚乙二醇的聚-L-谷氨酸(PGA-g-PEG)外层。纳米载体是在阳离子纳米乳液模板(由双头型表面活性剂N,N-双[3,30-(三甲基铵基)丙基]-十二烷酰胺硫酸二甲酯稳定)上获得的,并包覆有不同厚度的PE壳层,直径平均为150 nm(动态光散射、扫描电子显微镜、低温透射电子显微镜和原子力显微镜显示)。纳米胶囊在生理条件下或在人血清白蛋白存在的情况下表现出高效的DNR包封及其持续释放。使用结肠癌细胞系MC38和巨噬细胞P388D1以及人红细胞进行的生物相容性研究表明,表面电荷和外层PE层类型决定了控制其生物活性的纳米载体特征:蛋白质吸附、细胞内化和定位、凋亡诱导以及溶血活性。研究表明,多糖包被的纳米胶囊作为结肠癌化疗中高效DNR递送系统具有相当大的应用潜力,可替代具有聚乙二醇化壳层的纳米载体。

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