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基于糖原的新型杂合共聚物载体系统的生物学特性研究

Biological characterization of a novel hybrid copolymer carrier system based on glycogen.

机构信息

Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958/9, 140 21, Prague 4, Czech Republic.

Department of Physiology, Faculty of Science, Charles University in Prague, Viničná 7, 128 44, Praha 2, Czech Republic.

出版信息

Drug Deliv Transl Res. 2018 Feb;8(1):73-82. doi: 10.1007/s13346-017-0436-x.

Abstract

The effective drug delivery systems for cancer treatment are currently on high demand. In this paper, biological behavior of the novel hybrid copolymers based on polysaccharide glycogen were characterized. The copolymers were modified by fluorescent dyes for flow cytometry, confocal microscopy, and in vivo fluorescence imaging. Moreover, the effect of oxazoline grafts on degradation rate was examined. Intracellular localization, cytotoxicity, and internalization route of the modified copolymers were examined on HepG2 cell line. Biodistribution of copolymers was addressed by in vivo fluorescence imaging in C57BL/6 mice. Our results indicate biocompatibility, biodegradability, and non-toxicity of the glycogen-based hybrid copolymers. Copolymers were endocyted into the cytoplasm, most probably via caveolae-mediated endocytosis. Higher content of oxazoline in polymers slowed down cellular uptake. No strong colocalization of the glycogen-based probe with lysosomes was observed; thus, it seems that the modified externally administered glycogen is degraded in the same way as an endogenous glycogen. In vivo experiment showed relatively fast biodistribution and biodegradation. In conclusion, this novel nanoprobe offers unique chemical and biological attributes for its use as a novel drug delivery system that might serve as an efficient carrier for cancer therapeutics with multimodal imaging properties.

摘要

用于癌症治疗的有效药物输送系统目前需求量很大。本文对基于多糖糖原的新型杂化共聚物的生物学行为进行了表征。共聚物通过荧光染料进行了修饰,用于流式细胞术、共聚焦显微镜和体内荧光成像。此外,还研究了恶唑啉接枝对降解速率的影响。在 HepG2 细胞系上研究了修饰共聚物的细胞内定位、细胞毒性和内化途径。通过在 C57BL/6 小鼠体内荧光成像研究了共聚物的体内分布。我们的结果表明,基于糖原的杂化共聚物具有生物相容性、可生物降解性和低毒性。共聚物被内吞到细胞质中,很可能是通过胞吞作用。聚合物中恶唑啉含量的增加减缓了细胞摄取。未观察到基于糖原的探针与溶酶体的强烈共定位;因此,似乎修饰后的外源性给予的糖原以与内源性糖原相同的方式降解。体内实验显示出相对较快的体内分布和生物降解。总之,这种新型纳米探针具有独特的化学和生物学特性,可作为一种新型药物输送系统,具有多模式成像特性,可作为癌症治疗的有效载体。

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