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一种自组装可交联透明质酸纳米凝胶的生物相容性

Biocompatibility of a Self-Assembled Crosslinkable Hyaluronic Acid Nanogel.

作者信息

Pedrosa Sílvia Santos, Pereira Paula, Correia Alexandra, Moreira Susana, Rocha Hugo, Gama Francisco Miguel

机构信息

Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Campus de Gualtar, University of Minho, Braga, 4710-05, Portugal.

Institute of Molecular and Cell Biology, Rua Campo Alegre, Porto, 4099-003, Portugal.

出版信息

Macromol Biosci. 2016 Nov;16(11):1610-1620. doi: 10.1002/mabi.201600221. Epub 2016 Jul 26.

Abstract

Hyaluronic acid nanogel (HyA-AT) is a redox sensitive crosslinkable nanogel, obtained through the conjugation of a thiolated hydrophobic molecule to the hyaluronic acid chain. Engineered nanogel was studied for its biocompatibility, including immunocompatibility and hemocompatability. The nanogel did not compromise the metabolic activity or cellular membrane integrity of 3T3, microvascular endothelial cells, and RAW 264.7 cell lines, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase release assays. Also, we didn't observe any apoptotic effect on these cell lines through the Annexin V-FITC test. Furthermore, the nanogel cell internalization was analyzed using murine bone marrow derived macrophages, and the in vivo and ex vivo biodistribution of the Cy5.5 labeled nanogel was monitored using a non-invasive near-infrared fluorescence imaging system. The HyA-AT nanogel exhibits fairly a long half-live in the blood stream, thus showing potential for drug delivery applications.

摘要

透明质酸纳米凝胶(HyA-AT)是一种对氧化还原敏感的可交联纳米凝胶,通过将硫醇化疏水分子与透明质酸链共轭获得。对工程化纳米凝胶的生物相容性进行了研究,包括免疫相容性和血液相容性。通过3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐和乳酸脱氢酶释放试验测定,该纳米凝胶不影响3T3、微血管内皮细胞和RAW 264.7细胞系的代谢活性或细胞膜完整性。此外,通过膜联蛋白V-异硫氰酸荧光素试验,我们未观察到对这些细胞系有任何凋亡作用。此外,使用小鼠骨髓来源的巨噬细胞分析了纳米凝胶的细胞内化,并使用非侵入性近红外荧光成像系统监测了Cy5.5标记纳米凝胶的体内和体外生物分布。HyA-AT纳米凝胶在血流中表现出相当长的半衰期,因此显示出在药物递送应用中的潜力。

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