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用于药物控释的远程触发支架

Remotely triggered scaffolds for controlled release of pharmaceuticals.

作者信息

Roach Paul, McGarvey David J, Lees Martin R, Hoskins Clare

机构信息

Guy Hilton Research Centre, Institute of Science and Technology in Medicine, Keele University, Keele, ST4 7QB, UK.

出版信息

Int J Mol Sci. 2013 Apr 19;14(4):8585-602. doi: 10.3390/ijms14048585.

Abstract

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold.

摘要

四氧化三铁-金杂化纳米粒子(HNPs)在生物医学应用中展现出越来越大的潜力,如影像引导的刺激响应药物递送。将HNPs的独特性质融入热响应支架中,对未来生物医学应用具有巨大潜力。在此,我们成功制备了基于热响应性聚(N-异丙基丙烯酰胺)(pNiPAM)的智能支架。发现当用短激光脉冲照射时能提供局部加热触发的纳米粒子可引发本体聚合物收缩的远程控制。采用湿化学沉淀法合成金包覆的氧化铁纳米粒子,随后进行电化学包覆。在用烯丙基甲基硫醚、巯基癸烷、半胱胺和聚(乙二醇)硫醇对粒子进行后续功能化以增强稳定性之后,通过活/死染色以及通过乳酸脱氢酶(LDH)定量进行细胞膜完整性研究来确定详细的生物安全性。聚乙二醇包覆的HNPs在暴露于7F2细胞时未显示出显著的细胞毒性作用或不良细胞反应(p < 0.05),并被用于支架构建。使用调Q Nd:YAG激光研究了pNiPAM-HNP复合支架作为热触发系统的潜力。这些研究表明,由于内部结构加热,在极短的照射时间(数秒)后,HNPs的加入导致支架变形。我们的数据突出了这些杂化支架构建体在药物递送中的应用潜力,以亚甲蓝作为在支架远程结构变化过程中释放的模型药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c60/3645763/e3c93390757c/ijms-14-08585f1.jpg

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