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JACS:开发出可以检测炎症反应的新型纳米颗粒

来源:生物谷 2012-09-19 22:15

2012年9月19日 讯 /生物谷BIOON/ --炎症是人类许多疾病,包括从感染到神经变性疾病等疾病的一个重要标志物,组织中的化学平衡被打破会导致机体活性氧(ROS)的积累,如过氧化氢的积累,这将最终促使机体发生氧化性应激和相关的毒性效应。

尽管一些ROS对于细胞信号通路和机体的防御机制非常重要,但是ROS也是许多疾病的指示物,如心血管功能障碍等疾病。一种非侵入型的可以检测过氧化氢或者其它ROS的方法或许为研究者提供了一种检测机体炎症的新方法,这样的方法也可以帮助科学家有选择性地将药物运送至炎症靶点。

指导这项研究的研究者,来自加州大学的副教授Adah Almutairi发明出了一种降解性高分子(degradable polymer),其对于低水平的过氧化氢相当敏感,可以对其进行敏感性监测。相关研究刊登在了近日的国际杂志the Journal of the American Chemical Society上。

这种降解性高分子多聚体胶囊,或者称为纳米颗粒可以被巨噬细胞和中性白细胞吞噬,然后运输到炎症靶位,随后当炎症细胞产生过氧化氢时,纳米颗粒就会释放内容物来作用于炎症靶细胞。

研究者Almutairi表示,这是我们首次进行的生物相容性的途径来对氧化压力和炎症产生反应。因为这种纳米颗粒胶囊可以被快速降解,而且在其检测到过氧化氢时可以释放内容物,因此,这种胶囊可以将靶向药物运输至疾病的组织来治疗疾病。

研究者目前正在动脉粥样硬化模型中进行这种新型方法的测试,相关的研究成果由美国国家卫生研究院创新奖等资助。(生物谷Bioon.com)

编译自:Nanoparticles Detect Biochemistry of Inflammation

Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide

Caroline de Gracia Lux , Shivanjali Joshi-Barr , Trung Nguyen , Enas Mahmoud , Eric Schopf , Nadezda Fomina , and Adah Almutairi *

Oxidative stress is caused predominantly by accumulation of hydrogen peroxide and distinguishes inflamed tissue from healthy tissue. Hydrogen peroxide could potentially be useful as a stimulus for targeted drug delivery to diseased tissue. However, current polymeric systems are not sensitive to biologically relevant concentrations of H2O2 (50–100 μM). Here we report a new biocompatible polymeric capsule capable of undergoing backbone degradation and thus release upon exposure to such concentrations of hydrogen peroxide. Two polymeric structures were developed differing with respect to the linkage between the boronic ester group and the polymeric backbone: either direct (1) or via an ether linkage (2). Both polymers are stable in aqueous solution at normal pH, and exposure to peroxide induces the removal of the boronic ester protecting groups at physiological pH and temperature, revealing phenols along the backbone, which undergo quinone methide rearrangement to lead to polymer degradation. Considerably faster backbone degradation was observed for polymer 2 over polymer 1 by NMR and GPC. Nanoparticles were formulated from these novel materials to analyze their oxidation triggered release properties. While nanoparticles formulated from polymer 1 only released 50% of the reporter dye after exposure to 1 mM H2O2 for 26 h, nanoparticles formulated from polymer 2 did so within 10 h and were able to release their cargo selectively in biologically relevant concentrations of H2O2. Nanoparticles formulated from polymer 2 showed a 2-fold enhancement of release upon incubation with activated neutrophils, while controls showed a nonspecific response to ROS producing cells. These polymers represent a novel, biologically relevant, and biocompatible approach to biodegradable H2O2-triggered release systems that can degrade into small molecules, release their cargo, and should be easily cleared by the body.

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