Medical Nitric Oxide-Releasing Nanoporous Organic Polymers as Topical Therapeutic Agents

医用释放一氧化氮的纳米多孔有机聚合物作为局部治疗剂

• 批准号: EP/M027295/1
• 负责人: Bo Xiao
• 金额: $ 12.67万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM027295%2F1
• 关键词: Medical; Nitric; Oxide; Releasing; Nanoporous

The chronic wound treatment is a particularly challenging clinical problem, which has been highlighted as unmet need of the National Health Service (NHS) patients by the United Kingdom's National Institute for Health Research (NIHR) in 2013. In fact, currently no efficacious methods exist. The chronic wounds mostly leg ulcers, pressure ulcers, and diabetic foot ulcers adversely affect patients' quality of life, costs the NHS £2-3 billion annually for wound treatments. Therefore, if we develop a simple and effective method which can accelerate chronic wound healing and reduce the treatment cost, which would be very attractive. Nitric oxide (NO), a well-known air pollutant produced from combustion processes, has been found to play important roles as a regulator and mediator of numerous processes in the nerve, immune, and cardiovascular systems. These findings encourage pathways to utilise the beneficial functions of NO gas to tackle a variety of challenging medical issues, one of which is the treatment of chronic wounds. Wound care research has indicated the outstanding effectiveness of gaseous NO in accelerating chronic wound healing by in vitro and in vivo studies. However, delivering NO gas is very challenging task because of its gaseous nature and toxicity. This requires developing a specific 'vehicle' capable of carrying the desired amounts of NO to the local wound sites and discharging the NO in a safe and controllable manner. To address this challenge, we propose a new method based on nanoporous porous organic polymer (POP) as new generation of gaseous nitric oxide delivery 'vehicle' to fulfil our ambitions. POPs are a new class of nanoporous materials which have been widely investigated in recent years, for example the conjugated microporous polymers (CMPs) developed by Cooper et al. The facile synthesis of POP materials is by assembling organic molecular building blocks into two or three dimensional porous networks through carbon-carbon coupling or cyclic condensation reactions. The POPs possess diverse porous structures and functionalities as well as relatively high chemical stability, which have attracted increasing research interests in gas adsorption/storage/separation and heterogeneous catalysis, and show promising potential for drug delivery for therapeutics. In this project, we will explore new POP materials suitable for storing high capacities of NO gas. With POPs' reacting with NO gas to form diazeniumdiolate structures in the frameworks, the NO gas is expected to be 'chemically compressed' in the porous networks. In this manner, high capacity of NO storage is reached, which ensures a controllable delivery of a desired amount of NO to the local wound sites. Furthermore, the quantity of NO stored in the POPs will be optimised through adjusting the concentration of active functionalities and the NO loading conditions. The NO releasing characteristic profiles will be adjusted through judiciously choosing molecular building blocks and synthesis conditions to tune the pore size and the hydrophobicity/hydrophilicity of frameworks. We will systematically characterise the POP material structures, analyse the stored NO species and simulate the NO releasing kinetics. Relevant information obtained will be used for understanding the effects of POP structures , properties and synthesis conditions on the formation of diazeniumdiolates, so as to assess the performance of different POP materials, and optimise the material formulation and synthesis conditions. The results obtained from this project will become the foundations for manufacturing prototype therapeutic products in the future. By the end of this project, it is anticipated to develop a new promising NO gas delivery technology targeted for accelerating chronic wound healing.

慢性伤口治疗是一个特别具有挑战性的临床问题，2013年，英国国家健康研究所（NIHR）将其作为国民健康服务（NHS）患者未满足的需求进行了强调。事实上，目前还没有有效的方法。慢性伤口主要是腿部溃疡、压力性溃疡和糖尿病足溃疡，对患者的生活质量产生不利影响，NHS每年花费20 - 30亿英镑用于伤口治疗。因此，如果能开发出一种简单有效的方法，既能加速慢性创面的愈合，又能降低治疗成本，将是非常有吸引力的。一氧化氮（NO）是一种由燃烧过程产生的众所周知的空气污染物，已被发现在神经、免疫和心血管系统中作为许多过程的调节剂和介体发挥重要作用。这些发现鼓励人们利用NO气体的有益功能来解决各种具有挑战性的医疗问题，其中之一就是治疗慢性伤口。伤口护理研究已经通过体外和体内研究表明气态NO在加速慢性伤口愈合中的显著效果。然而，由于其气态性质和毒性，输送NO气体是非常具有挑战性的任务。这需要开发一种特定的“载体”，其能够将所需量的NO携带到局部伤口部位，并以安全和可控的方式释放NO。为了应对这一挑战，我们提出了一种新的方法，基于纳米多孔多孔有机聚合物（POP）作为新一代的气态一氧化氮输送“车辆”，以实现我们的野心。POP是近年来研究较多的一类新型纳米多孔材料，例如库珀等人开发的共轭微孔聚合物（CMPs）。POP材料的简单合成是通过碳-碳偶联或环缩合反应将有机分子结构单元组装成二维或三维多孔网络。有机污染物具有多样的多孔结构和功能，以及较高的化学稳定性，在气体吸附/储存/分离和多相催化等方面具有广泛的应用前景。在本项目中，我们将探索适用于储存高容量NO气体的新型POP材料。随着POP与NO气体反应在骨架中形成diazeniumdiolate结构，NO气体有望在多孔网络中被“化学压缩”。以这种方式，达到了NO储存的高容量，这确保了所需量的NO向局部伤口部位的可控递送。此外，通过调节活性官能团的浓度和NO负载条件，将优化存储在POP中的NO的量。NO释放特性曲线将通过明智地选择分子构建块和合成条件来调节孔径和骨架的疏水/亲水性来调节。我们将系统地研究POP材料的结构，分析储存的NO物种，并模拟NO释放动力学。所获得的相关信息将用于了解持久性有机污染物的结构、性质和合成条件对二醇二氮烯鎓形成的影响，从而评估不同持久性有机污染物材料的性能，优化材料配方和合成条件。本研究成果将为未来治疗产品的研制奠定基础。到该项目结束时，预计将开发一种新的有前途的NO气体输送技术，旨在加速慢性伤口愈合。

项目成果

Functionalised solids delivering bioactive nitric oxide gas for therapeutic applications

• DOI: 10.1016/j.mtcomm.2017.07.007
• 发表时间: 2017-09-01
• 期刊: MATERIALS TODAY COMMUNICATIONS
• 影响因子: 3.8
• 作者: Gregg, Sharon T.;Yuan, Qingchun;Xiao, Bo
• 通讯作者: Xiao, Bo

Nanoporous and Functionalised Framework Materials for the Delivery of Bioactive Nitric Oxide

用于传递生物活性一氧化氮的纳米多孔和功能化框架材料

• 作者: Sharon Gregg (Smyth)

Light Triggered Nitric Oxide Release from N-Nitroso Porous Organic Polymers

N-亚硝基多孔有机聚合物光触发一氧化氮的释放

• 发表时间: 2017
• 作者: Gregg Sharon

Study of Porous Metal-Organic Frameworks (MOFs) for Active Pharmaceutical Ingredients (APIs) Delivery

用于活性药物成分 (API) 输送的多孔金属有机框架 (MOF) 的研究

• 发表时间: 2022
• 作者: Hungjui Chen

Functionalised Porous Organic Polymers for Bioactive Nitric Oxide Delivery

用于生物活性一氧化氮输送的功能化多孔有机聚合物

• 发表时间: 2017
• 作者: Sharon Gregg