Bioorthogonal Gold Chemistry to Explore Novel Biomedical Applications

用于治疗疼痛的药物，例如坐骨神经痛或腰酸背痛，可能会引起严重的副作用，以至于患者被迫在症状（头晕、恶心、便秘、抑郁）和疼痛之间做出选择。这些副作用在神经系统（如大脑）中很常见，因为它们也是治疗焦虑和癫痫等其他疾病的方法。这种未被满足的临床需求要求开发更智能的药物，只在需要的地方起作用，针对疼痛的目标部位，对身体的其他部位没有影响。为了提供一种更安全、更有效的策略来治疗局部疼痛，我们设计了一种新的方法，通过化学方法使药物失效，使它们不再起作用。它们可以用黄金重新激活，黄金将被封装在一个小装置中，植入疼痛部位或脊柱。口服给药的非活性药物前体只会在与黄金装置相互作用时在疼痛部位变得“活跃”，副作用最小。这项技术是基于爱丁堡大学爱丁堡癌症研究中心开创的一项新策略，该策略可以完全控制治疗的作用。为了发展这一概念，我们首先需要找到最有效的方法使药物失活，并防止它们产生任何影响，然后测试它们在生物环境中被黄金重新激活的速度和效率。我们还需要研究保护黄金免受身体攻击的最佳方法，以防止其激活药物的能力随着时间的推移而减弱。三分之一到一半的英国人患有慢性疼痛，但随着人口老龄化，这一数字预计会增加。由坐骨神经痛引起的神经痛以及其他问题，包括糖尿病、感染和癌症，影响了超过8%的英国人口。例如，患有多发性硬化症、脑瘫、脊髓损伤和复杂局部疼痛综合征的患者将成为这种治疗的受益者，而且有可能将这项技术扩展到许多其他慢性疾病，如帕金森病。由于它的新颖性，它将对制药行业产生重大影响，反过来，通过改善痛苦患者的生活质量，对NHS和英国乃至全世界的人们产生重大影响。

Drugs used in the treatment of pain, for instance sciatica or hernia back pain, can cause serious unwanted side-effects to such a level that patients are forced to choose between symptoms (dizziness, sickness, constipation, depression) and the pain. These side effects are common in the nervous system (e.g. the brain) because they are also treatments for other conditions like anxiety and epilepsy. This unmet clinical need calls for the development of smarter medications that only work where needed, that target site of pain with no effect on the rest of the body.To provide a safer and more effective strategy to treat localised pain, we have devised a new approach that chemically-deactivates the drugs, so they no longer have an effect. They can be reactivated with the use of gold, which would be encapsulated in a small device and implanted at the site of pain or the spine. Orally-given inactive drug precursors will only become "active" at the pain site upon interaction with the gold device, with minimal side effects. This technology is based on a novel strategy pioneered at the Edinburgh Cancer Research Centre at the University of Edinburgh that enables full control over where the therapy takes action.In order to develop this concept, we need to first find the most effective way to deactivate the drugs, and prevent them from causing any effect, then test how quickly and efficiently they are reactivated by the gold in a biological setting. We also need to research the best way to protect the gold from attack by the body to prevent the dulling of its ability to activate the drugs over time.Between one-third and one-half of the UK suffer from chronic pain, but this figure is expected to increase with an ageing population. Nerve pain due to sciatica and other issues including diabetes, infection and cancer, affects over 8% of the UK population. Patients suffering from multiple sclerosis, cerebral palsy, spinal cord injury and complex regional pain syndrome, for example, would be the beneficiaries of this treatment, and there is potential to expand the technology to many other chronic diseases such as Parkinson's. Due to its novelty, it will make a major impact in the pharmaceutical sector and, in turn, to the NHS and people of the UK and worldwide by improving the quality-of-life of people suffering from pain.