Photodynamic Therapy via Implantable Microsystems for Cancer Treatment

患者研究项目假设，通过为世界上第一个原位光动力疗法（PDT）创建可植入微系统，可以彻底改变膀胱癌的时间关键性和治愈性治疗。通过在无线植入式微系统中对光活性、多孔和高表面积聚合物进行复杂的优化和整合，我们的目标是提供原位单线态氧，以增强肿瘤细胞的杀伤作用，无论是作为单一疗法还是与放射疗法相结合。这项革命性的新技术有可能解决与晚期发现，有限的治疗选择和高死亡率相关的膀胱癌未满足的临床需求。目前PDT的临床应用受到光敏剂在健康正常组织中的相关摄取的阻碍，当暴露于光时导致毒性，并且难以将光源穿透到更深的光敏化癌组织以激活治疗。无线供电的可植入微系统针对这两个主要限制，因为其被设计为在临床感兴趣的点处实现重复的单线态氧，这是因为并入了微发光二极管（micro-LED）。单线态氧的受控输送将使恶性细胞对辐射敏感，微系统主体被用作放射治疗对准的植入标记。这一创造性概念的延伸，即利用纳米工程层次结构中的智能功能材料与先进的无线设计相结合，是功能化聚合物涂层可用于癌症复发前兆检测的治疗后监测。这将通过一种低成本的使能技术提供一种治愈性治疗途径，以提高生存率，减少患者副作用，并为癌症患者创造一种新的治疗后支持选择。PATIENT项目的潜在回报是，我们将创造一种新的癌症治疗方法，解决未满足的临床需求，提高膀胱癌患者的生存率。通过外部激励系统激活医疗植入物也将积极影响等待时间，这在癌症患者的高后果医疗干预中至关重要。纳米工程微系统中的功能化聚合物将提供持续的医疗和治疗后护理，以检测癌症复发的前兆。除了癌症治疗，英国各地的卫生委员会正面临前所未有的压力，英国国民保健服务（NHS）等候名单上有600多万患者。COVID-19加剧了英国医疗服务面临的挑战。该项目中的基础学习，可以启动新一代的网络物理医疗助理，利用植入式微系统，提供负担得起的护理点治疗和诊断，支持医疗保健提供的可访问性（公平性），降低不断上升的NHS成本，支持劳动力弹性由于需求水平，并建立应对老龄化社会需求的能力，长期护理需求不断增长。

The PATIENT research project hypothesizes that time-critical and curative treatment for bladder cancer can be revolutionised by creating implantable microsystems for a world-first in-situ photodynamic therapy (PDT). Through the complex optimisation and integration of photoactive, porous, and high surface area polymers within a wireless implantable microsystem, we aim to deliver in-situ Singlet Oxygen to enhance tumour cell kill either as a monotherapy or in combination with radiotherapy. This revolutionary new technology has the potential to address the unmet clinical needs of Bladder Cancer associated with late detection, limited treatment options, and a high mortality rate. Current clinical utilisation of PDT is impeded by the associated uptake of the photosensitizer in healthy normal tissue leading to toxicity when exposed to light and difficulties in penetrating the light source to deeper photosensitised cancerous tissues to activate the treatment. The wirelessly powered implantable microsystem targets these two primary limitations as it is designed to enable repeated singlet oxygen at the point of clinical interest because of the incorporation of a micro-light-emitting diode (micro-LED). The controlled delivery of singlet oxygen will sensitise malignant cells to radiation, with the microsystem body being used as an implanted marker for radiotherapy alignment. An extension of this creative concept, that exploits smart, functional materials within a nanoengineering hierarchy coupled with advanced wireless design is that functionalised polymer coatings can be used for post-treatment monitoring of precursor detection of cancer reoccurrence. This will provide a curative treatment pathway via a low-cost enabling technology to improve survival rates, reduce patient side-effects, and create a new post-treatment support option for cancer patients.The potential reward of the PATIENT project is that we will create a new cancer treatment that addresses an unmet clinical need, improving the survival rates for bladder cancer patients. The activation of the medical implant via an external excitation system will also positively impact waiting times, which are vital in high consequence medical interventions for cancer patients. The functionalised polymers in the nanoengineered microsystem will provide both ongoing medical treatment and post-treatment care to detect cancer reoccurrence precursors. Beyond cancer treatment, health boards across the UK are under unprecedented pressure, as evident with over 6 million patients on NHS England waiting lists. COVID-19 has exacerbated the challenges facing UK healthcare provision. The foundational learning within this project, could initiate a new generation of cyber-physical medical assistants that utilise implantable microsystems, providing affordable point of care treatment and diagnostics supporting accessibility (equity) in healthcare provision, reduction of escalating NHS costs, supporting workforce resilience due to levels of demand, and creating a responsive capability to the demands of an aging society with growing long-term care requirements.