Photodynamic Therapy via Implantable Microsystems for Cancer Treatment

PATIENT研究项目假设，通过为世界上第一个原位光动力治疗（PDT）创造可植入的微系统，可以彻底改变膀胱癌的时间关键和治愈性治疗。通过在无线可植入微系统中对光活性、多孔性和高表面积聚合物进行复杂的优化和集成，我们的目标是提供原位单线态氧，以增强肿瘤细胞的杀伤能力，无论是作为单一治疗还是与放疗联合使用。这项革命性的新技术有潜力解决膀胱癌未被满足的临床需求，这些需求与发现晚、治疗选择有限和死亡率高有关。目前PDT的临床应用受到健康正常组织中光敏剂的相关吸收的阻碍，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癌组织以激活治疗。无线供电的植入式微系统针对这两个主要的限制，因为它的设计是为了在临床感兴趣的点上实现重复的单线态氧气，因为它结合了一个微型发光二极管（micro-LED）。单线态氧的受控输送将使恶性细胞对辐射敏感，微系统体被用作放射治疗对准的植入标记物。这一创新概念的延伸是，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，功能化聚合物涂层可用于癌症复发前兆检测的后处理监测。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，减少患者的副作用，并为癌症患者创造一种新的治疗后支持选择。“病人”项目的潜在回报是，我们将创造一种新的癌症治疗方法，解决尚未满足的临床需求，提高膀胱癌患者的存活率。通过外部激发系统激活医疗植入物也将积极影响等待时间，这对于癌症患者的高后果医疗干预至关重要。纳米工程微系统中的功能化聚合物将提供正在进行的医疗和治疗后的护理，以检测癌症复发的前兆。除了癌症治疗之外，英国各地的健康委员会也面临着前所未有的压力，英国国家医疗服务体系（NHS）的候诊名单上有600多万患者。COVID-19加剧了英国医疗保健服务面临的挑战。在这个项目中的基础学习，可以启动新一代的网络物理医疗助理，利用可植入的微系统，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及性（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，并创建一个响应能力，以满足老龄化社会不断增长的长期护理需求。

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.