Photodynamic Therapy via Implantable Microsystems for Cancer Treatment
Lead Research Organisation:
University of Glasgow
Department Name: School of Engineering
Abstract
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.
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.
| Description | This research has led to several key advancements. First, we generated significant new knowledge by demonstrating the potential of wirelessly powered photodynamic therapy (PDT) implants for bladder cancer treatment. Our findings highlight the effectiveness of PA-ABT and associated polymeric photosensitizers based photodynamic polymers in inducing cancer cell death, laying the groundwork for future clinical applications. Second, we developed new research methods, including confocal laser scanning microscopy (CLSM) for urothelial imaging and 3D modeling using Autodesk Maya, which enabled precise estimations of cellular coverage under the LED. These methods provide a valuable framework for optimizing light-based therapies in other biomedical applications. Also, this study identified important new research questions, particularly regarding the long-term effects of repeat PDT exposures and the scalability of wireless implants for broader oncological applications. These findings will guide future investigations into dose optimization, energy efficiency, and treatment efficacy. Lastly, this project has fostered new interdisciplinary collaborations, bringing together oncologists, bioengineers, and material scientists. This has enhanced research capabilities through specialist training in nanoengineering, biomedical imaging, and wireless power transfer, creating a strong foundation for future innovation in implantable medical technologies. I would like to provide an update on the progress of our recent publications. I am pleased to share that four of our papers are progressing well, with one having undergone revisions and successfully resubmitted. Key Achievements: These publications under review represent significant progress in our research for Photodynamic Therapy project (PATIENT). Paper 1. In Vitro Assessment of Benzothiadiazole-Based Photoactive Polymers Against Ovarian, Prostate and Bladder Cancer Cell Lines for Photodynamic Therapy. The aim of this study is to explore whether PA-ABT and associated polymeric photosensitizers show efficacy when targeted against human cancer cell lines in vitro. Paper 2. Fabrication of Laser-Ablated Flexible Wireless Microsystem for Implantable Photodynamic Therapy in Bladder Cancer Treatment. In this work, we successfully designed, manufactured and characterized a laser-ablated flexible wireless microsystem for implantable PDT. Paper 3. Light-Based Bladder Cancer Therapy: Photodynamic Evaluation of Polymer-Based Photosensitizers to Show Efficacy When Targeted Against Human Cancer Cell-Lines in vitro and 3D Cellular Imaging. In this study, the prototype device has demonstrated promising performance in its initial evaluation, effectively inhibiting cancer cell growth with a single exposure to 520 nm light. T Paper 4. This is a review-based paper on advancing bladder cancer treatment: A Comprehensive Review of Photodynamic Therapy and Smart Implant Technologies with Laser-Ablated Flexible Wireless Microsystem. |
| Exploitation Route | The outcomes of this funding could be taken forward and put to use by others in several impactful ways: The findings could contribute to the development of wireless photodynamic therapy (PDT) implants, leading to preclinical and clinical trials for bladder cancer and potentially other malignancies. Researchers can build on the study to optimize polymer-based photosensitizers, improving their efficiency, biocompatibility, and selectivity for targeted cancer treatments. |
| Sectors | Education Healthcare |
| URL | https://glasgowcityofscienceandinnovation.com/glasgow-engineers-win-iet-innovation-award-for-wireless-powered-therapeutics-research/ |
| Description | My findings have been widely used with different scientific audiences including future healthcare technologies. Events Attended: • Digital health technologies for precision medicine: a seminar and workshop/event SYMBIOSIS: Healthcare bioimaging and biosensing exchange. • College of Science and Engineering Research Introductions Zoomposium#34. • CENSIS annual conference, Technology Summit CENSIS and DHVL Living Lab (University of Glasgow) workshop. • Registered for the College of Science and Engineering (COSE) Early Career Development Programme (ECDP). • Invitation from Heriot-Watt University to AIMday HealthTech to attend an online talk. • Attended a seminar by Dr Richard Evans, Programme Manager for Clinical Sciences & Rare Diseases at the Medical Research Council (MRC). The MRC is a part of UK Research and Innovation (UKRI) and their mission is to improve human health through world-class medical research. • Attended a number of connecting people impact events at University of Glasgow. • Attended a networking workshop around the theme of Healthcare Technologies, co-organised by the Division of Biomedical Engineering (University of Glasgow) and the Department of Biomedical Engineering (University of Strathclyde). Meetings and Collaboration: • I have Engaged regularly with different group meetings with rich discussions and extensive information sharing are critical for effective scientific communications, especially technical discussions will lead to more effective work environment between different groups and this will also allow us to discuss important technical/scientific ideas. This also help us on what methodological expertise do different people bring, explore different ideas, further collaboration, knowledge or expertise might we be missing. A special focus would be around who's doing what work, how the work is progressing and obviously understanding each other's needs and challenges and try to resolve these challenges as a team. • An invited speaker to present our work on Photodynamic Therapy at Living Lab Healthcare Innovation Conference 2023. The Living Laboratory College of Medical Veterinary and Life Sciences University of Glasgow (Queen Elizabeth Hospital). • Held a meeting with Dr Euan Head of Scientific Services, Photobiology Unit at Ninewells hospital, Dundee to discuss future collaboration between Ninewells hospital, Dundee and University of Glasgow. This meeting involved Dr Euan and his postdoc/Ph.D. students; part of the discussion was how we can improve future healthcare devices for Photodynamic Therapy. We discussed building some collaborative links which could support our ongoing projects and potentially inform future proposals wherein we can leverage the clinical and/or cancer expertise in Ninewells/UoD. • We also discussed that over the past couple of years it has become clear to us in the Scottish PDT Centre that there is a growing and diverse interest in Photodiagnostic & Photodynamic Therapy research in Scotland. We agreed the time is right to hold a networking event for all of the PDT researchers in Scotland, to share knowledge and to raise awareness of the work being undertaken. We proposed this one-day event take place in Dundee in the first half of 2024. Also, discussed potential future collaboration between University of Glasgow and Ninewells hospital and University of Dundee. • Organised a networking event for all of the PDT researchers in Scotland (April 2024), to share knowledge and to raise awareness of the work being undertaken, this event was held in collaboration with Head of Scientific Services, Photobiology Unit at Ninewells hospital, Dundee. We discussed the growing interest in Photography Therapy research here in Scotland and maybe other parts of the UK and to give us the chance to share valuable knowledge and gather information about what other researchers in the field of Photodynamic Therapy. • Will be holding an organised a get together second event to share knowledge for future Photodynamic Therapy at University of Glasgow in the later part of the year (2025) • Made connection with Dr David Bajek and Dr Mingkai Wang at the Urology department, Ninewells hospital to help us test our Photodynamic protype device for bladder cancer. • Had discussions about MedTech in Healthcare Technology at UofG with Prof Sandy Cochran, Prof Julien Reboud and Dr Huabing Yin, this is an initiative to kickstart MedTech at University of Glasgow and Herriot watts University. • Had a number of meetings with Prof Robert Hadfield and Dr Vikas at ARC, university of Glasgow, these meetings were held to discuss instant collaboration for Photodynamic Therapy between the two departments here in Glasgow on the work of singlet oxygen luminescence setup and planning design of a fibre probe instrument for our NIH project with UPenn. We also discussed how the setup can be used for studies on different photosensitizers, tissue phantoms and potentially live cells, and the novel LEDs work I am working on and how this can be used to generate more date for Photodynamic Therapy and shared in put to our draft papers and analysis. And of course, proposed and welcomed their team to any new data we generate directly, or via our PhD, master's students etc. • Held a meeting with Dr Robert Edkins at the University of Strathclyde to discuss future collaboration between the two universities. Part of the meeting was to discuss how we can work together and use different photosensitisers for Photodynamic Therapy and we exchanged ideas on how we can improve future healthcare devices for Photodynamic Therapy. Also, discussed potential M.Sc. exchange project students. • I have arranged with a number of different groups including postdocs and Ph.D. students and their line mangers/supervisors once a month catch up friendly meetings (purely technical discussions) to allow the teams from different schools to have that valuable, open technical discussions and give us the opportunity to build upon our future Healthcare Technology capabilities and help us in the decision-making framework for future healthcare Photodynamic Therapy technologies. • Held a number of meetings with Dr Bhavani Yalagala at University of Glasgow for carried out some interesting collaboration between the two groups for the fabrication of flexible micro-system for Photodynamic Therapy, I have also discussed with him on how their group can contribute towards the microfabrication process for creating a Photodynamic Therapy device using different materials and microfabrication techniques and future prototype. • Held a number of meetings with Dr Mahmoud Wagih, Dr Ahmad Taha and his Ph.D. student at University of Glasgow for potential collaboration between the two groups. Also, discussed how their group can contribute towards the microelectronics design process for creating a Photodynamic Therapy protype device and how they can add their knowledge towards the microelectronics wireless journal paper section and include the bi-directional communication, i.e., controlling the LED (remotely) and reading data from the implant and the extraction of the data from the implant signals the start of the second stage of data transmission which involves fulfilling the goal of relaying the data to one or multiple locations for remote monitoring and decision making. • Had a number of meetings with Edinburgh Instruments, these meetings were held to discuss instant collaboration for Photodynamic Therapy and carried out some interesting work on to test our LED's device functionality and to investigate the generation of singlet oxygen using their luminescence probe instrument. • I had meeting with Dr Saydulla Persheyev at the University of St Andrews to discuss the possibility of joint collaboration between our department (University of Glasgow) and the University of St Andrews for the development of future Medical Devices for PDT. • I had meeting with Dr Karin Williams Translational Radiation Biology Wolfson Wohl Cancer Research Centre Institute of Cancer to discuss the possibility of joint collaboration between the two departments for the development of future Medical Devices for PDT. • On Thursday, 23 May 2024 I attended the Medical Device Manufacturing Centre MDMC Annual Conference. • I was an invited speaker to present our recent work on Photodynamic Therapy at Scientific Services, Photobiology Unit at Ninewells hospital, Dundee). • I have attended Healthcare Technologies DHVL Roadshow 5th August 2024 • I presented our work on Photodynamic Therapy at ASC Presentation Series at UoG • I have attended MVLS-CoSE collaboration in Advanced Diagnostics and Therapeutics 03rd September 2024 |
| First Year Of Impact | 2024 |
| Sector | Education,Healthcare |
| Description | Evaluation of photodynamic agents. |
| Organisation | University of Glasgow |
| Department | Physics and Astronomy Department |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We are bringing together researchers from the EPSRC project and a NIH funded photodynamic therapy project evaluating the role of |
| Collaborator Contribution | They have supported the development and characterisation of singlet oxygen luminescence analysis using a fibre probe instrument for singlet oxygen detection in partnership with Penn State University (USA). We are exploring how this tailored experimental setup can be used for studies on different photosensitizers, tissue phantoms and potentially live cells. We intend to explore how this device can also be used to characterize the performance of a microfabricated wireless PDT device. |
| Impact | The first outcome is a joint draft paper that will be submitted within 3 weeks to Wiley. |
| Start Year | 2023 |
| Description | Living Lab Healthcare Innovation Conference 2023 |
| Organisation | Queen Elizabeth University Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | Sharing our first set of experimental results involving the evaluation of photodynamic polymers and their performance in treating cancer cell lines for prostate, bladder and ovarian cancer. |
| Collaborator Contribution | The team at the Living Laboratory College of Medical Veterinary and Life Sciences University of Glasgow (Queen Elizabeth Hospital), are supporting through in-kind contribution further evaluation of different photodynamic agents and cancer cells lines as to increase the statistical base of photodynamic therapy analysis. |
| Impact | This partnership is multidisciplinary bringing together experimental therapeutics in cancer treatment, micro/Nano systems engineering and bioengineering. An outcome is a first draft of a journal paper which is going through final rounds of review prior to submission to Wiley : https://onlinelibrary.wiley.com/page/journal/21922659/homepage/productinformation.html |
| Start Year | 2023 |
| Description | Photobiology Unit at Ninewells hospital |
| Organisation | Ninewells Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have presented our preliminary results of the responses to singlet oxygen from photodynamic polymers to cancer cell lines - ovarian, bladder and prostate. Initially results indicate positive performance for certain cell lines. |
| Collaborator Contribution | Through in-kind collaboration we will explore features such as photobleaching , for certain photodynamic agents, and we will also present the microfabrication prototype with the surgical consultants. The consultants are affiliated with the Urology department, Ninewells hospital in relation to future bladder cancer combination or monotherapys. |
| Impact | Outcomes have involved joint engagement event in 2023 and a planned photodynamic therapy network event in Dundee in 2024. |
| Start Year | 2023 |
| Description | An invited speaker presentation (Dr Mansour) to present our work on Photodynamic Therapy at Living Lab Healthcare Innovation Conference 2023 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was an interdisciplinary event to bring medical practitioners and researchers, into discussions with researchers from engineering and physical sciences. It was highlighting the approaches, models, methods etc of the different disciplines and how system engineering methods can create new treatment options for cancer based on overcoming known limitations of accepted treatments. It was attended by over 100+ researchers and medical professionals. |
| Year(s) Of Engagement Activity | 2023 |
| Description | An invited speaker presentation (Dr Mansour) to present our work on Photodynamic Therapy at Photobiology Unit at Ninewells hospital, Dundee and University of Glasgow 2023 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Study participants or study members |
| Results and Impact | This was an interdisciplinary event to bring medical practitioners and researchers, into discussions with researchers from engineering and physical sciences. It was highlighting the approaches, models, methods etc of the different disciplines and how system engineering methods can create new treatment options for cancer based on overcoming known limitations of accepted treatments. It was attended by over 10+ researchers. |
| Year(s) Of Engagement Activity | 2023 |
| Description | I presented our work on Photodynamic Therapy at ASC Presentation Series at UoG 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was an interdisciplinary event to bring medical practitioners and researchers, into discussions with researchers from engineering and physical sciences. This was for different disciplines and how system engineering methods can create new treatment options for cancer based on overcoming known limitations of accepted treatments. It was attended by over 100+ researchers and medical professionals. |
| Year(s) Of Engagement Activity | 2024 |