Periodic Reporting for period 4 - DYNACEUTICS (Remote control healing: Next generation mechano-nano-therapeutics)
Reporting period: 2023-07-01 to 2024-12-31
Promoting an active society is a key aim for prevention of many chronic conditions and reduction in age related illnesses. How do we ‘bottle’ an agonist like a drug which can mimic exercises without activity and influence or regulate mechano-sensors on the cell membrane in the same way? How do we control these receptors as a therapeutic target for treatment of disease and tissue repair? This project tackled this complex interdisciplinary question aiming to develop new nanotechnologies and protocols by which we can control cell mechanobiology remotely for multiple biomedical applications including targeted advanced therapies. Specifically, DYNACEUTICS developed a breakthrough platform technology, MICA – Magnetic Ion Channel Activation, where we remotely tag and activate the mechano- sensing cell membrane receptors sing magnetic particles.
DYNACEUTICS has defined protocols to control delivery, tracking and differentiation of therapeutic cells following delivery to patients using our novel MICA technology. The project has been split into multiple elements and in general progress has been excellent despite the issues of COVID lab closures. We are now at a stage where we have the confidence to start our translation towards first in man studies using data from the DYNACEUTICS project through a spin out, MICA Biosystems. Alongside this we have been exploring new and exciting avenues for receptor targeting using mechano-activation for immunotherapies, tendon repair and osteoarthritis.
DYNACEUTICS has defined protocols to control delivery, tracking and differentiation of therapeutic cells following delivery to patients using our novel MICA technology. The project has been split into multiple elements and in general progress has been excellent despite the issues of COVID lab closures. We are now at a stage where we have the confidence to start our translation towards first in man studies using data from the DYNACEUTICS project through a spin out, MICA Biosystems. Alongside this we have been exploring new and exciting avenues for receptor targeting using mechano-activation for immunotherapies, tendon repair and osteoarthritis.
Specifically, our project set out to and has achieved:
• Screened and identified mechano-receptor binding sites on stem and mature cells which can be tagged and activated. At the end of the project, we have identified the following receptor targets, ion channels such as TREK, TRPV4, PIezo1; growth factors, PDGF, Activin A and Wnt family receptors which can be targeted with the MICA platform.
• Functionalised and evaluated magnetic particles with tailored tagging strategiesfor tagging mechanoreceptors using single cell, 3D human disease models and in vivo preclinical models - We have identified and tested efficacy of multiple protocols for binding receptors which includes antibodies, aptamers, peptides. We have defined the use of patented aptamer approaches for tagging which can target specific regions. These studies have considered how magnetic fields can be used for controlling neuronal fibre outgrowth in 2D and 3D models (Bongaeraet et al 2020, In J. Mol. Sci.; Nahar et al 2025 Acta Biomaterialia). We have gained understanding as to how we can track our MNP tagged cells using current medical imaging modalities such as MRI. In this way, we can assess dosing of how many MNPS and MNP tagged cell survival. We followed the fate of our MNPs in an ovine model for short term evaluation with Orthopaedic clinicians from Nottingham Univ (Markides et al 2021, Cells) and longer term using MRI with Cambridge Univ (Kaggie et al 2020 Scientific Reports).
• Design and developed prototypes of external remote-control magnetic devices - we have used computational modelling and engineering principles to design a magnetic bioreactor for in vitro use, a magnetic chamber for animal studies, and a magnetic bandage for clinical use. In addition, we have carried out experimental and mathematical modelling investigating the use of magnetic fields to control delivery of our MNP tagged cells to the sites of repair with our collaborator, Professor Sarah Waters, Maths, Oxford (Yeo et al 2021, J. Roy. Soc. Inter).
• Created dynamic tissue assays for use in high-throughput drug screening and identification of dynamic relevant molecules which will expand new drug targets in pharmaceutical interventions. We have produced a new dynamic drug screening platform termed DYNASCREEN which is now being tested for CACO cell absorption assays for use by CROs and Pharma companies ( Unnithan et al IJMol Sci 2023). The assay can align to monolayer screening platforms, organoid cultures and organ on a chip applications. Follow on funding has included UK Innovate government funding to commercialise this platform
• Created clinically relevant treatment modalities for remote control healing –We have progressed our MICA platform through pre clinical rodent and large animal trials for 3 applications e.g. spinal fusion and bone repair, tendon repair and immunotherapy. In addition, we are working with clinical colleagues to identify challenges and opportunities for different clinical indications. We have now designed a clinical trial and optimised our protocols for moving forward into clinical trial for the treatment of spinal fusion.
This proposal has harnessed a unique opportunity to launch a new dynamic treatment platform, DYNACEUTICS, which we propose will extend the therapeutic horizon and provide a new form of remote-controlled healing.
• Screened and identified mechano-receptor binding sites on stem and mature cells which can be tagged and activated. At the end of the project, we have identified the following receptor targets, ion channels such as TREK, TRPV4, PIezo1; growth factors, PDGF, Activin A and Wnt family receptors which can be targeted with the MICA platform.
• Functionalised and evaluated magnetic particles with tailored tagging strategiesfor tagging mechanoreceptors using single cell, 3D human disease models and in vivo preclinical models - We have identified and tested efficacy of multiple protocols for binding receptors which includes antibodies, aptamers, peptides. We have defined the use of patented aptamer approaches for tagging which can target specific regions. These studies have considered how magnetic fields can be used for controlling neuronal fibre outgrowth in 2D and 3D models (Bongaeraet et al 2020, In J. Mol. Sci.; Nahar et al 2025 Acta Biomaterialia). We have gained understanding as to how we can track our MNP tagged cells using current medical imaging modalities such as MRI. In this way, we can assess dosing of how many MNPS and MNP tagged cell survival. We followed the fate of our MNPs in an ovine model for short term evaluation with Orthopaedic clinicians from Nottingham Univ (Markides et al 2021, Cells) and longer term using MRI with Cambridge Univ (Kaggie et al 2020 Scientific Reports).
• Design and developed prototypes of external remote-control magnetic devices - we have used computational modelling and engineering principles to design a magnetic bioreactor for in vitro use, a magnetic chamber for animal studies, and a magnetic bandage for clinical use. In addition, we have carried out experimental and mathematical modelling investigating the use of magnetic fields to control delivery of our MNP tagged cells to the sites of repair with our collaborator, Professor Sarah Waters, Maths, Oxford (Yeo et al 2021, J. Roy. Soc. Inter).
• Created dynamic tissue assays for use in high-throughput drug screening and identification of dynamic relevant molecules which will expand new drug targets in pharmaceutical interventions. We have produced a new dynamic drug screening platform termed DYNASCREEN which is now being tested for CACO cell absorption assays for use by CROs and Pharma companies ( Unnithan et al IJMol Sci 2023). The assay can align to monolayer screening platforms, organoid cultures and organ on a chip applications. Follow on funding has included UK Innovate government funding to commercialise this platform
• Created clinically relevant treatment modalities for remote control healing –We have progressed our MICA platform through pre clinical rodent and large animal trials for 3 applications e.g. spinal fusion and bone repair, tendon repair and immunotherapy. In addition, we are working with clinical colleagues to identify challenges and opportunities for different clinical indications. We have now designed a clinical trial and optimised our protocols for moving forward into clinical trial for the treatment of spinal fusion.
This proposal has harnessed a unique opportunity to launch a new dynamic treatment platform, DYNACEUTICS, which we propose will extend the therapeutic horizon and provide a new form of remote-controlled healing.
The remote dynamic MNP tagging of cells is a novel methodology with multiple applications across a wide area of healthcare and biomedical research. The impact will be far reaching with the development of a disruptive technology platform in healthcare. We have patented our platform applications and spun out a company, MICA Biosystems Ltd. which will be progressing this forward at the completion of the project towards commercialisation. We are generating impact through our Dynamic Drug Screening platform, DYNASCREEN, which has been funded by the UK Government Innovate Scheme.
Our exciting innovation will be to progress our magnetic tagged approach to first in man using our clinic ready technology. We have applied for an ERC POC which will enable us to take the platform to the clinic for spinal fusion.
At the end of the project, we have obtained data which we use for reaching out to regulatory bodies to obtain approvals for a first in man trial.
Finally, we have established significant research avenues to explore in progressing our basic understanding of the role of mechanoreceptors on the cell membrane.
Our exciting innovation will be to progress our magnetic tagged approach to first in man using our clinic ready technology. We have applied for an ERC POC which will enable us to take the platform to the clinic for spinal fusion.
At the end of the project, we have obtained data which we use for reaching out to regulatory bodies to obtain approvals for a first in man trial.
Finally, we have established significant research avenues to explore in progressing our basic understanding of the role of mechanoreceptors on the cell membrane.