LUMINESCENT IMPLANTS AS PORTS FOR LIGHT-BASED THERAPIES

Introduction

A major difficulty in developing clinically useful treatments is to deliver therapeutic action with spatiotemporal precision and pharmacological specificity. This unmet need is exemplified in two conditions:

1. Neuropathic Pain: This condition is due to abnormal inflammation and/or excitability of localized somatosensory nerves, sometimes resembling sudden stabbings or electric shocks.
2. Epilepsy: A disease characterized by seizures that are due to a transient state of synchronized firing of a localized population of cortical neurons.

Current Treatment Limitations

Inflammation can be treated with photobiomodulation (PBM) but requires localized delivery of light. These conditions can also be treated with neuroinhibitory drugs, such as:

• Inhibitors of sodium channels
• Potentiators of GABAa receptors

However, the systemic adverse side effects of these drugs pose limitations to their safety and efficacy. Additionally, once administered, their activity cannot be controlled.

Proposed Solution

To address this issue, we will use locally emitted light, which delivers anti-inflammatory action by PBM. This approach allows for the on and off control of the pharmacological action of photoswitchable drugs locally and on demand.

Development of PhotoTheraPorts

To illuminate the target sites in the body, we will develop PhotoTheraPorts, which are light-emitting implants based on upconverting nanoparticles. Key features include:

• Controlled Emission: Their visible light emission can be controlled remotely and noninvasively with infrared light applied externally through the tissue and bone.
• High Efficacy: Their encapsulation offers high efficacy and long-term tolerability.

Drug Development and Testing

We will also develop suitable photoswitchable drugs with anti-inflammatory and neuroinhibitory activity. The plan includes:

1. Preclinical testing of the efficacy and safety of both devices and drugs.
2. Demonstrating a novel treatment modality to reduce inflammation and neuroinhibition locally and on demand.

Expected Impact

We aim to conduct preclinical studies in well-established animal models of:

• Inflammatory and neuropathic pain (peripheral, spinal cord, brain cingulate cortex)
• Epilepsy (focal seizures)

This research is expected to produce a deep impact in the management of these conditions.