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 key 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: This disease is 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 (e.g., inhibitors of sodium channels, potentiators of GABAa receptors). However, their systemic adverse side effects pose limitations to their safety and efficacy. Additionally, once administered, their activity cannot be controlled.

Proposed Solution

To address these issues, we will use locally emitted light, which delivers anti-inflammatory action by PBM. This approach also 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, light-emitting implants based on upconverting nanoparticles. Their visible light emission can be controlled remotely and noninvasively with infrared light applied externally through the tissue and bone. Key features include:

• High efficacy
• Long-term tolerability

Drug Development

We will also develop suitable photoswitchable drugs with anti-inflammatory and neuroinhibitory activity.

Preclinical Testing

We will preclinically test the efficacy and safety of both devices and drugs. Our goal is to demonstrate a novel treatment modality to reduce inflammation and neuroinhibition locally and on demand in well-established animal models of:

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

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