Developing immunotherapeutic nanoparticles for spinal cord injury

Traumatic spinal cord injury (SCI) leads to primary injury, followed by secondary injuries including inflammation which create an inhibitory environment.

Regeneration is limited due to additional tissue damages and an inhibitory environment, leading to various neurological deficits.

The goal of this proposal is to develop a non-invasive acute intervention with the goal of modulating inflammatory responses to reprogram an inhibitory environment after SCI.

Particularly, the SCI demographic shifts toward a more equal balance among males and females, indicating that improved therapeutics are needed since the difference in physiological factors between sexes play important roles in pharmacological treatments and functional recovery after SCI.

In this study, Poly(lactide-co-glycolide) (PLG)-based multiple nanoparticle (NP) formulations will be designed with various physicochemical factors to identity sex-specific key functionality of NPs to reprogram inflammation, thereby facilitating functional recovery in females and males respectively after SCI.

Specific aim 1 will investigate NP-induced innate cells modulation following SCI to identify sex-specific key properties of NPs. The distinct physicochemical properties of NPs will differently limit inflammation after SCI.

Specific aim 2 will assess NPs-mediated long-term dynamic responses in the spinal cord and their effects on anatomical and functional recovery in both sexes after SCI.

Intravenously (IV) administered NPs will bind to pro-inflammatory subsets of immune populations and direct their trafficking to the spleen.

NP-positive innate cells within the injured tissues will lead to a sustained response, facilitating an environment that improves recovery after SCI.

Successful completion of proposed aims will provide efficient sex-specific NP designs to maximize functional recovery after SCI.

In addition, NPs are made of FDA-approved material that enables NPs to be administered in triage or on site to patients diagnosed with SCI without direct intervention into the spinal cord. This study will provide a potentially practical therapy for the entire SCI population.