CAREER: Molecular Design Rules for Self-Reporting Biophotonic Nanoprobes to Elucidate Intracellular Pathways Driving Chronic Pain

Chronic pain affects millions of Americans and remains difficult to treat without relying on opioid drugs. To develop more effective pain treatments, scientists need better tools to study pain signals in nerve cells. Recent research suggests that pain signaling occurs at receptors on the surface of neurons and can continue from inside the cell after surface receptors are internalized. Existing tools cannot directly study these internal processes. This CAREER project will develop tiny, light-responsive particles that can enter nerve cells and turn off pain-signaling receptors when illuminated with light. These particles will also emit light, allowing researchers to see where pain signals have been disrupted inside cells. This work will provide new insight into pain biology and may help identify targets for non-opioid pain therapies. The research is integrated with a strong education and outreach program designed to inspire the next generation science and engineering workforce. Overall, this project serves the national interest through biotechnology innovation, workforce development, and progress toward safe and effective health solutions. This CAREER project will develop innovative light-responsive particles to study intracellular pain signaling in sensory neurons. New light-responsive chemistries will be developed that can release bioactive molecules and generate a fluorescent reporter upon illumination. These light-responsive molecules will be combined with internal fluorescent quantum dot standards and incorporated into nanoparticles to create self-reporting probes that function inside living cells. By studying how molecular structure and nanoscale environment affect probe properties, the project will establish rules for designing efficient, self-reporting, light-activated nanoparticles. Beyond pain research, these probes will be broadly applicable tools for cell biology and biomedical research. The probes could be leveraged to identify novel therapeutic targets. In the long term, this work will enable deeper insight into chronic pain mechanisms and accelerate the development of non-opioid therapies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.