(36a) Engineering and Manufacturing Nanoparticles to Study and Treat Oral Cancer Pain

Cancer pain is a complex and often debilitating cancer symptom driven by diverse mechanisms associated with tumor progression and therapeutic intervention. These tumor- and treatment-induced factors contribute to the multifaceted and frequently treatment-resistant nature of cancer pain, underscoring the urgent need for innovative therapeutic strategies. Oral cancers, which affect approximately 30,000 Americans annually, exemplify this challenge. Not only are these cancers difficult to treat, but they also produce persistent and severe pain. Current therapeutic options remain limited, with opioid analgesics serving as the standard of care—despite their well-documented drawbacks, including sedation, respiratory depression, constipation, tolerance, and dependence.

To address these unmet needs in cancer and chronic pain, in the Pinkerton Group, we design highly engineering polymeric nanoparticles using novel scalable manufacturing methods. Our research integrates tools from chemistry, nanotechnology, and chemical engineering to design nanomaterials that interact selectively with the tumor microenvironment, including immune cells and sensory neurons. We aim to uncover structure–property relationships that guide the rational design of nanoparticles for specific biological interactions. Our systems are engineered for precision through (1) spatiotemporal control of drug release enabled by two-photon near-infrared (NIR) light responsiveness, (2) tailored physicochemical properties to optimize cellular uptake and intracellular trafficking, and (3) versatility in delivering diverse therapeutic cargos, ranging from small molecules to biologics. In this presentation, I will highlight our recent advances in these areas, with a focus on modular nanoparticle assembly strategies, including flash nanoprecipitation and sequential nanoprecipitation. I will also discuss our efforts to develop nanoparticle-based therapeutics for treating oral cancer pain and emerging nanoparticle platforms for probing pain signaling pathways.