A Surface-Engineered Cerium Oxide Nanozyme Functionalized with L-Theanine for Redox and Inflammatory Modulation in Neuropathic Pain

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Background: Neuropathic pain is associated with interacting oxidative stress-, neuroinflammation-, and apoptosis-related processes, whereas current therapies mainly provide symptomatic relief without fully addressing these pathological components. To overcome this limitation, we developed a surface-engineered nanozyme platform composed of poly(acrylic acid)-coated cerium oxide nanoparticles functionalized with L-theanine (CPT), aiming to combine the redox activity of nanoceria with the bioactivity of a neuroprotective small molecule. Results: Physicochemical characterization demonstrated that L-theanine functionalization did not alter the crystalline structure or mixed Ce 3 ⁺/Ce 4 ⁺ valence state of nanoceria. In H 2 O 2 -challenged Schwann cells, CPT significantly reduced intracellular reactive oxygen species, improved cell viability, and suppressed the expression of inflammation- and apoptosis-related genes more effectively than free L-theanine or nanoparticle controls. In a rat chronic constriction injury model, repeated administration of CPT improved mechanical and thermal hypersensitivity. These behavioral improvements were accompanied by reduced spinal oxidative and nitrosative stress, partial restoration of endogenous antioxidant defenses, suppression of pro-inflammatory cytokines, and decreased caspase-3 activity. Conclusion: These findings suggest that CPT attenuates oxidative stress-, inflammatory cytokine-, and caspase-3-associated responses in both H 2 O 2 -challenged Schwann cells and a rat CCI model of neuropathic pain. Rather than establishing a complete mechanistic pathway, the present study provides preliminary evidence that surface-functionalized nanoceria may serve as a nanozyme-based candidate for redox- and inflammation-associated modulation in neuropathic pain. Keywords: neuropathic pain, cerium oxide nanozyme, L-theanine, oxidative stress, neuroinflammation, chronic constriction injury

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