Sprayable paclitaxel/cerium oxide nanozyme-integrated PLGA nanocarrier suppresses nasopharyngeal carcinoma via ROS scavenging and NF-κB/STAT3 inhibition.

Nasopharyngeal carcinoma (NPC) remains difficult to treat due to high local recurrence, inflammation-driven tumor progression, and the systemic toxicity of conventional chemotherapy. Herein, this study developed a sprayable paclitaxel/cerium oxide nanozyme-integrated poly(lactic-co-glycolic acid) nanocarrier (PTX/CeO₂-PLGA NC) for localized NPC therapy by synergistically combining chemotherapy with reactive oxygen species (ROS)-modulating nanozyme activity. The optimized nanocarriers had a uniform nanoscale size (164.9 ± 9.2 nm), a small size distribution (PDI 0.21 ± 0.03), and a stable negative surface charge (-22.7 ± 1.9 mV). PTX was effectively encapsulated with an encapsulation efficiency of 82.6 ± 3.4% and a drug loading of 8.1 ± 0.6%, which showed sustained release with minimal burst release. In vitro experiments showed that PTX@CeO₂-PLGA NC effectively inhibited the viability of CNE-1 and CNE-2 NPC cells to approximately 25% at 24 h, whereas only about 52% inhibition was achieved for PTX, while keeping over 80% viability of normal NP69 cells. The nanozyme-integrated system reduced intracellular ROS levels by approximately 60%, restored antioxidant enzyme activity, disrupted mitochondrial membrane potential, and increased apoptotic cell populations to ∼69%. In vivo intranasal administration in an immunocompetent NPC model resulted in pronounced tumor growth inhibition (71.4%), significantly outperforming PTX (43.5%), without observable systemic toxicity. Mechanistically, the expression of tumor NF-κB p65 and STAT3 was significantly inhibited to ∼0.3-fold of the control level. Hence, the current findings clearly indicate that sprayable PTX@CeO₂-PLGA NC are a safe and effective local therapeutic approach for NPC by combining chemotherapy with ROS scavenging and inhibition of the NF-κB/STAT3 pathway.