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Published on: December 1, 2016
Sprayable paclitaxel/cerium oxide nanozyme-integrated PLGA nanocarrier suppresses nasopharyngeal carcinoma via ROS
1Otolaryngology & Head and Neck Center, Cancer Center, Department of Otolaryngology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Abstract:
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.
Insights
This study developed a sprayable nanocarrier combining chemotherapy with nanozyme activity for nasopharyngeal carcinoma (NPC) treatment. The novel therapy effectively inhibited tumor growth and reduced recurrence risk with minimal systemic toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Nasopharyngeal carcinoma (NPC) presents challenges in treatment due to recurrence, inflammation-driven progression, and chemotherapy toxicity.
- Current therapies often lack localized efficacy and can cause significant systemic side effects.
Purpose of the Study:
- To develop a novel sprayable nanocarrier system for localized NPC therapy.
- To synergistically combine chemotherapy with nanozyme activity for enhanced treatment efficacy.
- To investigate the therapeutic potential of paclitaxel/cerium oxide nanozyme-integrated poly(lactic-co-glycolic acid) nanocarriers (PTX/CeO₂-PLGA NC) for NPC.
Main Methods:
- Fabrication and characterization of PTX/CeO₂-PLGA NC with controlled size, charge, and drug encapsulation.
- In vitro assessment of nanocarrier cytotoxicity, ROS modulation, mitochondrial function, and apoptosis induction in NPC cells.
- In vivo evaluation of therapeutic efficacy and systemic toxicity in an immunocompetent NPC model via intranasal administration.
- Analysis of mechanistic pathways including NF-κB and STAT3 signaling.
Main Results:
- Optimized PTX/CeO₂-PLGA NC exhibited favorable physicochemical properties and sustained drug release.
- The nanocarriers demonstrated superior in vitro inhibition of NPC cell viability compared to paclitaxel alone.
- In vivo studies showed significant tumor growth inhibition (71.4%) with reduced systemic toxicity compared to free paclitaxel.
- The therapy effectively modulated intracellular ROS, restored antioxidant activity, induced apoptosis, and inhibited NF-κB/STAT3 signaling.
Conclusions:
- Sprayable PTX/CeO₂-PLGA NC offers a promising localized therapeutic strategy for NPC.
- The combination of chemotherapy and nanozyme activity provides synergistic effects by scavenging ROS and inhibiting key oncogenic pathways.
- This approach presents a safe and effective alternative to conventional chemotherapy for NPC treatment.
