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<p>Oral squamous cell carcinoma (OSCC) is known to inadequate therapies outcomes due to low efficacy and inflammatory toxicity of conventional chemotherapy. Herein, this study was developed cisplatin-loaded cerium oxide nanozymes (Cis@CeO₂ NZs) as a multi-functional platform to improve the anticancer properties by modulating redox and regulating anti-inflammatory responses. Cerium oxide nanozymes were successfully synthesized using controlled precipitation method and it showed high efficiency in Cis loading (encapsulation efficiency ~ 68–75%, drug loading ~ 12–18%) with sustained release of the drug (~ 75–80% in 48&#xa0;h). In vitro studies conducted on SCC-9 and CAL-27 cells revealed a significant improvement in the cytotoxic potential of Cis@CeO₂ NZs compared to Cis, with a ~ 1.8-2.0-fold decrease in IC₅₀ values. Cis@CeO₂ NZs caused substantial oxidative stress, as indicated by a 3.5-4.0-fold increase in intracellular ROS and a ~ 60–70% reduction in antioxidant enzymes (SOD, CAT, GSH). These changes led to substantial mitochondrial membrane potential depolarization (JC-1 red/green ratio decreased to ~ 0.31) and increased apoptosis, with ~ 65–75% apoptotic/necrotic cells observed by AO-EB staining and ~ 70% apoptotic nuclei detected by DAPI staining. Moreover, Cis@CeO₂ NZs caused significant inhibition of cancer cell migration, with a ~ 17–19% wound closure area compared to ~ 75–80% in control cells. Notably, Cis@CeO₂ NZs attenuated Cis induced inflammation and downregulating TNF-α, IL-6, and NF-κB expression by ~ 70–80% at the transcriptional level. Hence, these findings shed light on Cis@CeO₂ NZs delivery as a potent, mechanism-driven strategy for improving OSCC chemotherapy.</p>

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Redox-responsive cisplatin-loaded cerium oxide nanozymes for oral squamous cell carcinoma: oxidative stress modulation, anti-inflammatory activity, and enhanced cytotoxicity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月19日

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  • Xuesong Zhai,
  • Xuesong Wu,
  • Lizhen Ren,
  • Dongguang Qin,
  • Wei Ding

摘要

Oral squamous cell carcinoma (OSCC) is known to inadequate therapies outcomes due to low efficacy and inflammatory toxicity of conventional chemotherapy. Herein, this study was developed cisplatin-loaded cerium oxide nanozymes (Cis@CeO₂ NZs) as a multi-functional platform to improve the anticancer properties by modulating redox and regulating anti-inflammatory responses. Cerium oxide nanozymes were successfully synthesized using controlled precipitation method and it showed high efficiency in Cis loading (encapsulation efficiency ~ 68–75%, drug loading ~ 12–18%) with sustained release of the drug (~ 75–80% in 48 h). In vitro studies conducted on SCC-9 and CAL-27 cells revealed a significant improvement in the cytotoxic potential of Cis@CeO₂ NZs compared to Cis, with a ~ 1.8-2.0-fold decrease in IC₅₀ values. Cis@CeO₂ NZs caused substantial oxidative stress, as indicated by a 3.5-4.0-fold increase in intracellular ROS and a ~ 60–70% reduction in antioxidant enzymes (SOD, CAT, GSH). These changes led to substantial mitochondrial membrane potential depolarization (JC-1 red/green ratio decreased to ~ 0.31) and increased apoptosis, with ~ 65–75% apoptotic/necrotic cells observed by AO-EB staining and ~ 70% apoptotic nuclei detected by DAPI staining. Moreover, Cis@CeO₂ NZs caused significant inhibition of cancer cell migration, with a ~ 17–19% wound closure area compared to ~ 75–80% in control cells. Notably, Cis@CeO₂ NZs attenuated Cis induced inflammation and downregulating TNF-α, IL-6, and NF-κB expression by ~ 70–80% at the transcriptional level. Hence, these findings shed light on Cis@CeO₂ NZs delivery as a potent, mechanism-driven strategy for improving OSCC chemotherapy.