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Updated: Jun 1, 2025
Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria
Published on: May 16, 2025
GSH/pH-responsive copper-based cascade nanocomplexes inducing immunogenic cell death through
Yi Sun1, Enze Li2, Wenzhao Zhong2
1Stomatology Department, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China.
Abstract:
Oral squamous cell carcinoma (OSCC) remains a formidable challenge due to high recurrence rates and limited efficacy of conventional treatments. Immunotherapy holds potential, but its effectiveness is often restricted by low patient responsiveness. This study presents a novel therapeutic strategy using GSH/pH-responsive copper-based cascade nanocomplexes to induce immunogenic cell death (ICD) in OSCC. The fabricated nanocomplex, PC@B-H, leverages the acidic and reducing tumor microenvironment to release copper ions and plumbagin, triggering a cascade of cell death mechanisms including cuproptosis, ferroptosis, and necroptosis. This multifunctional system not only enhances oxidative stress but also depletes glutathione, promotes lipid peroxidation, and disrupts mitochondrial function, leading to robust tumor inhibition. Additionally, the induction of ICD facilitates dendritic cell maturation and cytotoxic T lymphocyte infiltration, providing durable anti-tumor immunity. The study demonstrates that PC@B-H achieves a 92.3 % tumor growth inhibition rate with minimal systemic toxicity, offering a promising avenue for enhancing the efficacy of OSCC treatment through combined cell death pathways and immune activation.
Insights
This study introduces a novel nanocomplex for oral cancer, triggering multiple cell death pathways and enhancing immune response. This approach shows significant tumor inhibition with low toxicity, offering a promising new treatment strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to high recurrence and limited therapeutic options.
- Immunotherapy shows promise for OSCC but is hampered by low patient response rates.
Purpose of the Study:
- To develop a novel GSH/pH-responsive copper-based cascade nanocomplex (PC@B-H) for inducing immunogenic cell death (ICD) in OSCC.
- To investigate the combined effects of cuproptosis, ferroptosis, and necroptosis for enhanced anti-tumor activity.
Main Methods:
- Fabrication of PC@B-H nanocomplexes designed to respond to the tumor microenvironment (acidic and reducing conditions).
- Evaluation of the nanocomplex's ability to release copper ions and plumbagin, inducing multiple cell death pathways.
- Assessment of the impact on oxidative stress, glutathione levels, lipid peroxidation, and mitochondrial function.
- Analysis of ICD induction, dendritic cell maturation, and cytotoxic T lymphocyte infiltration.
Main Results:
- The PC@B-H nanocomplex effectively triggered a cascade of cell death mechanisms, including cuproptosis, ferroptosis, and necroptosis.
- The system enhanced oxidative stress, depleted glutathione, promoted lipid peroxidation, and disrupted mitochondrial function.
- PC@B-H demonstrated a 92.3% tumor growth inhibition rate with minimal systemic toxicity.
- Induction of ICD led to increased dendritic cell maturation and cytotoxic T lymphocyte infiltration, suggesting durable anti-tumor immunity.
Conclusions:
- The developed GSH/pH-responsive copper-based cascade nanocomplex (PC@B-H) offers a potent strategy for OSCC treatment.
- Combining multiple cell death pathways and immune activation via ICD presents a promising therapeutic avenue for OSCC.
- This novel approach holds potential for improving treatment efficacy and overcoming resistance in oral cancer therapy.
