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An Innovative Strategy for the Redox Balance in Breast Cancer with Wool Keratin-Stabilized Copper Nanozyme
Qikuan He1, Hongji Wu2, Meilin Guo2
1Department of General Surgery, The Affiliated Lihuili Hospital of Ningbo University, Ningbo315046, China.
Abstract:
Breast cancer, particularly the triple-negative subtype, poses a significant clinical challenge due to its aggressive behavior and lack of effective therapeutic targets. Current treatments are generally limited by drug resistance and systemic toxicity. This study developed a WK peptide-guided copper-based nanozyme that targets the redox balance in tumor lesions. Functionally, this nanozyme exhibits peroxidase-like activity, converting endogenous hydrogen peroxide into cytotoxic radicals while depleting glutathione, thereby disrupting redox homeostasis through a dual mechanism. Mechanistically, in vitro and in vivo experiments demonstrate that the nanozyme effectively induces a ROS burst in breast cancer cells, inhibits the PI3K-AKT-mTOR signaling pathway, and triggers apoptosis, leading to significant tumor suppression. In summary, this work translates nanozyme technology into a promising therapeutic strategy with the potential to overcome treatment resistance in breast cancer.
Insights
This study introduces a novel nanozyme therapy for triple-negative breast cancer. This copper-based nanozyme effectively targets tumor redox balance, inducing cancer cell death and suppressing tumor growth.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic options.
- Existing treatments for TNBC often face limitations such as drug resistance and systemic toxicity.
- Targeting tumor-specific redox imbalances offers a potential strategy to overcome these challenges.
Purpose of the Study:
- To develop and evaluate a novel nanozyme for targeting redox balance in breast cancer.
- To investigate the therapeutic efficacy of a WK peptide-guided copper-based nanozyme in TNBC models.
- To explore the mechanisms underlying nanozyme-induced cancer cell death and tumor suppression.
Main Methods:
- Development of a WK peptide-guided copper-based nanozyme with peroxidase-like activity.
- In vitro assays to assess nanozyme's effect on reactive oxygen species (ROS) generation and glutathione depletion in cancer cells.
- In vivo studies in tumor-bearing models to evaluate tumor suppression and apoptosis induction.
- Analysis of the PI3K-AKT-mTOR signaling pathway modulation.
Main Results:
- The nanozyme demonstrated significant peroxidase-like activity, generating cytotoxic radicals and depleting glutathione.
- Nanozyme treatment led to a substantial ROS burst in breast cancer cells, disrupting redox homeostasis.
- Inhibition of the PI3K-AKT-mTOR signaling pathway and induction of apoptosis were observed.
- Significant tumor suppression was achieved in vivo, indicating therapeutic potential.
Conclusions:
- The developed nanozyme represents a promising therapeutic strategy for overcoming treatment resistance in breast cancer.
- Targeting redox balance via nanozyme technology offers a novel approach for TNBC treatment.
- Further research into nanozyme-based therapies could lead to improved clinical outcomes for breast cancer patients.
