Precursor-Engineering Hierarchical Architecture Nanozymes Loading with Cisplatin for Redox Homeostasis Modulation in...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Immunotherapy and chemotherapy are key cancer treatments but face challenges like immunosuppressive tumor microenvironments, systemic toxicity, and drug resistance.
• Current strategies require improvement for effective drug delivery and targeting to overcome these limitations.

Purpose of the Study:

• To design multifunctional nanozymes for enhanced cancer treatment by addressing immunotherapy and chemotherapy limitations.
• To develop a targeted drug delivery system that reverses the immunosuppressive tumor microenvironment and improves therapeutic efficacy.

Main Methods:

• Engineered multifunctional nanozymes using cerium oxide templates and zirconium precursor for hierarchical porous structures via the Kirkendall effect.
• Loaded nanozymes with cisplatin, utilizing hyaluronic acid for high-capacity loading and tumor-specific targeting.
• Investigated ultrasound-amplified redox homeostasis modulation and its synergy with cisplatin-induced DNA damage.

Main Results:

• Hierarchical porous nanozymes exhibited enhanced triple enzymatic activity and facilitated efficient mass transfer.
• Hyaluronic acid conjugation enabled high-capacity cisplatin loading and specific tumor targeting, reducing off-target effects.
• Nanozymes modulated redox homeostasis, synergized with cisplatin to induce oxidative stress and DNA damage, reversing immunosuppressive tumor microenvironments and promoting cancer cell death.

Conclusions:

• The developed nanozyme system effectively overcomes limitations of traditional cancer immunotherapies and chemotherapies.
• This approach shows promise for concurrent tumor cell death and immunogenic cell death, offering a new strategy for malignancy treatment.
• The study highlights the potential of nanozymes in combination cancer therapy by improving drug delivery and modulating the tumor microenvironment.