Selective Nanoblocker of Cellular Stress Response for Improved Drug-Free Tumor Therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Nanotechnology offers drug-free therapeutic strategies, but cellular stress responses (CSR) impede efficacy.
• External stimuli activate CSR, significantly reducing the effectiveness of drug-free antitumor treatments.

Purpose of the Study:

• To develop a novel drug-free nanoagent that regulates CSR for enhanced antitumor therapy.
• To investigate the efficacy of glucose oxidase-modified Cu3BiS3 nanosheets encapsulated by calcium carbonate (CBSG@CaCO3) in overcoming CSR.

Main Methods:

• Synthesis of glucose oxidase (GOx)-modified Cu3BiS3 nanosheets (CBSG NSs) encapsulated by calcium carbonate (CBSG@CaCO3).
• Utilizing NIR-II photothermal properties and CaCO3 shell for controlled release and CSR inhibition.
• Investigating the mechanism of CSR regulation by inhibiting P27 and NRF2 expression.

Main Results:

• CBSG@CaCO3 nanoagent effectively generates external stimuli and disrupts CSR mechanisms.
• The nanoagent demonstrates selective treatment of tumor cells by exploiting differences in physiological conditions.
• Inhibition of P27 and NRF2 expression by CaCO3 disrupts cancer cell adaptive viability.

Conclusions:

• The developed CSR regulation strategy significantly improves the efficacy of drug-free starvation-chemodynamic therapy (ST-CDT).
• This approach offers a promising new avenue for cancer treatment by overcoming CSR-induced limitations.
• The selective targeting of tumor cells enhances therapeutic outcomes and minimizes damage to normal cells.