Boosting Sonodynamic/Gas/Chemo Therapy through Triple Inhibiting Multidrug Resistance Using Responsive Biodegradable...

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Triple-negative breast cancer (TNBC) treatment relies on non-targeted chemotherapy, leading to multidrug resistance and severe side effects.
• Developing novel therapeutic strategies is crucial to overcome current limitations in TNBC treatment.

Purpose of the Study:

• To develop a responsive, biodegradable zinc-doped MoS_2-x nanosheet (ZMS) platform for enhanced sono-chemotherapy in TNBC.
• To investigate the ZMS platform's ability to inhibit multidrug resistance via triple-pathway modulation (ROS, H₂S, Zn²⁺).

Main Methods:

• Fabrication of zinc-doped MoS_2-x nanosheets (ZMS) with rich sulfide vacancies.
• Utilizing ultrasound (US) activation to enhance reactive oxygen species (ROS) generation for sonodynamic therapy (SDT).
• Investigating the degradation of ZMS/DOX in the acidic tumor microenvironment (TME) to release DOX, Zn²⁺, and H₂S.

Main Results:

• Zn doping in MoS_2-x inhibited electron-hole recombination, boosting ROS generation for enhanced SDT.
• Released Zn²⁺ and H₂S synergistically reduced intracellular ATP levels, disrupting glycolysis and mitochondrial function.
• Reduced ATP levels suppressed P-glycoprotein expression, overcoming drug resistance.
• ZMS exhibited catalase-like activity, converting H₂O₂ to O₂, alleviating tumor hypoxia and enhancing therapeutic efficacy.

Conclusions:

• The developed biodegradable ZMS platform effectively enhances sono-chemotherapy for TNBC.
• This approach simultaneously inhibits multidrug resistance and reduces chemotherapy side effects.
• The ZMS platform shows significant promise for improving TNBC treatment outcomes.