Biodegradable and Piezoelectric Mn-Doped Hydroxyapatite for Sonodynamic Immunotherapy

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Tumor microenvironments are typically immunosuppressive, hindering effective cancer treatment.
• Pyroptosis, a form of programmed cell death, can stimulate antitumor immune responses.
• Existing metal-ion strategies for pyroptosis induction are limited by intracellular ion buffering systems.

Purpose of the Study:

• To develop a biodegradable manganese-doped hydroxyapatite (Mn-HAP) material as a sonoimmune stimulator.
• To investigate the ultrasound-triggered continuous reactive oxygen species (ROS) modulation for enhanced antitumor effects.
• To explore the potential of Mn-HAP in overcoming ion buffering limitations and promoting pyroptosis-induced immunotherapy.

Main Methods:

• Synthesis of biodegradable manganese-doped hydroxyapatite (Mn-HAP) nanoparticles.
• Utilizing ultrasound (US) to trigger reactive oxygen species (ROS) generation and modulate the tumor microenvironment.
• Investigating the role of Mn-HAP degradation, Ca2+ influx, and Mn2+ release in activating cellular pathways.
• Evaluating the combined effects of sonodynamic therapy and pyroptosis induction on innate immunity and immunotherapy.

Main Results:

• Mn-HAP demonstrated enhanced sonodynamic antitumor effects due to Mn-doping and oxygen vacancies.
• Ultrasound activation induced Ca2+ influx via cell membrane ion channels.
• Degradation of Mn-HAP released Ca2+ and ROS, promoting pyroptosis.
• Released Mn2+ activated the cGAS-STING pathway, enhancing innate immunity and pyroptosis-induced immunotherapy.

Conclusions:

• Biodegradable Mn-HAP acts as a sonoimmune stimulator, combining sonosensitizer and immune agent functions.
• The developed material effectively overcomes ion buffering issues to induce pyroptosis.
• This strategy provides a promising approach for engineering materials for sonodynamic immunotherapy of solid tumors.