STING-Activating nanoplatforms for image-guided sonodynamic cancer therapy

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Precision cancer treatment requires real-time monitoring, a current challenge.
• Nanomedicine offers integrated nano-platforms for enhanced tumor diagnosis and treatment.
• Ultrasound (US) activated therapies show promise for targeted cancer treatment.

Purpose of the Study:

• To develop a multimodal diagnostic nanodrug for immuno-sonodynamic therapy targeting breast cancer.
• To integrate sonosensitizers, STING agonists, and radionuclides for combined diagnosis and therapy.
• To enable real-time monitoring and precise therapeutic intervention in breast cancer models.

Main Methods:

• Created a nanodrug (⁹⁹ᵐTc-NPᴬᴵᴱ-MSA) with aggregation-induced luminescence properties.
• Utilized US activation to generate reactive oxygen species and trigger the cGAS-STING pathway.
• Incorporated ⁹⁹ᵐTc for SPECT/CT and fluorescence imaging, and released STING agonist MSA-2.
• Evaluated anti-tumor effects and immunomodulation in vitro and in vivo.

Main Results:

• US activation generated reactive oxygen species, causing DNA and mitochondrial damage.
• The nano-platform successfully activated the cGAS-STING pathway and released MSA-2.
• ⁹⁹ᵐTc facilitated precise tumor targeting and monitoring via imaging modalities.
• Significant anti-tumor effects and immunomodulation were observed in vitro and in vivo.

Conclusions:

• The developed nanodrug ⁹⁹ᵐTc-NPᴬᴵᴱ-MSA is effective for immuno-sonodynamic therapy in breast cancer.
• This multimodal platform offers precise tumor diagnosis, monitoring, and treatment capabilities.
• The strategy presents a novel approach for advanced, image-guided cancer therapy and immunomodulation.