Precision cancer sono-immunotherapy using deep-tissue activatable semiconducting polymer immunomodulatory...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Nanomedicine offers potential for cancer immunotherapy but struggles with specificity and immune tolerance.
• Developing targeted therapies that elicit anti-tumor immunity without adverse effects remains a challenge.

Purpose of the Study:

• To develop a deep-tissue activatable cancer sono-immunotherapy platform.
• To create novel semiconducting polymer nanoparticles (SPINs) for targeted drug delivery and immune activation.

Main Methods:

• Synthesized a semiconducting polymer generating high levels of sonodynamic singlet oxygen (¹O₂).
• Conjugated immunomodulators to the polymer via ¹O₂-cleavable linkers to form SPINs.
• Evaluated SPINs' efficacy in preclinical pancreatic and rabbit tumor models under ultrasound irradiation.

Main Results:

• SPINs demonstrated superior singlet oxygen generation compared to existing sonosensitizers.
• Ultrasound-activated SPINs effectively debulked tumors, reprogrammed the tumor microenvironment, and enhanced immunogenicity.
• Targeted release of immunomodulators at the tumor site led to tumor elimination and prevention of relapse in mouse models.
• SPINs showed significant antitumor efficacy in a rabbit tumor model with reduced immune-related adverse events.

Conclusions:

• The developed SPINs represent a promising precision sono-immunotherapy approach for deep-tissue tumors.
• This strategy effectively harnesses sonodynamic activation for targeted anti-tumor immunity with improved safety profile.
• SPINs hold potential for treating various cancers, including pancreatic cancer, with reduced systemic toxicity.