Activatable Cancer Sono-Immunotherapy using Semiconducting Polymer Nanobodies

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunotherapy

Background:

• Sonodynamic therapy (SDT) shows promise for cancer treatment but faces challenges with uncontrolled drug activity and inefficient sonosensitizers.
• Current SDT lacks precise spatiotemporal control, limiting its clinical translation in combination cancer therapies.

Purpose of the Study:

• To develop efficient semiconducting polymer sonosensitizers for activatable cancer immunotherapy.
• To engineer sono-immunotherapeutic nanobodies (SPN_Ab) for precise spatiotemporal control of cancer treatment.

Main Methods:

• Conjugation of anti-CTLA-4 antibodies onto polymer nanoparticles via a singlet oxygen-cleavable linker to create SPN_Ab.
• Utilizing ultrasound irradiation to activate SPN_Ab, generating singlet oxygen (¹O₂) and releasing antibodies in situ.
• Evaluating the synergistic effects of SDT and immunotherapy on T-cell responses and tumor progression in vivo.

Main Results:

• SPN_Ab generated ¹O₂ upon sono-irradiation, inducing immunogenic cell death and releasing anti-CTLA-4 antibodies.
• The combined sonodynamic and immunotherapy approach effectively promoted cytotoxic T lymphocyte proliferation and depleted regulatory T cells.
• Demonstrated significant tumor regression, inhibition of metastasis, and establishment of durable immunological memory, preventing relapse.

Conclusions:

• Developed a novel semiconducting polymer-based nanobody system for activatable sono-immunotherapy.
• Achieved precise spatiotemporal control over therapeutic agent release and immune response modulation.
• This strategy offers a promising proof-of-concept for advanced cancer treatment by combining SDT with targeted immunotherapy.