Ultrasound-Responsive Cerasome Nanoparticle Improves STING-Driven Immunotherapy in Triple-Negative Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunotherapy

Background:

• Triple-negative breast cancer (TNBC) immunotherapy faces challenges including low response rates and poor immune cell infiltration.
• Existing treatments often lead to systemic side effects and lack targeted delivery mechanisms.

Purpose of the Study:

• To develop an ultrasound-responsive cerasomal nanoplatform for synergistic sonodynamic-immunotherapy in TNBC.
• To enhance localized immune activation and improve therapeutic efficacy by integrating a STING agonist (SR-717).

Main Methods:

• Self-assembly of nanoparticles using cerasome-forming lipids, porphyrin-conjugated lipids, phospholipids, and iRGD.
• Loading of STING agonist SR-717 into the lipid bilayer of the nanoparticles.
• Ultrasound irradiation to trigger reactive oxygen species (ROS) generation and on-demand drug release for localized STING pathway activation.

Main Results:

• The developed nanoparticles demonstrated high SR-717 loading, exceptional stability, and tumor-specific accumulation via iRGD.
• Ultrasound-triggered ROS generation led to cerasome disruption and on-demand SR-717 release.
• Activated STING pathway promoted type-I interferon production, dendritic cell maturation, and significant CD8+ T-cell infiltration.

Conclusions:

• The cerasomal nanoplatform effectively integrates sonodynamic therapy with localized immune activation for TNBC.
• This approach overcomes limitations of instability and inefficient delivery, offering a precise strategy to stimulate antitumor immunity.
• The developed platform shows promise for enhancing therapeutic outcomes in TNBC, a cancer with limited targeted therapy options.