Tumor/Lymph Node Dual-Targeting Ultrasonic Nanoconverter Orchestrates Spatiotemporal ROS Regulation for Dual-Zone...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Tumor-draining lymph node (tdLN) metastasis is a major challenge in breast cancer treatment.
• Current therapies struggle with effective delivery to both primary tumors and tdLNs, limiting efficacy.
• Inhibition of tumor invasion and metastasis is crucial for improving patient outcomes.

Purpose of the Study:

• To develop a dual-targeting nanoconverter (OPD@PSF) for co-delivering a sonosensitizer (PpIX) and a STING agonist (DMXAA).
• To achieve dual-zone programmed sono-STING immunotherapy (DPSSI) in both tumors and tdLNs.
• To investigate the efficacy of this strategy in eradicating primary tumors and suppressing metastatic dissemination.

Main Methods:

• In situ polymerization to engineer OPD@PSF nanoconverters.
• Peritumoral administration for preferential accumulation in tumors (EPR effect) and tdLNs (lymphatic drainage).
• High-power ultrasound (US) at the tumor site for sonodynamic therapy (SDT) and low-power US at tdLNs for immune activation.
• Co-delivery of PpIX for ROS generation and DMXAA for STING activation.

Main Results:

• OPD@PSF demonstrated preferential accumulation in both tumors and tdLNs.
• High-power US induced ROS for SDT, triggering immunogenic cell death in tumors.
• Low-power US in tdLNs promoted immune cell activation and hindered lymphatic metastasis.
• DMXAA-mediated STING activation synergized with SDT to eradicate tumors and suppress metastasis.

Conclusions:

• The rationally designed OPD@PSF nanoconverter offers a novel nanotechnological strategy for synergistic breast cancer therapy.
• Dual-targeted delivery to tumors and tdLNs, combined with optimized US parameters, enhances treatment efficacy.
• This approach holds significant promise for clinical translation in treating breast cancer and preventing metastasis through systemic immune orchestration.