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

Minghao Sun¹, Yuhang Huang¹, Yun Hou¹

¹State Key Laboratory of Natural Medicines, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, China.

Small (Weinheim an Der Bergstrasse, Germany)

|April 29, 2026

Summary

This summary is machine-generated.

This study introduces a dual-targeting nanoconverter for breast cancer therapy. It effectively delivers agents to tumors and lymph nodes, enhancing treatment and suppressing metastasis through sono-immunotherapy.

Keywords:

controllable drug release in situ polymerization nanomicelle sono‐STING immunotherapy ultrasonic nanoconverter

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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.