A biomimetic oxygen-generating nanoplatform for enhanced sonodynamic immune activation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Sonodynamic therapy (SDT) efficacy is limited by tumor hypoxia, especially in breast cancer.
• Hypoxic tumors resist conventional treatments, necessitating novel therapeutic strategies.
• Developing oxygen-generating systems can overcome this limitation.

Purpose of the Study:

• To create a biomimetic nanoplatform for in-situ oxygen generation to enhance SDT.
• To evaluate the platform's tumor-targeting, hypoxia-alleviating, and therapeutic effects.
• To assess the platform's ability to modulate the tumor immune microenvironment.

Main Methods:

• Fabrication of poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-loaded with catalase and IR780, coated with 4T1 cancer cell membranes (CIP@4T1m NPs).
• In vitro and in vivo evaluation of tumor targeting, hypoxia relief, singlet oxygen generation, and antitumor efficacy.
• Assessment of immunogenic cell death (ICD) induction and immune response activation (dendritic cells, macrophages, T cells).

Main Results:

• CIP@4T1m NPs showed preferential accumulation in 4T1 tumors.
• The nanoplatform effectively alleviated tumor hypoxia and enhanced SDT-induced singlet oxygen production.
• Ultrasound treatment with CIP@4T1m NPs promoted ICD, modulated immune cell populations, and increased CD8+ T cell infiltration.

Conclusions:

• A biomimetic nanoplatform integrating homologous targeting and enzymatic oxygen generation enhances SDT efficacy.
• This strategy effectively mitigates hypoxia-associated limitations in breast cancer treatment.
• The approach shows potential for improving SDT performance and stimulating antitumor immunity.