Sequential Tumor Microenvironment Reprogramming by Nanoplatform Potentiates Sonodynamic-Chemodynamic Therapy and...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• The tumor microenvironment (TME) presents a significant challenge to effective breast cancer treatment.
• Developing strategies to overcome TME-mediated resistance is crucial for improving immunotherapy outcomes.

Purpose of the Study:

• To develop a modular nanoplatform for sequential reprogramming of the TME to enhance breast cancer immunotherapy.
• To investigate the combined therapeutic effects of sonodynamic and chemodynamic therapy in a breast cancer model.

Main Methods:

• Synthesis of a hybrid nanoparticle (MCC) with manganese dioxide (MnO2), calcium peroxide (CaO2), and chlorin e6 (Ce6).
• Camouflage of MCC with tumor cell membrane and conjugation of a PD-L1 antibody (αP) via a glutathione (GSH)-responsive fragment, forming MCC@TM-αP.
• Utilizing dual-targeting and sequential drug release mechanisms for targeted therapy and immune response activation.

Main Results:

• MCC@TM-αP demonstrated efficient tumor site enrichment through dual-targeting.
• The nanoplatform alleviated tumor hypoxia and amplified sonodynamic therapy efficacy.
• Combined sonodynamic and chemodynamic therapy effectively ablated tumors and reprogrammed the immunosuppressive TME.
• In vivo studies showed enhanced effector T cell infiltration and suppressed metastatic progression.

Conclusions:

• The developed nanoplatform offers a programmable approach to potentiate immunotherapy by sequentially addressing immunosuppressive mechanisms.
• This strategy holds promise for overcoming TME-driven resistance in breast cancer treatment.
• The study provides a novel therapeutic avenue for enhancing breast cancer immunotherapy and combating metastasis.