A Bimodal MRI-Traceable Nanozyme with Immune-Activated Capability for Immunotherapy of Lung Metastases

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Cancer therapy faces challenges from tumor hypoxia, high glutathione (GSH) levels in the tumor microenvironment (TME), and metastasis.
• Advanced diagnostic and therapeutic strategies are needed to overcome these limitations and improve treatment outcomes.

Purpose of the Study:

• To design multifunctional manganese-based nanoparticles (FMBI NPs) with nanozyme activities and GSH-depleting capabilities to remodel the TME and enhance cancer therapy.
• To investigate the potential of FMBI NPs to inhibit tumor metastasis and enable noninvasive imaging for monitoring therapeutic efficacy.

Main Methods:

• Fabrication of multifunctional manganese-based nanoparticles (FMBI NPs) with integrated nanozyme activities and GSH-depleting properties.
• Evaluation of FMBI NPs' ability to release Mn ions, modulate tumor stroma, activate the cGAS-STING pathway, and induce immunogenic cell death (ICD) in cancer cells.
• Assessment of FMBI NPs' efficacy in inhibiting lung metastasis and enabling 1H and 19F MRI for *in vivo* tumor visualization and therapeutic monitoring.

Main Results:

• FMBI NPs effectively depleted GSH and remodeled the TME, leading to enhanced cancer cell death.
• The released Mn ions modulated the tumor stroma and activated the cGAS-STING pathway, promoting immunogenic cell death.
• Systemic immune activation by FMBI NPs significantly inhibited lung metastasis and allowed for noninvasive monitoring of tumor treatment via MRI.

Conclusions:

• FMBI NPs represent a promising multifunctional nanoplatform for cancer therapy by remodeling the TME, inhibiting metastasis, and facilitating MRI-based diagnosis and treatment monitoring.
• This approach offers a novel strategy for improving cancer treatment outcomes through combined therapeutic and diagnostic capabilities.