Autophagy-Inducing MoO_3-x Nanowires Boost Photothermal-Triggered Cancer Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Autophagy can suppress cancer therapy by releasing tumor antigens and inducing immunogenic cell death (ICD).
• Developing effective inducers of cytotoxic autophagy is crucial for innovative cancer treatments.

Purpose of the Study:

• To develop novel molybdenum trioxide-x nanowires (MoO3-x NWs) with high oxygen vacancy and photothermal responsivity.
• To investigate the potential of MoO3-x NWs in inducing cytotoxic autophagy and severe ICD for enhanced cancer immunotherapy.

Main Methods:

• Synthesis of MoO3-x NWs with high oxygen vacancy and strong photothermal properties.
• Combination of MoO3-x NWs with photothermal therapy (PTT) and PD-1 immune checkpoint blockade.
• Evaluation of autophagy induction, tumor antigen release, dendritic cell maturation, T cell activation, and immune cell polarization in vivo.

Main Results:

• MoO3-x NWs combined with PTT effectively induced autophagy, promoting tumor antigen release and dendritic cell maturation.
• This combination therapy activated cytotoxic T lymphocyte (CTL)-mediated adaptive immunity.
• Combined treatment with PD-1 blockade modulated macrophages and T cells, alleviating immunosuppression and intensifying anti-tumor activity.

Conclusions:

• MoO3-x NWs are effective inducers of cytotoxic autophagy and ICD, enhancing photothermal immunotherapy.
• The strategy enhances anti-tumor immune responses by promoting antigen presentation and modulating the tumor microenvironment.
• This study provides a mechanistic understanding for using MoO3-x NWs in advanced cancer treatment strategies.