NIR-II Light-Triggered Electron Flow Initiates Cuproptosis-Centered Thermoelectric-Immunotherapy for Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Cuproptosis, a copper-dependent cell death, shows promise in oncology.
• Current limitations include inefficient generation of bioactive Cu+ species within tumors.

Purpose of the Study:

• To develop a nanoreactor for spatiotemporally controlled Cu+ production to enhance cancer therapy.
• To investigate the thermoelectric-immunological cascade for cancer treatment and immunotherapy.

Main Methods:

• Fabrication of a thermoelectric nanoreactor (Te@PDA-CuII) using tellurium nanorods and polydopamine.
• Activation via 1064 nm light irradiation to generate directional electron flow and reduce Cu2+ to Cu+.
• Assessment of cuproptosis induction, immunogenic cell death (ICD), and therapeutic efficacy in breast cancer models.

Main Results:

• The nanoreactor efficiently produces Cu+ in situ, triggering cuproptosis via DLAT aggregation and Fe-S cluster destabilization.
• Cuproptosis induction led to immunogenic cell death (ICD), promoting dendritic cell maturation and T cell infiltration.
• The nanoreactor eradicated primary tumors and suppressed distant metastases when combined with aPD-1 blockade, establishing immune memory.

Conclusions:

• A physical energy-driven strategy for precise cuproptosis activation was established.
• The thermoelectric nanoreactor amplifies cancer immunotherapy by inducing ICD and synergistic effects with checkpoint blockade.
• This approach holds potential for treating primary and metastatic cancers.