Efficient copper ion transport triggers in situ photothermia and cuproptosis for boosting colon cancer immunotherapy.

Abstract

Photothermal therapy (PTT) or cuproptosis based on copper ions is a crucial strategy for precise colon cancer treatment. The excessive demand for tumoral accumulation of copper ions is essential to realize cuproptosis and in situ PTT simultaneously. Herein, a biomimetic nanoplatform ZCESM@mem was fabricated to achieve an efficient copper ions transport for the combination of cuproptosis and in situ photothermal therapy. ZCESM@mem specifically targeted to tumors via the tumor biotaxis of macrophage membranes coating, and subsequently achieved endogenous H₂S-triggered in situ PTT with the generation of photothermal agent copper sulfide in special colon cancer microenvironment, resulting in direct hyperthermia ablation. Moreover, the degraded nanoplatform in acidic microenvironment released the copper ionophores elesclomol to accelerate the transport and accumulation of copper ions at mitochondria for inducing the PTT-promoted cuproptosis. The combined cuproptosis and PTT induced immunogenic cell death, activated the robust immune response and reprogrammed the immunosuppressive tumor microenvironment, demonstrating potent efficacy in inhibiting tumor proliferation and recurrence. Collectively, this study developed an efficient copper ion transport nanoplatform with integrated functions as cuproptosis and in situ endogenous H₂S-triggered PTT for boosting colon cancer immunotherapy.