A cuproptosis-inducing covalent organic framework synergizes with oncolytic virus for tumor radiotherapy.

A copper-based covalent organic framework combined with oncolytic virus enhances radiotherapy efficacy by inducing cuproptosis in radioresistant tumors, achieving durable immune responses.

• Why it matters: Radioresistance hampers the success of radiotherapy, and understanding mechanisms like cuproptosis offers new avenues to overcome this challenge and improve treatment outcomes.
• What they did: Researchers developed a radiation-responsive copper-incorporated covalent organic framework (COF‑Tpy‑Se‑Cu) and combined it with an oncolytic adenovirus, testing their synergy in tumor models with X-ray irradiation.
• The result: This combination triggered cuproptosis, boosted tumor cell death, remodeled the tumor microenvironment into a T-cell-inflamed state, and elicited systemic, long-lasting antitumor immunity in mice.