Mitochondria-targeting Au nanoclusters enhance radiosensitivity of cancer cells

Radiotherapy is an important technology for the clinical treatment of cancer, but the patients suffer from the severe side effects after exposure to radiation. There is an urgent need to develop theranostic agents with excellent imaging capability and effective radiosensitization in order to minimize X-ray irradiation. Herein, we report an approach to synthesize peptide-templated Au nanoclusters (AuNCs) for theranostic radiosensitization. A new peptide (CCYKFR) is designed for the preparation of AuNCs with uniform size distribution and fluorescence (656 nm) of high photostability. CCYKFR–AuNCs feature highly efficient targeting/accumulation on mitochondria after endocytosis. With a series of experiments, we demonstrate that CCYKFR–AuNCs irradiated by 4 Gy X-rays can introduce a burst of mitoROS and severe DNA damage leading to cancer cell death. This study presents an important strategy to design theranostic nanomaterials with improved radiosensitization for the development of new anti-cancer therapies.