Review of clinical applications of radiation-enhancing nanoparticles

•Inorganic nanoparticles activated by radiotherapy (RT) increase dose deposition within cancer cells compared to RT alone.•Recently, clinical evidence of the radiation-enhancing effects of NP has emerged.•Two radio-enhancement NP are currently under investigation in clinical trials: hafnium oxide NP and gadolinium-based NP.•So far, 229 patients have been treated with NP and RT for soft tissue sarcoma, head and neck cancers or liver cancer.•Intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma. Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. We searched the literature in English and French on PubMed up to October 2019. The search term was “nanoparticle” AND “radiotherapy”, yielding 1270 results. The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.