Hafnium oxide nanoparticles coated ATR inhibitor to enhance the radiotherapy and potentiate antitumor immune response

Nanomaterials as radioenhancer have been widely studied, which exhibits huge advantages in tumor radiotherapy. However, DNA damage repair in tumor cells leads to radioresistance and radiotherapy alone is difficult to effectively suppress metastatic tumor. Herein, a potential strategy is proposed to enhance the local radiotherapeutic effects and trigger systemic antitumor immunity by combining nano-radioenhancer with Ataxiatelangiectasia mutated and RAD3-related (ATR) kinase inhibitor (ATRi). In the design, the nanoradioenhancer can trigger severe damages to tumor cells, while ATRi prevents DNA repair, which markedly complementing the local radiotherapeutic efficacy. In addition, the strategy can efficiently trigger systemic antitumor immune response via driving immune cell infiltration and enhancing immunogenicity based on the cGAS-STING pathway. This study provides a new avenue for nanoparticles-mediated radiotherapy to trigger strong antitumor effect in both local and distant tumor sites.