DNA Nanocluster Combined with one-shot Radiotherapy Augment Cancer Immunotherapy Efficiency.

Immunotherapy show immense promise for improving cancer treatment. Combining immunotherapy with radiotherapy provides conspicuous advantage due to its enhanced abscopal effect. However, established immune tolerance mechanisms in the tumor microenvironment can hamper the generation of sufficient abscopal effect. Herein, we designed a type of DNA nanocluster (DNAnc) that was self-assembled by CpG ODNs loaded Y-shaped double stranded DNA vector based on the unique complementary base-pairing rules. The unique structure of DNAnc made it load more than about 8125.5 ± 822.5 copies of CpG ODNs within one single nanostructure, which effectively increased resistance to nuclease degradation and elevated the efficiency of repolarizing macrophages to a M1-like phenotype. Mechanistic studies revealed that more DNAnc were endocytosed by macrophages at the cancer tissue and repolarize macrophages to elicit a robust abscopal effect with the accumulation of macrophages induced by radiotherapy, generating potent, long-term and durable antitumor immunity for the inhibition of tumor metastasis and the prevention of tumour recurrence, which provides a novel strategy to boost cancer immunotherapy. This article is protected by copyright. All rights reserved.