Melanin-loaded CpG DNA hydrogel for modulation of tumor immune microenvironment

Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment, but this strategy has suffered from the lack of biodegradability of the photoresponsive materials. In this study, we aimed to develop biodegradable materials for photothermal immunotherapy. To this end, we designed a DNA CpG hydrogel (DH, generated by rolling-circle amplification), loaded it with bis-(3'-5')-cyclic dimeric guanosine monophosphate (G/DH), and coated the formulation with melanin (Mel/G/DH). Mel/G/DH exhibited a temperature increase upon near infrared (NIR) illumination. In vitro, Mel/G/DH plus NIR (808 nm) irradiation, induced the exposure of calreticulin on CT26 cancer cells, and significantly activated the maturation of dendritic cells (DC). In vivo, local administration of Mel/G/DH (+NIR) exerted photothermal killing of primary tumors and induced maturation of DC in lymph nodes. Treatment of primary tumors with Mel/G/DH(+NIR) prevented the growth of rechallenged tumors at a distant site. Survival was 100% in mice treated with Mel/G/DH(+NIR), 5-fold higher than the group treated with Mel/G(+NIR). Mel/G/DH(+NIR) treatment remodeled the immune microenvironment of distant tumors, increasing cytotoxic T cells and decreasing Treg cells. Taken together, the results of this study suggest the potential of Mel/G/DH as a platform for modulating tumor immune microenvironment aimed at preventing the recurrence of distant tumors.