Ultrasound-triggered and glycosylation inhibition-enhanced tumor piezocatalytic immunotherapy
Yinying Pu, Bangguo Zhou, Jinhong Bing, Liang Wang, Mingqi Chen, Yucui Shen, Shuang Gao, Min Zhou, Wencheng Wu, Jianlin Shi
Abstract
Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A “hot” tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation. N-glycosylation has a significant role in immunosuppressive tumor microenvironment (TME). Here, the authors design an injectable ROS-sensitive hydrogel scaffold co-delivering piezocatalyst BiFeO3 and glucose/mannose analog 2-deoxy-d-glucose alleviating N-glycosylation inhibition and thereby effectively stimulating immune responses within TME.