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 () and Jianlin Shi ()
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Yinying Pu: Chinese Academy of Sciences
Bangguo Zhou: Zhejiang University
Jinhong Bing: Chinese Academy of Sciences
Liang Wang: Chinese Academy of Sciences
Mingqi Chen: Shanghai Fourth People’s Hospital to Tongji University
Yucui Shen: Shanghai Fourth People’s Hospital to Tongji University
Shuang Gao: Shanghai Fourth People’s Hospital to Tongji University
Min Zhou: Shanghai Fourth People’s Hospital to Tongji University
Wencheng Wu: Chinese Academy of Sciences
Jianlin Shi: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53392-1

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