Metabolic reprogramming nanomedicine potentiates colon cancer sonodynamic immunotherapy by inhibiting the CD39/CD73/ADO pathway.
10.1016/j.apsb.2025.03.046
- Author:
Yuanyuan ZHANG
1
;
Weiwei JIN
2
;
Zhichao DENG
1
;
Bowen GAO
1
;
Yuanyuan ZHU
1
;
Junlong FU
1
;
Chenxi XU
1
;
Wenlong WANG
1
;
Ting BAI
3
;
Lianying JIAO
1
;
Hao WU
1
;
Mingxin ZHANG
4
;
Mingzhen ZHANG
1
Author Information
1. School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China.
2. General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, China.
3. Department of Cardiovascular Medicine, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710077, China.
4. Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, China.
- Publication Type:Journal Article
- Keywords:
Ag2S quantum dots;
Anti-tumor immunity;
CD39/CD73/ADO pathway;
Colon cancer;
Immunogenic cell death;
Immunotherapy;
POM1;
Sonodynamic therapy
- From:
Acta Pharmaceutica Sinica B
2025;15(5):2655-2672
- CountryChina
- Language:English
-
Abstract:
Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.
