Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases

Kaiwang Xu; Huang Yang; Jinghua Fang; Kaijie Qiu; Haotian Shen; Guanrui Huang; Qiangqiang Zheng; Canlong Wang; Tengjing Xu; Xinning Yu; Jiajie Wang; Yunting Lin; Jiacheng Dai; Yuting Zhong; Hongyun Song; Sunan Zhu; Siheng Wang; Zhuxing Zhou; Guang Yang; Zhengwei Mao; Zongyou Pan; Xuesong Dai

doi:10.1016/j.bioactmat.2024.02.022

Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases

Bioact Mater. 2024 Mar 8:36:272-286. doi: 10.1016/j.bioactmat.2024.02.022. eCollection 2024 Jun.

Authors

Kaiwang Xu^{1

2

3

4}, Huang Yang⁵, Jinghua Fang^{1

2

3

4}, Kaijie Qiu^{1

2

3

4}, Haotian Shen⁶, Guanrui Huang⁶, Qiangqiang Zheng⁷, Canlong Wang^{1

2

3

4}, Tengjing Xu^{1

2

3

4}, Xinning Yu^{1

2

3

4}, Jiajie Wang^{1

2

3

4}, Yunting Lin^{1

2

3

4}, Jiacheng Dai^{1

2

3

4}, Yuting Zhong^{1

2

3

4}, Hongyun Song^{1

2

3

4}, Sunan Zhu^{1

2

3

4}, Siheng Wang^{1

2

3

4}, Zhuxing Zhou^{1

2

3

4}, Guang Yang^{1

2

3

4}, Zhengwei Mao^{5

8}, Zongyou Pan^{1

2

3

4}, Xuesong Dai^{1

2

3

4}

Affiliations

¹ Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
² Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
³ Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
⁴ Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, China.
⁵ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
⁶ Zhejiang University, Hangzhou, 310058, China.
⁷ Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310000, China.
⁸ Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Abstract

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Keywords: Anti-inflammation; Autoimmune inflammatory diseases; Nanoliposome; Pyroptosis; Responsive drug delivery.