Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death.
10.1016/j.apsb.2021.07.025
- Author:
Xinping KUAI
1
;
Yuefei ZHU
2
;
Zheng YUAN
3
;
Shengyu WANG
4
;
Lin LIN
1
;
Xiaodan YE
5
;
Yiping LU
1
;
Yu LUO
6
;
Zhiqing PANG
2
;
Daoying GENG
1
;
Bo YIN
1
Author Information
1. Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
2. School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.
3. Department of Radiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China.
4. Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201800, China.
5. Department of Radiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
6. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, School of Chemical Science and Engineering, Shanghai 200092, China.
- Publication Type:Journal Article
- Keywords:
Dual-modality imaging;
Glutathione depletion;
High-intensity focused ultrasound;
Immunogenic cell death;
Manganese dioxide nanoparticles;
Nanoemulsions;
Tumor microenvironment
- From:
Acta Pharmaceutica Sinica B
2022;12(2):967-981
- CountryChina
- Language:English
-
Abstract:
Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.
