Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Xinping Kuai; Yuefei Zhu; Zheng Yuan; Shengyu Wang; Lin Lin; Xiaodan Ye; Yiping Lu; Yu Luo; Zhiqing Pang; Daoying Geng; Bo Yin

doi:10.1016/j.apsb.2021.07.025

Perfluorooctyl bromide nanoemulsions holding MnO₂ nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Acta Pharm Sin B. 2022 Feb;12(2):967-981. doi: 10.1016/j.apsb.2021.07.025. Epub 2021 Jul 31.

Authors

Xinping Kuai¹, Yuefei Zhu², Zheng Yuan³, Shengyu Wang⁴, Lin Lin¹, Xiaodan Ye⁵, Yiping Lu¹, Yu Luo⁶, Zhiqing Pang², Daoying Geng¹, Bo Yin¹

Affiliations

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.

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.

Keywords: Dual-modality imaging; Glutathione depletion; High-intensity focused ultrasound; Immunogenic cell death; Manganese dioxide nanoparticles; Nanoemulsions; Tumor microenvironment.