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

• Main Authors: Xinping Kuai (Author), Yuefei Zhu (Author), Zheng Yuan (Author), Shengyu Wang (Author), Lin Lin (Author), Xiaodan Ye (Author), Yiping Lu (Author), Yu Luo (Author), Zhiqing Pang (Author), Daoying Geng (Author), Bo Yin (Author)
• Format: Book
• Published: Elsevier, 2022-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2211-3835; 10.1016/j.apsb.2021.07.025
• Keywords: Immunogenic cell death; Nanoemulsions; Manganese dioxide nanoparticles; Glutathione depletion; Dual-modality imaging; High-intensity focused ultrasound; Therapeutics. Pharmacology; RM1-950
• Source: Acta Pharmaceutica Sinica B, Vol 12, Iss 2, Pp 967-981 (2022)

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.