A nanoplatform to boost multi-phases of cancer-immunity-cycle for enhancing immunotherapy

The failure of any phase in continuous multi-link immune response process can cause unsatisfactory outcomes, which might be improved by all-cancer-immunity-cycle boosted strategy. Herein, a nanoplatform Mn/CaCO3@PL/SLC is developed, which is based on palmitoyl ascorbate (PA)-liposome (PL) loaded wit...

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Bibliographic Details
Published in:Journal of controlled release 2021-11, Vol.339, p.403-415
Main Authors: Zheng, Cuixia, Song, Qingling, Zhao, Hongjuan, Kong, Yueyue, Sun, Lingling, Liu, Xinxin, Feng, Qianhua, Wang, Lei
Format: Article
Language:English
Subjects:
Humans
Immunogenic cell death
Immunotherapy
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating
Neoplasms - therapy
Tumor immunotherapy
Tumor Microenvironment
Tumor-immunity cycle
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Summary:The failure of any phase in continuous multi-link immune response process can cause unsatisfactory outcomes, which might be improved by all-cancer-immunity-cycle boosted strategy. Herein, a nanoplatform Mn/CaCO3@PL/SLC is developed, which is based on palmitoyl ascorbate (PA)-liposome (PL) loaded with Mn-doped CaCO3 nanoparticles (Mn/CaCO3 NPs) and carbonic anhydrase (CAIX) inhibitor SLC-0111. The nanoplatform comprehensively amplifies all immune stages including tumor-associated antigens (TAAs) release and presentation, T cells activation and infiltration, as well as tumor cells destruction. In detail, Mn-triggered lipid peroxidation facilitates TAAs release and subsequent T cells activation to initiate immunity cycle. Additionally, SLC-0111 and PA amplify the infiltration and tumor killing activity of these effector T cells. The former polarizes the immunosuppressive tumor microenvironment to an immune-active phenotype and the latter enhances the function of tumor-infiltrating T lymphocytes. Importantly, Mn augments the all-immunity-cycle by promoting cGAS-STING pathway activation. In summary, the Mn/CaCO3@PL/SLC nanoplatform is verified to boost anti-tumor immunity and achieve outstanding immunotherapeutic effects in eradicating tumor and preventing tumor metastasis. Such an all-cancer-immunity-cycle boosted strategy is meaningful for antitumor immunotherapy. The schematic diagram of Mn/CaCO3@PL/SLC NPs, which augments the all-immunity-cycle by inducing immunogenic cell death of tumor cells, polarizing the immunosuppresive tumor microenvironment and increasing the vitality of tumor-infiltrating T lymphocytes. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2021.10.011