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A nanoplatform to boost multi-phases of cancer-immunity-cycle for enhancing immunotherapy
Journal of Controlled Release  (IF9.776),  Pub Date : 2021-10-14, DOI: 10.1016/j.jconrel.2021.10.011
Cuixia Zheng, Qingling Song, Hongjuan Zhao, Yueyue Kong, Lingling Sun, Xinxin Liu, Qianhua Feng, Lei Wang

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.