Calcium-deprivation-activated immune responses for solid tumor regression

Cancer immunotherapy is currently one of the most attractive therapeutics against hematological malignancies, but unfortunately, the outcomes remain unsatisfactory in most types of solid tumors, largely because of the immunosuppressive tumor microenvironment and hardly permeable barriers of solid tumors against immune cell infiltrations. Herein, we report a distinctive calcium-deprivation strategy for antitumoral-immune-response activations by establishing an extremely simple nanomedicine of ethylenediaminetetraacetate (EDTA)-loaded layered double hydroxide featuring an intratumoral mild-acidity-responsive EDTA release character, which enables Ca²⁺ deprivations from both the endoplasmic reticulum of innate immune cells once phagocytosed and the intercellular cadherins bridging tumor cells by EDTA chelation. Such dual Ca²⁺ deprivations by the nanomedicine result in the antitumoral phenotype polarizations of the innate macrophages and neutrophils and tumor permeability enhancement, consequently greatly enhancing the infiltrations/accumulations of the antitumor types of innate/adaptive immune cells in the solid tumor interiors.