Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation

Abstract The direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapy but remains challenging. Herein, we report a one‐pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self‐assembled through a time‐resolved lamellar growth mechanism feature an openworked core and a dendritic shell, both constructed by silica nanosheets of ≈3 nm. With a large pore size, high surface area and pore volume, ODMSNs exhibited a high loading capacity (>0.7 g g −1 ) of lactate oxidase (LOX) and enabled intratumoral lactate depletion by >99.9 %, leading to anti‐angiogenesis, down‐regulation of vascular endothelial growth factor, and increased tumor hypoxia. The latter event facilitates the activation of a co‐delivered prodrug for enhancing anti‐tumor and anti‐metastasis efficacy. This study provides an innovative nano‐delivery system and demonstrates the first example of direct lactate‐depletion‐enabled chemotherapy.