Tumor Microenvironment-Activatable Cyclic Cascade Reaction to Reinforce Multimodal Combination Therapy by Destroying the Extracellular Matrix

• DOI: 10.1021/acsami.1c02011
• Publication Date: 2021-03-15T17:51:32Z
• Authors: Yutian Su; Xichen Zhang; Liling Lei; Baolei Liu; Shishan Wu; Jian Shen
• Keywords: Glucose oxidase; Surface Modification

The optimal therapy effect of tumors is frequently restricted by the dense extracellular matrix (ECM) and anoxia. Herein, an intelligent BPNs-Arg-GOx@MnO2 (BAGM) nanozyme innovatively designed as a multimodal synergistic therapeutic paradigm that possesses both nitric oxide (NO) self-supplying ECM degradation properties to reinforce tumor microenvironment (TME)-activatable cyclic cascade catalytic reaction. This theranostic nanoplatform constructed using polyethyleneimine-modified black phosphorus nanosheets "fishnet" attach l-Arginine (l-Arg) glucose oxidase (GOx) then depositing mini-sized MnO2 (MNs) on surface facile situ biomineralization method. As "switch", MNs can effectively trigger reaction disintegrating intracellular H2O2 release O2. Then, conjugated GOx utilize O2 production catalyze generate H2O2, which not only starves cells but also promotes oxidation l-Arg NO. Thereafter, metalloproteinases will be activated NO degrade transform collagen into loose state. In turn, enhance accumulation BAGM thereby photothermal therapy/starvation therapy/NO gas therapy. Both in vitro vivo results indicate TME-tunable with anticancer property satisfactory biosecurity shows potential nanomedicine.