Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 11, Pages 12960-12971Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c02011
Keywords
tumor microenvironment; extracellular matrix; nitric oxide; matrix metalloproteinases; multimodal synergistic therapy
Funding
- Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
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The BAGM nanozyme is an intelligent nanotheranostic platform with multiple therapeutic modalities, enhancing treatment efficacy through a cascade catalytic reaction in the tumor microenvironment.
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 is innovatively designed as a multimodal synergistic therapeutic paradigm that possesses both nitric oxide (NO) self-supplying and ECM degradation properties to reinforce the therapy effect by a tumor microenvironment (TME)-activatable cyclic cascade catalytic reaction. This theranostic nanoplatform is constructed by using polyethyleneimine-modified black phosphorus nanosheets as a fishnet to attach L-Arginine (L-Arg) and glucose oxidase (GOx) and then depositing mini-sized MnO2 nanosheets (MNs) on the surface by a facile situ biomineralization method. As an intelligent switch, the MNs can effectively trigger the cascade reaction by disintegrating intracellular H2O2 to release O-2. Then, the conjugated GOx can utilize O-2 production to catalyze intracellular glucose to generate H2O2, which not only starves the tumor cells but also promotes oxidation of L-Arg to NO. Thereafter, matrix metalloproteinases will be activated by NO production to degrade the dense ECM and transform matrix collagen into a loose state. In turn, a loose ECM can enhance the accumulation of the BAGM nanozyme and thereby reinforce synergistic photothermal therapy/starvation therapy/NO gas therapy. Both in vitro and in vivo results indicate that the TME-tunable BAGM therapeutic nanoplatform with cascade anticancer property and satisfactory biosecurity shows potential in nanomedicine.
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