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

作者：Yutian Su, Xichen Zhang, Liling Lei, Baolei Liu, Shishan Wu, Jian Shen · 发表于：ACS Applied Materials & Interfaces · 年份：2021 · DOI：10.1021/acsami.1c02011 · 被引用次数：55 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Nanoparticle-Based Drug Delivery

The optimal therapy effect of tumors is frequently restricted by the dense extracellular matrix (ECM) and anoxia. Herein, an intelligent BPNs-Arg-GOx@MnO 2 (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 MnO 2 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 H 2 O 2 to release O 2 . Then, the conjugated GOx can utilize O 2 production to catalyze intracellular glucose to generate H 2 O 2, 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 propert...