细胞外基质
材料科学
级联
肿瘤微环境
癌症研究
细胞外
基质(化学分析)
纳米技术
生物物理学
细胞生物学
化学工程
肿瘤细胞
生物
复合材料
工程类
作者
Yutian Su,Xichen Zhang,Liling Lei,Baolei Liu,Shishan Wu,Jian Shen
标识
DOI:10.1021/acsami.1c02011
摘要
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 O2. Then, the conjugated GOx can utilize O2 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI