School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Qixia District, Nanjing 210023, China.
National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing Normal University, Nanjing 210046, China.
ACS Appl Mater Interfaces. 2021 Mar 24;13(11):12960-12971. doi: 10.1021/acsami.1c02011. Epub 2021 Mar 15.
The optimal therapy effect of tumors is frequently restricted by the dense extracellular matrix (ECM) and anoxia. Herein, an intelligent BPNs-Arg-GOx@MnO (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 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 HO to release O. Then, the conjugated GOx can utilize O production to catalyze intracellular glucose to generate HO, 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.
肿瘤的最佳治疗效果经常受到致密的细胞外基质（ECM）和缺氧的限制。在此，创新性地设计了一种智能 BPNs-Arg-GOx@MnO（BAGM）纳米酶，作为一种具有一氧化氮（NO）自供给和 ECM 降解特性的多模式协同治疗范式，通过肿瘤微环境（TME）激活的循环级联催化反应来增强治疗效果。该治疗诊断纳米平台由聚乙烯亚胺修饰的黑磷纳米片作为“渔网”构建而成，用于附着 l-精氨酸（l-Arg）和葡萄糖氧化酶（GOx），然后通过简便的原位生物矿化方法在表面沉积小型 MnO 纳米片（MNs）。作为一种智能“开关”，MNs 可以通过分解细胞内的 HO 有效触发级联反应，从而释放 O。然后，共轭的 GOx 可以利用 O 生产来催化细胞内的葡萄糖生成 HO，这不仅使肿瘤细胞饥饿，还促进 l-Arg 氧化生成 NO。此后，NO 生成将激活基质金属蛋白酶来降解致密的 ECM，并将基质胶原蛋白转化为松散状态。体外和体内结果均表明，具有级联抗癌特性和令人满意的生物安全性的 TME 可调 BAGM 治疗纳米平台在纳米医学中具有潜力。
