Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, People's Republic of China.
Institute of Analysis and Testing, Beijing Academy of Science and Technology (Beijing Center for Physical and Chemical Analysis), Beijing 100089, People's Republic of China.
ACS Appl Mater Interfaces. 2022 Oct 26;14(42):47472-47481. doi: 10.1021/acsami.2c14957. Epub 2022 Oct 13.
Pyroptosis is a new type of regulated cell death that is of great interest for developing new strategies for treating cancers. This potential is however greatly limited by the low efficiency and selectivity of current strategies to regulate cancer cell pyroptosis. Herein, we report biodegradable metal-organic frameworks (MOFs) for intracellular delivery of glucose oxidase (GOx) that promotes cascade biocatalysis inside cells and selectively induces cancer cell pyroptosis. We show that the self-assembly of Cu and 4,4'-azobisbenzoic acid along with GOx affords protein-encapsulated GOx@Cu MOF that efficiently delivers GOx into cells. In addition, the tumor-cell-overexpressed NAD(P)H quinone dehydrogenase 1 (NQO1) can trigger the reduction of 4,4'-azobisbenzoic acid and the degradation of GOx@Cu MOF, releasing GOx to catalyze glucose oxidation and produce excessive hydrogen peroxide (HO) intracellularly. Furthermore, released Cu from Cu MOF could be reduced to Cu by intracellular glutathione (GSH), promoting Fenton-like reaction with HO to continuously generate a hydroxyl radical that induces cancer cell pyroptosis and prohibits tumor cell growth. We anticipate the strategy of harnessing biodegradable MOFs for protein delivery, and intracellular biocatalysis provides a powerful approach to regulate tumor cell pyroptosis for advanced therapeutic development.
细胞焦亡是一种新型的调控性细胞死亡，对于开发治疗癌症的新策略具有重要意义。然而，当前调控癌细胞焦亡的策略效率和选择性较低，极大地限制了这一潜力的发挥。在此，我们报告了一种用于细胞内递送葡萄糖氧化酶（GOx）的可生物降解的金属-有机框架（MOF），该策略可促进细胞内级联生物催化，并选择性诱导癌细胞焦亡。我们表明，Cu 和 4,4'-偶氮二苯甲酸与 GOx 自组装可提供蛋白质包封的 GOx@Cu MOF，可有效地将 GOx 递送到细胞内。此外，肿瘤细胞过表达的烟酰胺腺嘌呤二核苷酸（磷酸）醌脱氢酶 1（NQO1）可触发 4,4'-偶氮二苯甲酸的还原和 GOx@Cu MOF 的降解，释放出 GOx 以催化葡萄糖氧化并在细胞内产生过量的过氧化氢（HO）。此外，细胞内谷胱甘肽（GSH）可将 Cu MOF 中释放的 Cu 还原为 Cu，促进与 HO 的芬顿样反应，持续生成羟基自由基，诱导癌细胞焦亡并抑制肿瘤细胞生长。我们预计利用可生物降解的 MOF 进行蛋白质递送的策略，以及细胞内生物催化为调控肿瘤细胞焦亡提供了一种强大的方法，为先进的治疗开发提供了可能。
