A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 30 vom: 25. Juli, Seite e2404901
1. Verfasser: Li, Feiyu (VerfasserIn)
Weitere Verfasser: Zhu, Peipei, Zheng, Bingzhu, Lu, Zijie, Fang, Chao, Fu, Yike, Li, Xiang
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article bacteria biohybrids engineering nanozymes tumor therapy lactate 2-monooxygenase EC 1.13.12.4 Mixed Function Oxygenases EC 1.- mehr... Tirapazamine 1UD32YR59G Hydrogen Peroxide BBX060AN9V ZIF-8 metal-organic framework Metal-Organic Frameworks Imidazoles Lactic Acid 33X04XA5AT Hydroxyl Radical 3352-57-6 Antineoplastic Agents
Beschreibung
Zusammenfassung:© 2024 Wiley‐VCH GmbH.
Intrinsic characteristics of microorganisms, including non-specific metabolism sites, toxic byproducts, and uncontrolled proliferation constrain their exploitation in medical applications such as tumor therapy. Here, the authors report an engineered biohybrid that can efficiently target cancerous sites through a pre-determined metabolic pathway to enable precise tumor ablation. In this system, DH5α Escherichia coli is engineered by the introduction of hypoxia-inducible promoters and lactate oxidase genes, and further surface-armored with iron-doped ZIF-8 nanoparticles. This bioengineered E. coli can produce and secrete lactate oxidase to reduce lactate concentration in response to hypoxic tumor microenvironment, as well as triggering immune activation. The peroxidase-like functionality of the nanoparticles extends the end product of the lactate metabolism, enabling the conversion of hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals. This, coupled with the transformation of tirapazamine loaded on nanoparticles to toxic benzotriazinyl, culminates in severe tumor cell ferroptosis. Intravenous injection of this biohybrid significantly inhibits tumor growth and metastasis
Beschreibung:Date Completed 25.07.2024
Date Revised 25.07.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202404901