A Cascade Nanoreactor of Metal‐Protein‐Polyphenol Capsule for Oxygen‐Mediated Synergistic Tumor Starvation and Chemodynamic Therapy. Issue 5 (27th November 2022)

• Record Type: Journal Article
• Authors: Yu, Qiao; Zhou, Jie; Song, Juan; Zhou, Hong; Kang, Bin; Chen, Hong‐Yuan; Xu, Jing‐Juan
• Is Part Of: Small. Volume 19:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-27
• Subjects: cascade nanoreactors -- hemoglobin -- metal‐protein‐polyphenol capsules -- synergistic therapy; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202206592
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)‐mediated glycolysis is oxygen‐dependent, the cascade reaction based on GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H2 O2 into O2, starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close‐loop strategy for on demand H2 O2 and O2 delivery, release, and recycling is proposed. The nanoreactor (metal‐protein‐polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O2 consumption and the produced H2 O2 reacts with Hb to produce highly cytotoxic hydroxyl radicals (OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen‐mediated synergistic starvation therapy and chemodynamic therapy. Abstract : A tandem nanoreactor that responds to intracellular adenosine triphosphate and glutathione is designed through introducing native protein, glucose oxidase, and hemoglobin, into protein‐polyphenol networks. The artificial enzyme can trigger glycolysis and Fenton reaction in tumor tissue. Simultaneous release of oxygen and free radicals reinforces tumor starvation and chemodynamic therapy.