Self-activated in vivo therapeutic cascade of erythrocyte membrane-cloaked iron-mineralized enzymes.

Biomineralization of enzymes for in vivo diagnosis and treatment of diseases remain a considerable challenge, due to their severe reaction conditions and complicated physiological environment. Herein, we reported a biomimetic enzyme cascade delivery nanosystem, tumor-targeted erythrocyte membrane (EM)-cloaked iron-mineralized glucose oxidases (GOx-Fe0@EM-A) for enhancing anticancer efficacy by self-activated in vivo cascade to generate sufficient high toxic •OH at tumor site. Methods: An ultra-small Fe0 nanoparticle (Fe0NP) was anchored in the inner cavity of glucose oxidase (GOx) to form iron-mineralized glucose oxidase (GOx-Fe0) as a potential tumor therapeutic nanocatalyst. Moreover, erythrocyte membrane cloaking delivery of GOx-Fe0in vivo was designed to effectively accumulate ultra-small GOx-Fe0 at tumor site. Results: GOx-Fe0@EM-A had satisfactory biocompatibility and light-trigged release efficiency. Erythrocyte membrane cloaking of GOx-Fe0@EM-A not only prolongs blood circulation but also protects in vivo enzyme activity of GOx-Fe0; Tumor targeting of GOx-Fe0@EM-A endowed preferential accumulation at tumor site. After NIR light irradiation at tumor site, erythrocyte membrane of GOx-Fe0@EM-A was ruptured to achieve light-driven release and tumor deep penetration of ultra-small nanosize GOx-Fe0 by the photothermal effect of ICG. Then, GOx-Fe0 occurred self-activated in vivo cascade to effectively eradicate tumor by producing the highly cumulative and deeply penetrating •OH at tumor site. Conclusion: Tumor-targeted erythrocyte membrane-cloaked iron-mineralized glucose oxidase (GOx-Fe0@EM-A) exhibits a promising strategy for striking antitumor efficacy by light-driven tumor deep penetration and self-activated therapeutic cascade.

Liu W ，Ruan ML ，Liu L ，Ji X ，Ma Y ，Yuan P ，Tang G ，Lin H ，Dai J ，Xue W ... -  《Theranostics》

Erythrocyte Membrane Cloaked Metal-Organic Framework Nanoparticle as Biomimetic Nanoreactor for Starvation-Activated Colon Cancer Therapy.

Zhang L ，Wang Z ，Zhang Y ，Cao F ，Dong K ，Ren J ，Qu X ... -  《-》

MOF-Immobilized Two-in-One Engineered Enzymes Enhancing Activity of Biocatalytic Cascade for Tumor Therapy.

Biocatalytic systems based on enzyme cascade reactions have attracted growing interest in the field of biocatalytic medicine. However, it is a major challenge to reasonably construct enzyme cascade reactions with high stability, selectivity, and catalytic efficiency for the in vivo biocatalytic application. Herein, two-in-one engineered glucose oxidase (GOx-Fe0 ) is fabricated by a biomineralization strategy, through which a nanozyme (Fe0 NP) is anchored within the inner cavity of GOx. Then, GOx-Fe0 is immobilized in a pH-sensitive metal-organic framework (MOF) zeolitic imidazolate framework-8 (ZIF-8) to establish a stable and effective MOF-immobilized two-in-one engineered enzyme, GOx-Fe0 @ZIF-8. In vitro studies show that GOx-Fe0 @ZIF-8 exhibits excellent stability and high pH/glucose selectivity, and the shorter spacing between cascade enzymes can increase the cascade throughput and effectively improve the reaction efficiency of the enzyme cascade. In vivo experiments exhibit that GOx-Fe0 @ZIF-8 solves the instability and systemic toxicity of free enzymes, and achieves deep tumor penetration and significant chemodynamic therapeutic efficacy through a pH/glucose-selective enzyme cascade reaction in tumor site. Taken together, such an orchestrated enzyme engineering strategy can effectively improve enzyme stability, selectivity, and enzyme cascade reaction efficiency via chemical transformations, and also provide a promising strategy for the application of biocatalytic cascade reactions in vivo.

Yang C ，Liu W ，Chen S ，Zong X ，Yuan P ，Chen X ，Li X ，Li Y ，Xue W ，Dai J ... -  《-》

Glucose Oxidase-Integrated Metal-Organic Framework Hybrids as Biomimetic Cascade Nanozymes for Ultrasensitive Glucose Biosensing.

Xu W ，Jiao L ，Yan H ，Wu Y ，Chen L ，Gu W ，Du D ，Lin Y ，Zhu C ... -  《-》

Erythrocyte Membrane-Camouflaged PCN-224 Nanocarriers Integrated with Platinum Nanoparticles and Glucose Oxidase for Enhanced Tumor Sonodynamic Therapy and Synergistic Starvation Therapy.

Bao Y ，Chen J ，Qiu H ，Zhang C ，Huang P ，Mao Z ，Tong W ... -  《-》