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-Fe(0)@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 Fe(0) nanoparticle (Fe(0)NP) was anchored in the inner cavity of glucose oxidase (GOx) to form iron-mineralized glucose oxidase (GOx-Fe(0)) as a potential tumor therapeutic nanocatalyst. Moreover, erythrocyte membrane cloaking delivery of GOx-Fe(0) in vivo was designed to effectively accumulate ultra-small GOx-Fe(0) at tumor site. Results: GOx-Fe(0)@EM-A had satisfactory biocompatibility and light-trigged release efficiency. Erythrocyte membrane cloaking of GOx-Fe(0)@EM-A not only prolongs blood circulation but also protects in vivo enzyme activity of GOx-Fe(0); Tumor targeting of GOx-Fe(0)@EM-A endowed preferential accumulation at tumor site. After NIR light irradiation at tumor site, erythrocyte membrane of GOx-Fe(0)@EM-A was ruptured to achieve light-driven release and tumor deep penetration of ultra-small nanosize GOx-Fe(0) by the photothermal effect of ICG. Then, GOx-Fe(0) 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.