Self-activated <i>in vivo</i> therapeutic cascade of erythrocyte membrane-cloaked iron-mineralized enzymes

Abstract

Biomineralization of enzymes for <i>in vivo</i> 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 <i>in vivo</i> cascade to generate sufficient high toxic •OH at tumor site. <b>Methods</b>: 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-Fe⁰<i>in vivo</i> was designed to effectively accumulate ultra-small GOx-Fe⁰ at tumor site. <b>Results</b>: 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 <i>in vivo</i> 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 <i>in vivo</i> cascade to effectively eradicate tumor by producing the highly cumulative and deeply penetrating •OH at tumor site. <b>Conclusion</b>: 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.