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 center dot OH at tumor site. Methods: An ultra-small Fe-0 nanoparticle ((FeNP)-N-0) 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 center dot OH at tumor site. Conclusion: Tumor-targeted erythrocyte membrane-cloaked iron-mineralized glucose oxidase (GOx-Fe-0@EM-A) exhibits a promising strategy for striking antitumor efficacy by light-driven tumor deep penetration and self-activated therapeutic cascade.