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


ABSTRACT: 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-Fe0 in 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.

SUBMITTER: Liu W 

PROVIDER: S-EPMC7019169 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Liu Wen W   Ruan Miao-Liang ML   Liu Lamei L   Ji Xin X   Ma Yandong Y   Yuan Pengfei P   Tang Guoheng G   Lin Hongsheng H   Dai Jian J   Xue Wei W  

Theranostics 20200112 5


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-Fe<sup>0</sup>@EM-A) for enhancing anticancer efficacy by self-activated <i>in vivo</i> cascade to generate sufficient high toxic •OH at tumor  ...[more]

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