Tumor-activatable ultrasmall nanozyme generator for enhanced penetration and deep catalytic therapy.

Abstract:

:Tumor-activatable ultrasmall nanozyme generation is an unprecedented strategy to overcome intrinsically fatal defects of traditional reactive oxygen species (ROS)-based nanoagents for deep tumor penetration, including limited tissue-penetrating depth of external energy, heavy reliance on oxygen and nonspecific toxicity of therapeutic agents. Here, based on the cascade reaction between glucose oxidase (GOx) and ultrasmall peroxidase nanozyme embedded into acid-dissociable zeolitic imidazolate framework-8 (ZIF-8), such a tumor-activatable ultrasmall nanozyme generator is designed for enhanced penetration and deep catalytic therapy. With the aid of mildly acidic tumor microenvironment, the produced gluconic acid from intratumoral glucose can gradually induce the dissociation of ZIF-8 to release ultrasmall peroxidase nanozyme with significant intratumoral penetration. On the other hand, the generated hydrogen peroxide with relatively long-life can be subsequently catalyzed by penetrated peroxidase nanozyme into toxic hydroxyl radicals for deep catalytic therapy. In this way, the well-designed nanoplatform not only can greatly enhance tumor penetration but also directly induce exogenous ROS without oxygen participation and external energy input, thereby thoroughly avoiding the inactivation of traditional ROS-based nanoagents in the extremely hypoxic tumor center and finally resulting in remarkable deep catalytic therapy.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Liu X,Liu Z,Dong K,Wu S,Sang Y,Cui T,Zhou Y,Ren J,Qu X

doi

10.1016/j.biomaterials.2020.120263

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

120263

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(20)30509-3

journal_volume

258

pub_type

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