期刊
JOURNAL OF CONTROLLED RELEASE
卷 339, 期 -, 页码 335-349出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.09.041
关键词
Glucose oxidase; Oxygen supply; Cascade reaction; Microneedles; Cancer therapy
资金
- National Natural Science Foundation [81803466]
- Key Areas Research and Development Program of Guangdong Province [2019B020204002]
- Key Areas Research and Development Program of Guangzhou [202007020006]
A strategy of cascade reaction-enhanced combined therapy based on oxygen-evolving multifunctional nanoreactors is proposed for tumor therapy. Immobilizing GOx and CAT in metal-organic frameworks via biomimetic mineralization enhances enzyme stability and improves efficacy in tumor treatment. The nanoreactors, delivered by microneedles, achieve efficient tumor accumulation and strengthen antitumor efficacy without obvious side effects.
Starvation therapy based on glucose oxidase (GOx) has attracted considerable attention in tumor treatment. However, several shortcomings severely hinder its further applications, including limited therapeutic efficacy, poor enzyme stability, and potential side effects. Herein, a strategy of cascade reaction-enhanced combined therapy based on the oxygen-evolving multifunctional nanoreactors is proposed for tumor therapy. The GOx and catalase (CAT) are immobilized in metal-organic frameworks by biomimetic mineralization to improve their stability via spatial confinement. The GOx can consume glucose, reduce ATP levels, and down-regulate the expression of heat shock proteins, which consequently sensitize tumor cells to indocyanine green-based photothermal therapy. Furthermore, the hydrogen peroxide generated by GOx as well as overexpressed in tumor can be decomposed by CAT and continuously generate oxygen, which further enhance the efficacy of oxygendependent starvation therapy and photodynamic therapy. The nanoreactors are directly delivered to the superficial tumor by microneedles, achieving efficient tumor accumulation and dramatically strengthened antitumor efficacy without obvious side effects, which provides a valuable paradigm for the application of cascade reaction-based combined therapy.
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