Glucose oxidase loaded Cu 2+ based metal-organic framework for glutathione depletion/reactive oxygen species elevation enhanced chemotherapy.

Autor: Xu J; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China., Xu Y; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: zhangtong_hmu60@163.com., Sun L; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China., Lu B; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China., Yan X; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China., Wang Z; Department of Thoracic Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China., Zhang T; Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: zhangtong_hmu60@163.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Sep; Vol. 141, pp. 111606. Date of Electronic Publication: 2021 Jun 18.
DOI: 10.1016/j.biopha.2021.111606
Abstrakt: Introduction: The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine.
Methods: Here in our study, a Cu 2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers.
Results: Our results showed that the GOx can catalyze glucose and produce H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance.
Discussion: The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
(Copyright © 2021. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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