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Stepwise Degradable Nanocarriers Enabled Cascade Delivery for Synergistic Cancer Therapy

Citation

Yang, Y and Lu, Y and Abbaraju, PL and Azimi, I and Lei, C and Tang, J and Jambhrunkar, M and Fu, J and Zhang, M and Liu, Y and Liu, C and Yu, C, Stepwise Degradable Nanocarriers Enabled Cascade Delivery for Synergistic Cancer Therapy, Advanced Functional Materials ISSN 1616-301X (2018) [Refereed Article]

Copyright Statement

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

DOI: doi:10.1002/adfm.201800706

Abstract

Hypoxia-activated prodrugs have brought new opportunities for safe and effective tumor ablation, but their therapeutic efficacy is limited by insufficient activation in tumor microenvironments. Herein, a novel cascade delivery system with tandem functions by integrating a hypoxia-activated prodrug (AQ4N) and glucose oxidase (GOx) is designed to improve its efficacy. Innovative yolk–shell organosilica nanoparticles with a tetrasulfide bridged composition, a small-pore yolk, and a large-pore shell featuring a shell-to-yolk stepwise degradability are constructed as a carrier for AQ4N and GOx, one enzyme that catalyzes the oxidation of glucose to produce hydrogen peroxide. The glutathione (GSH) is depleted by tetrasulfide bond in the framework and induces shell degradation for fast release of GOx, which in turn induces starvation (glucose removal), oxidative cytotoxicity (H2O2 production and GSH depletion), and hypoxia (oxygen consumption). Finally, the hypoxia activates the liberated prodrug AQ4N for chemotherapy. The cascading and synergistic functions including GSH depletion, starvation, oxidative cytotoxicity, and chemotherapy lead to improved performance in tumor inhibition and antimetastasis.

Item Details

Item Type:Refereed Article
Keywords:nanoparticles, Cancer Therapy, Hypoxia‐activated prodrugs
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:126694
Year Published:2018
Web of Science® Times Cited:15
Deposited By:Pharmacy
Deposited On:2018-06-20
Last Modified:2019-01-07
Downloads:0

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