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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 |
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Keywords: | nanoparticles, Cancer Therapy, Hypoxia‐activated prodrugs |
Research Division: | Biomedical and Clinical 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: | 65 |
Deposited By: | Pharmacy |
Deposited On: | 2018-06-20 |
Last Modified: | 2019-01-07 |
Downloads: | 0 |
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