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Stepwise Degradable Nanocarriers Enabled Cascade Delivery for Synergistic Cancer Therapy

Yang, Yannan, Lu, Y, Abbaraju, PL, Azimi, I ORCID: 0000-0001-9477-9999, Lei, C, Tang, J, Jambhrunkar, M, Fu, J, Zhang, M, Liu, Y, Liu, C and Yu, C 2018 , 'Stepwise Degradable Nanocarriers Enabled Cascade Delivery for Synergistic Cancer Therapy' , Advanced Functional Materials , doi: 10.1002/adfm.201800706.

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Abstract

Hypoxia-activated prodrugs have brought new opportunities for safe andeffective tumor ablation, but their therapeutic efficacy is limited by insufficientactivation in tumor microenvironments. Herein, a novel cascade deliverysystem with tandem functions by integrating a hypoxia-activated prodrug(AQ4N) and glucose oxidase (GOx) is designed to improve its efficacy. Innovativeyolk–shell organosilica nanoparticles with a tetrasulfide bridged composition,a small-pore yolk, and a large-pore shell featuring a shell-to-yolk stepwisedegradability are constructed as a carrier for AQ4N and GOx, one enzyme thatcatalyzes the oxidation of glucose to produce hydrogen peroxide. The glutathione(GSH) is depleted by tetrasulfide bond in the framework and inducesshell degradation for fast release of GOx, which in turn induces starvation (glucoseremoval), oxidative cytotoxicity (H2O2 production and GSH depletion),and hypoxia (oxygen consumption). Finally, the hypoxia activates the liberatedprodrug AQ4N for chemotherapy. The cascading and synergistic functionsincluding GSH depletion, starvation, oxidative cytotoxicity, and chemotherapylead to improved performance in tumor inhibition and antimetastasis.

Item Type: Article
Authors/Creators:Yang, Yannan 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
Keywords: nanoparticles, Cancer Therapy, Hypoxia‐activated prodrugs
Journal or Publication Title: Advanced Functional Materials
Publisher: Wiley-V C H Verlag Gmbh
ISSN: 1616-301X
DOI / ID Number: 10.1002/adfm.201800706
Copyright Information:

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

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