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Polymers 2018, 10(4), 390; https://doi.org/10.3390/polym10040390

Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery

1
School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea
2
Department of Physics and Applied Mathematics, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad 45650, Pakistan
3
Department of Material Engineering, Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad 45650, Pakistan
4
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 20 February 2018 / Revised: 27 March 2018 / Accepted: 28 March 2018 / Published: 1 April 2018
(This article belongs to the Special Issue Polymeric Micro/Nanoparticles for Bio-Medical Applications)
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Abstract

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state. Under hypoxic conditions, the release rate of doxorubicin (DOX) from DOX-loaded CD-HR-MSNs (DOX-CD-HR-MSNs) increased along with the disintegration of the gatekeeper. Conversely, DOX release was retarded under normoxic conditions. In vitro experiments confirmed that DOX-CD-HR-MSNs exhibit higher toxicity to hypoxic cells when compared to normoxic cells. Confocal microscopy images indicated that DOX-CD-HR-MSNs effectively release DOX into SCC-7 cells under hypoxic conditions. These results demonstrate that CD-HR-MSNs can release drugs in a hypoxia-responsive manner, and thus are promising drug carriers for hypoxia-targeted cancer therapy. View Full-Text
Keywords: hypoxia; mesoporous silica nanoparticles; nitroimidazole; β-cyclodextrin; doxorubicin hypoxia; mesoporous silica nanoparticles; nitroimidazole; β-cyclodextrin; doxorubicin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Khatoon, S.; Han, H.S.; Jeon, J.; Rao, N.V.; Jeong, D.-W.; Ikram, M.; Yasin, T.; Yi, G.-R.; Park, J.H. Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery. Polymers 2018, 10, 390.

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