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Title: Redox-responsive mesoporous silica nanoparticles : a physiologically sensitive codelivery vehicle for siRNA and doxorubicin
Authors: Ma, Xing
Teh, Cathleen
Zhang, Quan
Borah, Parijat
Choong, Cleo Swee Neo
Korzh, Vladimir
Zhao, Yanli
Keywords: DRNTU::Science::Medicine
Issue Date: 2014
Source: Ma, X., Teh, C., Zhang, Q., Borah, P., Choong, C. S. N., Korzh, V., et al. (2014). Redox-responsive mesoporous silica nanoparticles : a physiologically sensitive codelivery vehicle for siRNA and doxorubicin. Antioxidants & redox signaling, 21(5), 707-722.
Series/Report no.: Antioxidants & redox signaling
Abstract: Aims: Efficient siRNA/drug codelivery carriers can offer great promises to cancer treatment on account of synergistic effect provided from cancer-associated gene and anticancer drugs. In this work, a redox-responsive drug/siRNA codelivery vehicle based on mesoporous silica nanoparticles was fabricated to simultaneously deliver siRNA and doxorubicin (Dox) in vitro and in vivo. Results: The nanoparticle surface was functionalized with the adamantane (AD) units. Formation of stable host–guest complex between disulfide bond linked-AD and ethylenediamine-modified β-cyclodextrin is capable of fully blocking drugs inside the nanopores, while amino groups can complex with siRNA via electrostatic interaction. Relatively high concentration of glutathione in biophysical environment provides natural reducing agent to trigger drug/siRNA release by cleaving pre-introduced disulfide bonds. B-cell lymphoma 2 (Bcl-2) siRNA was codelivered to silence Bcl-2 protein expression in HeLa cells, resulting in enhanced chemotherapy efficacy in vitro. In vivo delivery experiment carried out in transgenic zebrafish larvae indicates that the delivery of Dox inhibits the development of choroid plexus in a dose-dependent manner, leading to successful decrease of green fluorescence protein transcription in choroid plexus. Reduction of liver tumor was also demonstrated after injection of Dox-loaded nanoparticles. Innovation: We successfully demonstrated that functional nanoparticles could serve as an efficient carrier for the delivery of Bcl-2 siRNA and Dox in HeLa cells and in transgenic zebrafish larvae, leading to enhanced therapeutic efficacy. Conclusion: Enhanced cytotoxicity caused by simultaneous delivery of Bcl-2 siRNA and Dox was observed in HeLa cells. Drug-loaded nanoparticles were internalized in vivo, inhibiting the development of choroid plexus and the progression of liver tumor.
ISSN: 1523-0864
DOI: 10.1089/ars.2012.5076
Rights: © 2014 Mary Ann Liebert. This paper was published in Antioxidants & Redox Signaling and is made available as an electronic reprint (preprint) with permission of Mary Ann Liebert. The paper can be found at the following official DOI: [].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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