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Enzyme-Induced and Tumor-Targeted Drug Delivery System Based on Multifunctional Mesoporous Silica Nanoparticles
journal contribution
posted on 2015-05-06, 00:00 authored by Yin-Jia Cheng, Guo-Feng Luo, Jing-Yi Zhu, Xiao-Ding Xu, Xuan Zeng, Dong-Bing Cheng, You-Mei Li, Yan Wu, Xian-Zheng Zhang, Ren-Xi Zhuo, Feng HeFunctional
mesoporous silica particles have attracted growing research
interest for controlled drug delivery in targeted cancer therapy.
For the purpose of efficient targeting tumor cells and reducing the
adverse effect of antitumor drug doxorubicin (DOX), biocompatible
and enzyme-responsive mesoporous silica nanoparticles (MSNs) with
tumor specificity were desired. To construct these functional MSNs,
the classic rotaxane structure formed between alkoxysilane tether
and α-cyclodextrin (α-CD) was employed to anchor onto
the orifices of MSNs as gatekeeper in this work. After subsequent
modification by multifunctional peptide (azido-GFLGR7RGDS
with tumor-targeting, membrane-penetrating, and cathepsin B-responsive
functions) to stabilize the gatekeeper, the resulting functional MSNs
showed a strong ability to load and seal DOX in their nanopores. When
incubating these DOX-loaded MSNs with tumor and normal cells, the
nanoparticles could efficiently employ their surface-encoded RGDS
and continuous seven arginine (R7) sequences to target
tumor cells, penetrate the cell membrane, and enter tumor cells. Because
cathepsin B overexpressed in late endosomes and lysosomes of tumor
cells could specifically hydrolyze GFLG sequences of the nanovalves,
the DOX-loaded MSNs showed an “off-on” drug release
behavior that ∼80% loaded DOX could be released within 24 h
and thus showed a high rate of apoptosis. Furthermore, in vitro cellular
experiments indicated that DOX-loaded MSNs (DOX@MSN-GFLGR7RGDS/α-CD) had high growth inhibition toward αvβ3-positive HeLa cancerous cells. The research might
offer a practical way for designing the tumor-targeted and enzyme-induced
drug delivery system for cancer therapy.