Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 167, Issue -, Pages 407-414Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.colsurfb.2018.04.038
Keywords
Stepwise-acid-active; Mesoporous silica nanoparticle; Controlled release; Cancer therapy; pH-sensitivity
Funding
- National Natural Science Foundation of China [51773055, 51503060, 31401498]
- Wuhan Morning Light Plan of Youth Science and Technology [2017050304010283]
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Due to the difference of pH values between normal tissues, tumor tissues and intracellular environments, DOX@MSN-CD-PEG, a stepwise-acid-active organic/inorganic hybrid drug delivery system (DDS) was reported in this article. The inorganic mesoporous silica nanoparticle (MSN) was introduced for loading of doxorubicin hydrochloride (DOX). Then organic components were applied to achieve the stepwise-acid-active intracellular drug release: MSN was capped with a beta-cyclodextrine (beta-CD) based host-guest system via pH-sensitive epoxy bond. Then PEG was grafted outside of the carriers through pH-sensitive benzoic imine bond. With the protection of PEG layer, the carriers were difficult cellular uptake by normal cells but could be acid-activated for cytophagy by cancer cells in the slightly acidic environments in tumor tissues because of the abscission of PEG. Inside the cells, the more acidic environments could further activate the carriers to release DOX as the leaving of the host-guest system. The fabrication processes of DOX@MSN-CD-PEG were monitored. And the stepwise-acid-active property of which was investigated by acid-triggered PEG abscission studies and in vitro drug release studies at pH 7.4 and 6.5, respectively. The in vitro cellular cytotoxicity and cellular uptake behavior were also investigated. In summary, the stepwise-acid-active hybrid DDS should be considerable for cancer therapy. (C) 2018 Elsevier B.V. All rights reserved.
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