Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 33, Issue 6, Pages 3426-3431Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.msec.2013.04.033
Keywords
Reduction responsive; Mesoporous silica nanoparticle; Drug delivery; Core-shell structure; Disulfide bond
Categories
Funding
- National Natural Science Foundation of China [51073042, 51103026]
- Shanghai Natural Science Funds [11ZR1403100]
- Shanghai Scientific and Technological Innovation Project [11JC1400600, 124119a2400]
- Shanghai Rising-Star Program [12QB1402900]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110071120006]
- Shanghai Bureau of Health [20124097]
- The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education, China
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A novel reduction-responsive drug delivery system was successfully constructed with mesoporous silica nanoparticle (MSN) core as a drug carrier and poly(acrylic acid) (PAA) shell crosslinked by disulfide linkages as a drug release switcher. To keep the pore structure of MSN intact, PAA was covalently attached to the exterior surface of MSN before removing structure-template via radical polymerization. After removing structure-template and loading doxorubicin (DOX), the PAA shell was crosslinked by cystamine dihydrochloride through amidation reaction. The loading content and the entrapment efficiency of DOX could reach up to 40.2% and 80.4%, respectively. Because that the dissociation of disulfide linkage is reduction-responsive, the release behavior of DOX could be controlled by varying the concentration of reductant, and the release rate was 49.4% after 24 h with the existence of 2 mM glutathione (simulated environment of cancer cells), about three times higher than that of without glutathione (corresponding to normal human cells), which was only 16.9%. The in vitro cell assays demonstrated that the disulfide linkages crosslinked MSN-PAA (MSN-PM-crosslinked) was highly biocompatible and suitable to use as drug carrier, and the DOX loaded MSN-PAA-crosslinked showed remarkable cytotoxicity to HeLa cells (human cancer cells), and relatively lower cytotoxicity to 293 cells (human normal cells). These results imply that the MSN-PAA-crosslinked is a promising platform to construct reduction-responsive controlled drug delivery system for cancer therapy. (c) 2013 Elsevier B.V. All rights reserved.
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