title: Reduction-responsive drug delivery based on mesoporous silica nanoparticle core with crosslinked poly(acrylic acid) shell.
abstract: 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 24h 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-PAA-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.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, PR China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Li
authors.forename: Jin Zhong
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hu
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; C006903:carbopol 940; D012822:Silicon Dioxide; D004317:Doxorubicin