title: A mesoporous nanocontainer gated by a stimuli-responsive peptide for selective triggering of intracellular drug release.
abstract: Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers have great potential for effective delivery of cargo molecules to the desired sites. For that purpose, peptides could be effective candidates as gatekeepers because of their bioresponsiveness and targeting capability. Taking advantage of the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive conformational conversion and the steric bulkiness of the tryptophan unit. The turn structure induced by an intramolecular disulfide bond of the peptide gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione (GSH), the peptide conformation was converted to a random structure, which opened the orifice of the mesopore leading to the release of DOX. The amine moiety of the lysine of the peptide gatekeeper was PEGylated to enhance dispersion stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX in A549 human lung cancer cells in a controlled manner triggered by intracellular GSH, but not in CCD normal lung cells containing a low intracellular GSH level. In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher cytotoxicity induced by apoptosis than that in CCD cells.
authors.affiliation: Department of Polymer Science and Engineering, Inha University, Incheon 402-751, Korea. chk@inha.ac.kr.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, School of Medicine, Inha University, Incheon 402-751, Korea.
authors.forename: Eun-Taex
authors.initials: ET
authors.lastname: Oh
authors.affiliation: Department of Polymer Science and Engineering, Inha University, Incheon 402-751, Korea. chk@inha.ac.kr.
authors.forename: Haerry
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Polymer Science and Engineering, Inha University, Incheon 402-751, Korea. chk@inha.ac.kr.
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 402-751, Korea. park001@inha.ac.kr.
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Polymer Science and Engineering, Inha University, Incheon 402-751, Korea. chk@inha.ac.kr.
authors.forename: Chulhee
authors.initials: C
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation; D012822:Silicon Dioxide
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D053769:Nanocapsules; D009842:Oligopeptides; D012822:Silicon Dioxide; D004317:Doxorubicin