title: Ca2+-dependent intracellular drug delivery system developed with "raspberry-type" particles-on-a-particle comprising mesoporous silica core and α-synuclein-coated gold nanoparticles.
abstract: For the development of an intracellular cargo release system with mesoporous silica nanoparticles (MSN), gold nanoparticles coated with an amyloidogenic protein of α-synuclein were employed to prepare a protein-mediated nanocomposite into the "raspberry-type" particles-on-a-particle (PoP). The PoPs were successfully fabricated only at pH 4.4 by yielding the MSN coverage to 75.3% with 5 nm gold nanoparticles covalently coated with a mutant form of α-synuclein containing a cysteine residue at the C-terminus. The entrapped cargo of rhodamine 6G was shown to be selectively released from PoPs upon exposure to divalent cations including the α-synuclein-specific pathophysiological ligand of Ca(2+). Intracellular uptake of the PoPs preloaded with doxorubicin as an anticancer drug and its subsequent Ca(2+)-dependent release were demonstrated with HeLa cells in the presence of intracellular Ca(2+)-regulating agents. Therefore, the fabrication of PoPs with the self-interactive protein of α-synuclein is expected to serve as a platform technology for preparation of diversified nanocomposites with various nanoparticles and/or bioactive molecules for eventual applications in the areas of theranostics.
authors.affiliation: School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University , Seoul 151-744, Republic of Korea.
authors.forename: Daekyun
authors.initials: D
authors.lastname: Lee
authors.forename: Je Won
authors.initials: JW
authors.lastname: Hong
authors.forename: Chanyoung
authors.initials: C
authors.lastname: Park
authors.forename: Hagyeol
authors.initials: H
authors.lastname: Lee
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Taeghwan
authors.initials: T
authors.lastname: Hyeon
authors.forename: Seung R
authors.initials: SR
authors.lastname: Paik
mesh_terms: D002118:Calcium / Q000378:metabolism*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D051844:alpha-Synuclein; D006046:Gold; D012822:Silicon Dioxide; D004317:Doxorubicin; D002118:Calcium
keywords: controlled release; drug delivery; mesoporous silica nanoparticle; particles-on-a-particle; α-synuclein