American Chemical Society
nn5034955_si_001.pdf (3.3 MB)

Ca2+-Dependent Intracellular Drug Delivery System Developed with “Raspberry-Type” Particles-on-a-Particle Comprising Mesoporous Silica Core and α‑Synuclein-Coated Gold Nanoparticles

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journal contribution
posted on 2014-09-23, 00:00 authored by Daekyun Lee, Je Won Hong, Chanyoung Park, Hagyeol Lee, Ji Eun Lee, Taeghwan Hyeon, Seung R. Paik
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 Ca2+. Intracellular uptake of the PoPs preloaded with doxorubicin as an anticancer drug and its subsequent Ca2+-dependent release were demonstrated with HeLa cells in the presence of intracellular Ca2+-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.