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

• Published in: ACS nano Vol. 8; no. 9; pp. 8887 - 8895
• Main Authors: Lee, Daekyun, Hong, Je Won, Park, Chanyoung, Lee, Hagyeol, Lee, Ji Eun, Hyeon, Taeghwan, Paik, Seung R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 23.09.2014
• Subjects: alpha-Synuclein - chemistry; Calcium - metabolism; Doxorubicin - chemistry; Doxorubicin - metabolism; Drug Carriers - chemistry; Gold - chemistry; HeLa Cells; Humans; Intracellular Space - metabolism; Metal Nanoparticles - chemistry; Porosity; Silicon Dioxide - chemistry; particles-on-a-particle; controlled release; mesoporous silica nanoparticle; drug delivery; α-synuclein
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/nn5034955

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.