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Ca2+-Dependent Intracellular Drug Delivery System Developed with 鈥淩aspberry-Type鈥?Particles-on-a-Particle Comprising Mesoporous Silica Core and 伪-Synuclein-Coated Gold Nanoparticles
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文摘
For the development of an intracellular cargo release system with mesoporous silica nanoparticles (MSN), gold nanoparticles coated with an amyloidogenic protein of 伪-synuclein were employed to prepare a protein-mediated nanocomposite into the 鈥渞aspberry-type鈥?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 伪-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 伪-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 伪-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.r>

Keywords:

伪-synuclein; controlled release; drug delivery; mesoporous silica nanoparticle; particles-on-a-particle

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