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

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+)…