Stimulus-Responsive Controlled Release System by Covalent Immobilization of an Enzyme into Mesoporous Silica Nanoparticles
journal contributionposted on 18.04.2012, 00:00 by Jessica Méndez, Alina Monteagudo, Kai Griebenow
Mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug delivery carriers for therapeutic agents. Herein, we explored the covalent immobilization of proteins into MSN to generate a stimulus-responsive controlled release system. First, MSN were functionalized with thiol groups using (mercaptopropyl)-trimethoxysilane (MPTMS). Functionalization was verified by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering. The model enzyme carbonic anhydrase (CA) was coupled to sulfosuccinimidyl 6-[3′(2-pyridyldithio)-propionamido]hexanoate (Sulfo-LC-SPDP) at a low ratio of 1:1 to prevent enzyme inactivation and subsequently covalently immobilized into MSN via thiol–disulfide interchange. The enzyme could be released from MSN with 10 mM glutathione, which represents intracellular redox conditions, while it remained bound to the MSN at extracellular redox conditions represented by 1 μM glutathione. The activity of the released enzyme was >80% demonstrating that the enzyme was still largely functional and active after immobilization and release. Human cervical cancer (HeLa) cells were incubated with the MSN–CA bioconjugates at various concentrations for 24 h and the data show good biocompatibility. In summary, we demonstrate the potential of MSN as drug delivery systems for proteins.
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model enzyme carbonic anhydraseXPSextracellular redox conditionsMesoporous Silica NanoparticlesMesoporous silica nanoparticlesMPTMScovalent immobilizationenzyme inactivationFTIR10 mM glutathioneCAintracellular redox conditionsrelease systemthiol groupsMSNdrug delivery carriers1 μ M glutathione24 hCovalent Immobilizationdrug delivery systemsdata show