(408a) Stimulus-Responsive Controlled Release System by Covalent Immobilization of Proteins Into Mesoporous Silica Nanoparticles

Modern treatment options in cancer and other therapies increasingly rely on passive and active targeting of the drug. In this context, mesoporous silica nanoparticles (MSN) have emerged as an attractive class of drug delivery carriers for therapeutic agents. We recently explored the covalent immobilization of model proteins into MSN to generate stimulus-responsive controlled release systems. The model proteins carbonic anhydrase (CA) and cytochrome c (Cyt-c) were coupled to sulfosuccinimidyl 6-[3’(2-pyridyldithio)-propionamido]hexanoate (Sulfo-LC-SPDP) and subsequently covalently immobilized into MSN via thiol-disulfide interchange. The model proteins could be released from MSN with 10 mM glutathione which represents intra-cellular redox conditions while it remained bound to the MSN at extra-cellular redox conditions represented by 1 µM glutathione. Bioactivity of the model proteins was maintained well during immobilization and release. Studies using human cervical cancer (HeLa) cells showed good biocompatibility. MSN containing immobilized Cyt-c induced apoptosis in HeLa cells. We will also highlight recent data on endocytosis of Cyt-c loaded MSN and endosomal escape obtained by confocal microscopy. Furthermore, we will present data on active targeting using MSN by binding of of suitable ligands.