Mesoporous Nanoparticles for Targeted Drug Delivery
Functional mesoporous nanoparticles have recently attracted substantial attention in view of their great potential for targeted drug delivery and controlled release. For such demanding applications, it is desirable that the mesoporous particles be equipped with internal functionality for controlled host-guest interactions, a release system for the switchable release of the guest based on external stimuli, as well as targeting ligands for the required type of cell. We have developed a novel strategy to obtain control over the spatial localization of molecular functionality in such nanoparticles. This is achieved via synthesis of multiple core-shell colloidal mesoporous silica (CMS) nanoparticles having different molecular functionalities in the inner surface and on the outer particle shell. We show that active enzymes can be stabilized in such mesoporous nanoparticles using concepts of click-chemistry. In recent work, we have demonstrated a number of switchable release mechanisms based on changes in pH, redox potential, or activated by light. Our core-shell nanoparticles were also used for the successful release of bioactive molecules such as cell toxins into living cells. Microscopic studies shed light on the detailed entry and release mechanisms of these particles in living cells. This collaborative work is being performed with several LMU research groups in chemistry, physics and pharmacy.
- A Programmable DNA-Based Molecular Valve for Colloidal Mesoporous Silica: A. Schlossbauer, S. Warncke, P. M. E. Gramlich, J. Kecht, A. Manetto, T. Carell, T. Bein, Angew. Chem. Int. Ed. 2010, 49, 4734-4737.
A temperature-controlled valve system permits the targeted release of guest fluorescein molecules from the pores of colloidal mesoporous silica particles. The pore-opening temperature is dependent on the length of double-stranded DNA linkers. Avidin proteins that are joined to the DNA by a biotin modification act as the molecular valve at the exits to the pores.
- Role of Endosomal Escape for Disulfide-Based Drug Delivery from Colloidal Mesoporous Silica Evaluated by Live-Cell Imaging: A. M. Sauer, A. Schlossbauer, N. Ruthardt, V. Cauda, T. Bein, C. Bräuchle, Nano Lett. 2010, 10, 3684-3691.
Redox-driven intracellular disulfide-cleavage is a promising strategy to achieve stimuli-responsive and controlled drug release. We synthesized colloidal mesoporous silica (CMS) nanoparticles with ATTO633-labeled cysteine linked to the inner particle core via disulfide-bridges and characterized their cysteine release behavior after internalization into HuH7 cells by high-resolution fluorescence microscopy. Our study revealed that endosomal escape is a bottleneck for disulfide-linkage based drug release. Photochemical opening of the endosome leads to successful delivery of fluorescently labeled cysteine to the cytosol.
- Colchicine-Loaded Lipid Bilayer-Coated 50 nm Mesoporous Nanoparticles Efficiently Induce Microtubule Depolymerization upon Cell Uptake: V. Cauda, H. Engelke, A. Sauer, D. Arcizet, C. Bräuchle, J. Rädler, T. Bein, Nano Lett. 2010, 10, 2484-2492.
We report on a one-step assembly route where supported lipid bilayers (SLB) are deposited on functionalized colloidal mesoporous silica (CMS) nanoparticles, resulting in a core−shell hybrid system (SLB@CMS). The supported membrane acts as an intact barrier against the escape of encapsulated dye molecules. These stable SLB@CMS particles loaded with the anticancer drug colchicine are readily taken up by cells and lead to the depolymerization of microtubules with remarkably enhanced efficiency as compared to the same dose of drug in solution.
- Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica: A. Schlossbauer, J. Kecht, T. Bein, Angew. Chem. Int. Ed. 2009, 48, 3092-3095.
When avidin caps are attached to biotinylated colloidal mesoporous silica, the four subunits of the protein avidin can each bind to a biotin moiety attached to the surface (see picture). The resulting material is a promising candidate for the design of smart detergents or drug-delivery systems. The caps can be opened to release guest molecules by controlled enzymatic hydrolysis of the protein.