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arXiv · 1510.03649

Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

Stefan Datz·Christian Argyo·Michael Gattner·Veronika Weiss·Korbinian Brunner·Johanna Bretzler·Constantin von Schirnding·Fabio Spada·Hanna Engelke·Milan Vrabel·Christoph Bräuchle·Thomas Carell·Thomas Bein
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Abstract

Effective and controlled drug delivery systems with on-demand release and targeting abilities have received enormous attention for biomedical applications. Here, we describe a novel enzyme-based cap system for mesoporous silica nanoparticles (MSNs) that is directly combined with a targeting ligand via bio-orthogonal click chemistry. The capping system is based on the pH-responsive binding of an aryl-sulfonamide-functionalized MSN and the enzyme carbonic anhydrase (CA). An unnatural amino acid (UAA) containing a norbornene moiety was genetically incorporated into CA. This UAA allowed for the site-specific bio-orthogonal attachment of even very sensitive targeting ligands such as folic acid and anandamide. This leads to specific receptor-mediated cell and stem cell uptake. We demonstrate the successful delivery and release of the chemotherapeutic agent Actinomycin D to KB cells. This novel nanocarrier concept provides a promising platform for the development of precisely controllable and highly modular theranostic systems.

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Stefan Datz, Christian Argyo, Michael Gattner, Veronika Weiss, Korbinian Brunner, Johanna Bretzler, Constantin von Schirnding, Fabio Spada, Hanna Engelke, Milan Vrabel, Christoph Bräuchle, Thomas Carell, Thomas Bein. 2015-10-13. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release. https://doi.org/10.1039/c5nr08163g

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