title: Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release.
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.
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Datz
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Argyo
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Gattner
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weiss
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brunner
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bretzler
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Schirnding
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Adriano A
authors.initials: AA
authors.lastname: Torrano
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Fabio
authors.initials: F
authors.lastname: Spada
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Vrabel
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelke
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bräuchle
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carell
authors.affiliation: Department of Chemistry, Nanosystems Initiative Munich (NIM), Center for Nano Science (CeNS), and Center for Integrated Protein Science Munich (CIPSM), University of Munich (LMU), Butenandtstr. 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bein
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003609:Dactinomycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D015202:Protein Engineering; D011955:Receptors, Drug / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D011955:Receptors, Drug; D003609:Dactinomycin; D012822:Silicon Dioxide; D024402:Carbonic Anhydrase II