title: Highly efficient siRNA delivery from core-shell mesoporous silica nanoparticles with multifunctional polymer caps.
abstract: A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well.
authors.affiliation: Department of Chemistry and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Möller
authors.affiliation: Pharmaceutical Biotechnology and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. ernst.wagner@cup.uni-muenchen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Müller
authors.affiliation: Department of Chemistry and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelke
authors.affiliation: Department of Chemistry and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bräuchle
authors.affiliation: Pharmaceutical Biotechnology and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. ernst.wagner@cup.uni-muenchen.de.
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Chemistry and Center for NanoScience, University of Munich (LMU), Butenandtstrasse 5-13, 81377 Munich, Germany. bein@lmu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bein
mesh_terms: D000327:Adsorption; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D016521:Electrophoresis, Gel, Pulsed-Field; D005456:Fluorescent Dyes / Q000737:chemistry; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry*; D014162:Transfection
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D011108:Polymers; D034741:RNA, Small Interfering; C085321:cyanine dye 5; D012822:Silicon Dioxide; D008156:Luciferases