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Functionalized silicon quantum dots tailored for targeted siRNA delivery |
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| Authors: | S. Klein M.F. Fromm W. Neuhuber |
| Affiliation: | a Department Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen, Germany b Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander University of Erlangen-Nuremberg, Fahrstr. 17, D-91054 Erlangen, Germany c Institute of Anatomy I, Friedrich-Alexander University of Erlangen-Nuremberg, Krankenhausstr. 9, D-91054 Erlangen, Germany d Departments of Anatomy/Ophthalmology, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria |
| Abstract: | For RNA interference (RNAi) mediated silencing of the ABCB1 gene in Caco-2 cells biocompatible luminescent silicon quantum dots (SiQDs) were developed to serve as self-tracking transfection tool for ABCB1 siRNA. While the 2-3 nm sized SiQD core exhibits green luminescence, the QD surfaces are completely saturated with covalently linked 2-vinylpyridine that may electrostatically bind siRNA. For down-regulating P-glycoprotein (Pgp) expression of the ABCB1 gene the SiQDs were complexed with siRNA. The cellular uptake and allocation of SiQD-siRNA complexes in Caco-2 cells were monitored using confocal laser scanning microscopy and transmission electron microscopy. The release of siRNA to the cytoplasm was verified through real-time PCR quantification of the reduced ABCB1 mRNA level. Additional evidence was obtained from time-resolved in situ fluorescence spectroscopic monitoring of the Pgp efflux dynamics in transfected Caco-2 cells which yielded significantly reduced transporter efficiencies for the Pgp substrate Rhodamine 123. |
| Keywords: | Silicon quantum dots siRNA delivery MDR1 P-glycoprotein Caco-2 cells |
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