Journal
NANOSCALE
Volume 7, Issue 17, Pages 7953-7964Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4nr07245f
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB 749]
- Excellence Clusters Nanosystems Initiative Munich (NIM)
- Center for Integrated Protein Science Munich (CIPSM)
- Verein der Chemischen Industrie (VCI)
- Romer Stiftung
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A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.
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