Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery

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-vinylpyrid...

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Bibliographic Details
Published in:Nanoscale 2015-05, Vol.7 (17), p.7953-7964
Main Authors: Niedermayer, Stefan, Weiss, Veronika, Herrmann, Annika, Schmidt, Alexandra, Datz, Stefan, Müller, Katharina, Wagner, Ernst, Bein, Thomas, Bräuchle, Christoph
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Cell Survival - drug effects
Covalence
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Drug delivery systems
Drugs
Fluorescent Dyes - chemistry
Fluorescent Dyes - pharmacokinetics
HeLa Cells
Humans
Hydrogen-Ion Concentration
KB Cells
Modular
Nanoparticles
Nanoparticles - chemistry
Nanostructure
Platforms
Polyethylene Glycols - chemistry
Polyethylene Glycols - pharmacokinetics
Polyvinyls - chemistry
Polyvinyls - pharmacokinetics
Silicon dioxide
Silicon Dioxide - chemistry
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Summary: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.
ISSN:2040-3364
2040-3372
DOI:10.1039/c4nr07245f