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

• 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
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c4nr07245f

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.