A pH-sensitive stimulus-response system for controlled drug release was prepared by modifying nanoporous silica nanoparticles (NPSNPs) with poly(4-vinylpyridine) using a bismaleimide as linker. At physiological pH values, the polymer serves as gate keeper blocking the pore openings to prevent the release of cargo molecules. At acidic pH values as they can occur during a bacterial infection, the polymer strains become protonated and straighten up due to electrostatic repulsion. The pores are opened and the cargo is released. The drug chlorhexidine was loaded into the pores because of its excellent antibacterial properties and low tendency to form resistances. The release was performed in PBS and diluted hydrochloric acid, respectively. The results showed a considerably higher release in acidic media compared to neutral solvents. Reversibility of this pH-dependent release was established. In vitro tests proved good cytocompatibility of the prepared nanoparticles. Antibacterial activity tests with Streptococcus mutans and Staphylococcus aureus revealed promising perspectives of the release system for biofilm prevention. The developed polymer-modified silica nanoparticles can serve as an efficient controlled drug release system for long-term delivery in biomedical applications, such as in treatment of biofilm-associated infections, and could, for example, be used as medical implant coating or as components in dental composite materials
