Hollow, pH-Sensitive Microgels as Nanocontainers for the Encapsulation of Proteins

Depending on their architectural and chemical design, microgels can selectively take up and release small molecules by changing the environmental properties, or capture and protect their cargo from the surrounding conditions. These outstanding properties make them promising candidates for use in biomedical applications as delivery or carrier systems. In this study, hollow anionic p(N-isopropylacrylamid-e-co-itaconic acid) microgels are synthesized and analyzed regarding their size, charge, and charge distribution. Furthermore, interactions between these microgels and the model protein cytochrome c are investigated as a function of pH. In this system, pH serves as a switch for the electrostatic interactions to alternate between no interaction, attraction, and repulsion. UV-vis spectroscopy is used to quantitatively study the encapsulation of cytochrome c and possible leakage. Additionally, fluorescence-lifetime images unravel the spatial distribution of the protein within the hollow microgels as a function of pH. These analyses show that cytochrome c mainly remains entrapped in the microgel, with pH controlling the localization of the protein - either in the microgel's cavity or in its network. This significantly differentiates these hollow microgels from microgels with similar chemical composition but without a solvent filled cavity.