Super-Resolution Imaging of Spatial Heterogeneities in Model Thermosensitive Hydrogels with Implications for Their Origins

Three-dimensional nanoscale cross-link density variations are an important and incompletely understood morphological aspect of polymer gels. Here, within the context of establishing a deeper understanding of these so-called spatial heterogeneities, we study the spatial distribution of dye-tagged acrylamide monomers in bulk thermosensitive PNIPAM gels using a combination of 3D STED and multicolor confocal microscopy. We identify consistent microstructural trends for the various dye-tagged monomers, thereby expanding the prevailing picture of spatial heterogeneities in thermosensitive gels. Specifically, we provide new morphological insights into the distribution of cross-links, the nature of the interface that defines the polymer-rich regions, and the incidence and connectivity of higher cross-link density regions as a function of quench time and preparation temperature. While phase separation and reactivity rate constant differences have only been studied in isolation as the dominant cause of spatial heterogeneities in thermosensitive gels, our results show that both phenomena play an important role in determining cross-link density distributions

Inclusion of Quercetin in Gold Nanoparticles Decorated with Supramolecular Hosts Amplifies Its Tumor Targeting Properties

Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential, we developed a nanohybrid delivery platform with a noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulfonatocalix­[4]­arene, enabling a 62 000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in an acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate noncovalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50-fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetin-loaded nanoparticles altered the expression of 27 genes related to apoptosis